Organic Electrochemistry

1
1
Methods to Investigate
Mechanisms of Electroorganic
Reactions
Bernd Speiser
.. ..
Institut f ur Organische Chemie, Auf der Morgenstelle 18, T ubingen, Germany
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.1.1 Scope: Methods of Molecular Electrochemistry . . . . . . . . . . . . . . . 3
1.1.2 Historical Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2 Why and How to Investigate Mechanisms of Electroorganic Reactions 4

1.2.1 Steps of Electrode Reaction Mechanisms . . . . . . . . . . . . . . . . . . . 4
1.2.1.1 General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.2.1.2 Transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.2.1.3 Electron Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.2.1.4 Chemical Kinetic Steps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.2.1.5 Adsorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.2.2 Organic Electrode Reaction Mechanisms . . . . . . . . . . . . . . . . . . . 6
1.2.2.1 Electron Transfer Initiates Chemistry . . . . . . . . . . . . . . . . . . . . . 6
1.2.2.2 Nomenclature of Electrode Reaction Mechanisms . . . . . . . . . . . . . 6
1.2.3 Formal Description of Events at an Electrode . . . . . . . . . . . . . . . . 7
1.2.3.1 Current-Potential-Time Relationships . . . . . . . . . . . . . . . . . . . . . 7
1.2.3.2 Concentration Profiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.2.4 Methods of Mechanistic Electroorganic Chemistry . . . . . . . . . . . . 7
1.2.4.1 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.2.4.2 Controlled-Potential Techniques . . . . . . . . . . . . . . . . . . . . . . . . 7
1.2.4.3 Controlled-Current Techniques . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.2.4.4 Hydrodynamic Voltammetry . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.2.4.5 Exhaustive Electrolysis Techniques . . . . . . . . . . . . . . . . . . . . . . . 13
1.3 How to Gain Access to Kinetics, Thermodynamics, and Mechanisms

of Electroorganic Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
1.3.1 Qualitative and Quantitative Investigation of Electrode Reaction
Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
1.3.2 General Recommendations for Mechanistic Analysis . . . . . . . . . . . 14
2 1 Methods to Investigate Mechanisms of Electroorganic Reactions
1.3.3 Some Mechanistic Examples . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

1.3.3.1 Pure ET Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
1.3.3.2 Follow-up Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
1.3.3.3 Preequilibria to ETs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.3.3.4 Catalytic Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.4 How to Gain Additional Information about Electroorganic Reaction

Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
1.4.1 Simulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
1.4.2 Ultramicroelectrodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
1.4.3 Electrogravimetry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
1.4.4 Spectroelectrochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
1.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
3
1.1 molecular electrochemistry [1] or dynamic

Introduction electrochemistry [2] have been used for that
part of electrochemistry that studies the
1.1.1
mechanistic events at or near an electrode
Scope: Methods of Molecular
on a molecular level.
Electrochemistry
There are a large number of methods
(often also called electroanalytical methods)
Reaction mechanisms divide the transfor-
for such studies of which only the most
mations between organic molecules into
important ones can be covered in this
classes that can be understood by well-
chapter. Moreover, technical details of
defined concepts. Thus, for example, the
the methods cannot be described, and
SN 1 or SN 2 nucleophilic substitutions are
emphasis will be placed on their use in
examples of organic reaction mechanisms. mechanistic electroorganic chemistry.
Each mechanism is characterized by tran-
sition states and intermediates that are
1.1.2
passed over while the reaction proceeds. Historical Development
It defines the kinetic, stereochemical, and
product features of the reaction. Reaction Although organic electrochemistry had
mechanisms are thus extremely important already been established in the nineteenth
to optimize the respective conversion for century, only the 1960s saw the advent
conditions, selectivity, or yields of desired of detailed electroorganic mechanistic
products. studies.
Reaction mechanisms are also defined Most of the techniques employed can be
for electroorganic reactions, induced by traced back to polarography, which was al-
or including an electron transfer at an ready in use in 1925, to determine the
electrode. Knowledge of such electrode concentrations of organic molecules [3].
reaction mechanisms includes, prefer- Technical developments in instrumenta-
ably but not exclusively, the potential at tion (potentiostats) [4], the use of nonaque-
which the reaction proceeds, the proof ous electrolytes [5], and the digital control
of intermediates, the electron stoichiom- of experiments [6] led to the spread of
etry, the kinetics of the various reaction electroanalytical techniques. For example,
steps, and the transport properties of cyclic voltammograms are frequently and
the species involved. Recently, the terms routinely used today to define the redox
properties of newly synthesized organic (substrate) from the bulk of the electrolyte
compounds similar to the use of NMR to the electrode plays an important, often
spectra for structural characterization. rate-determining role. The electron trans-
Numerical simulation of the experi- fer step occurs at the interface. The product
ments [7] became increasingly available of the redox reaction is transported back
during the 1980s, and ultramicroelec- to the bulk. Purely chemical reactions may
trodes [8] opened the way not only to precede or follow these steps. Specific in-
ever-faster timescales but also to finer teractions of any species present in the
lateral resolution when characterizing elec- electrolyte with the electrode surface leads
trode processes. Finally, combinations to adsorption, which may considerably in-
with spectroscopic and mass-sensitive de- fluence the overall process.
vices opened new ways to augment infor-
mation available from molecular electro-
1.2.1.2 Transport
chemical experiments.
Three types of mass transport are impor-
This development contributes to a still-
tant at an electrode:
increasing body of knowledge about the
fate of organic molecules upon oxidation 1. Diffusion (along a concentration gradi-
and reduction. ent) is observed if the solution near the
electrode is depleted from a substrate or
a product is accumulated. Diffusion is
1.2 characterized by a diffusion coefficient
Why and How to Investigate Mechanisms
D (typical value: 10−5 cm2 /s) and ex-
of Electroorganic Reactions
tends over a diffusion layer (thickness:
1.2.1 δ) that develops from the electrode into
Steps of Electrode Reaction Mechanisms the electrolyte. At the outward bound-
ary the concentrations approach their
1.2.1.1 General bulk values.
As heterogeneous reactions at the inter- 2. Migration (in the electrical field be-
face electrode–electrolyte, electrochemical tween the anode and the cathode)
reactions are intrinsically more complex contributes to the movement of charged
than typical (thermal) chemical transfor- species. In most practical experiments,
mations (Figure 1). We mostly neglect the however, the concentration of support-
exact structure of the interface in the fol- ing electrolyte ions is much higher
lowing description. Transport of the educt (100–1000 : 1) than that of other ions.
Adsorption Diffusion layer Bulk

E E E’
Transport
Electrode
E Electron Chemical
transfer reactions
Fig. 1Steps constituting a
P typical organic electrode
Transport reaction; E, E : educt, P, P :
P P P’
product; circles indicate
d adsorbed molecules.

Hence, migration of the latter is sup- cox nF 0
= exp (E − E ) (1)
pressed. On the other hand, migration cred RT
becomes important at modified elec-
trodes or in electrolytes of low ion (n = number of electrons transferred,
concentration [9]. F = Faraday constant, R = gas con-
3. Convection (of the electrolyte liquid stant, T = temperature). The current is
phase as a whole) can be natural (due proportional to the amount of material
to thermal effects or density gradients) transported to the electrode in a time
or forced (principal mass transport unit.
mode in hydrodynamic techniques). 2. ET much slower than transport (ET
Still, however, close to the electrode control). The current follows the But-
surface a diffusion layer develops. ler–Volmer equation (2)

If we neglect migration, experiments can −αnF
i = i0 exp (E − E 0 )
be performed under conditions of minimal RT
convection, which are thus dominated
(1 − α)nF
by diffusion. Since δ increases with − exp (E − E 0 ) (2)
RT
time t in such a case, nonstationary
conditions exist. On the other hand, if where i0 defines the exchange current
convection dominates in the electrolyte at E = E 0 (irreversible ET). A physical
bulk, δ = f (t), and we approach stationary interpretation of α is related to the ET
conditions, as far as diffusion is concerned. transition state (see the comprehensive
discussion in ref. [10]). It is furthermore
1.2.1.3 Electron Transfer expected that α is potential dependent
The electron transfer (ET) at the interface and important mechanistic conclusions
between electrode and electrolyte is central follow [11, 12].
to an electrode reaction. Electrons pass 3. ET and transport have comparable
through the interface. Macroscopically we rates. This mixed-control situation is
observe a current i. characterized as quasi-reversible.
The transfer of an electron to (reduc-
tion) or from (oxidation) the substrate is an A given electrode reaction may corre-
activated process, characterized by a rate spond to any of these situations depending
constant ks , defined as the standard (or on the experimental conditions, in particu-
formal) potential E 0 , and the transfer coef- lar on the external control of mass transfer.
ficient α. The three situations mentioned
below can be distinguished: 1.2.1.4 Chemical Kinetic Steps
Most electrode reactions of interest to the
1. ET much faster than transport (trans- organic electrochemist involve chemical
port control). Electrochemical equilib- reaction steps. These are often assumed to
rium is attained at the electrode surface occur in a homogeneous solution, that is,
at all times and defined by the electrode not at the electrode surface itself. They are
potential E. The concentrations cox and described by the usual chemical kinetic
cred of oxidized and reduced forms of equations, for example, first- or second-
the redox couple, respectively, follow order reactions and may be reversible
the Nernst equation (1) (reversible ET) (chemical reversibility) or irreversible.
Chemical steps may precede or follow strong acids or bases are not necessary)
the transport and ET processes. In the and/or the additional selectivity introduced
former case, the electroactive species is in controlled-potential experiments.
formed in a preequilibrium. In the latter The reaction mechanisms of organic
case, we produce by ET some reactive electrode reactions are thus composed of at
species, which undergoes a (possibly least one ET step at the electrode as well as
complex) chemical transformation to a preceding and follow-up bond-breaking,
more stable product. bond-forming, or structural rearrange-
ment steps. These chemical steps may
1.2.1.5 Adsorption be concerted with the electron trans-
The involvement of specific attractive in- fer [15, 16]. The instrumental techniques
teractions of molecules with the electrode described in this chapter allow the in-
surface (adsorption) makes the electrode vestigation of the course of the reaction
process even more complex. The inten- accompanying the overall electrolysis.
sity of such interactions ranges from weak
(physisorption) to strong (chemical bonds 1.2.2.2 Nomenclature of Electrode
formed between adsorbate and electrode). Reaction Mechanisms
For some common organic electrochem- In order to classify the various mech-
ical reactions, for example, the Kolbe anisms of organic electrode reactions,
electrolysis of carboxylates [13], the adsorp- a specific nomenclature has been de-
tion of intermediates has been discussed. veloped [17]. It is often extended in an
informal way to accommodate particular
1.2.2 reaction features, and one may find addi-
Organic Electrode Reaction Mechanisms tional or deviant symbols.
Usually, however, electron transfers
1.2.2.1 Electron Transfer Initiates at the electrode are denoted by ‘‘E’’,
Chemistry while chemical steps not involving the
The majority of organic electrode reactions electrode are denoted by ‘‘C’’. The ET
is characterized by the generation of a may further be characterized as ‘‘Er ’’,
reactive intermediate at the electrode by ET ‘‘Eqr ’’, or ‘‘Ei ’’ in the reversible, quasi-
and subsequent reactions typical for that reversible, or irreversible case. It is usually
species. Thus, the oxidation or reduction not indicated how transport occurs. If the
step initiates the follow-up chemistry to C-step is a dimerization, the symbol ‘‘D’’ is
the reaction products (‘‘doing chemistry common, while an ET between two species
with electrodes’’ [14]). in a (homogeneous) solution is denoted
Species with electron deficiency (e.g. ‘‘SET’’ (for solution electron transfer) [18]
carbocations), unpaired electrons (e.g. or ‘‘DISP’’ (see, e.g. [19]).
radicals, radical ions), electron excess For more complex mechanisms, pic-
(e.g. carbanions), or those with unusual turesque names such as square, ladder,
oxidation states (e.g. metal complexes with fence [18] or cubic schemes [20] have been
low- or high-valent central atoms) are selected. In redox polymer films, addi-
produced at the electrode. Electrochemical tional transport of counterions, solvation,
generation of such intermediates may be and polymer reconfiguration are impor-
advantageous because of the mild reaction tant and four-dimensional hyper-cubes are
conditions employed (room temperature, needed to describe the reactions [21].
1.2.3 profile. In general, the electrode is located

Formal Description of Events at an at x = 0, and the electrolyte extends into
Electrode the positive x half-space. The bulk of
the solution is assumed at the right-hand
1.2.3.1 Current-Potential-Time side of the profile. Often, concentration
Relationships
values are normalized with respect to
The equations given in Section 1.2.1 in-
the bulk concentration of one species,
clude the most important quantities for and space coordinate values are normal-
understanding a reaction mechanism at ized with respect to the extension of
an electrode: current i, potential E, and the diffusion layer δ. Such concentra-
time t. Consequently, most techniques to tion profiles will be used in the following
investigate electroorganic reaction mecha- discussion.
nisms involve the determination of i or E
as a function of time (while the other one 1.2.4
of these quantities is kept constant) or as a Methods of Mechanistic Electroorganic
function of each other (while one is varied Chemistry
with t in a defined manner).
Similar i –E –t relationships are derived 1.2.4.1 Classification
theoretically from basic equations (simu- One of several possibilities to classify elec-
lation, see Section 1.4.1), on the basis of troanalytical methods is based on the quan-
a hypothesis for the reaction mechanism, tity that is controlled in the experiment,
and the experimental and the theoretical that is, current or potential. Alternatively,
results are compared. In this way, the hy- since diffusion is an important mode of
pothesis is either disproved, or proven to mass transport in most experiments, we
be consistent with the events at the elec- distinguish techniques with stationary or
trode. nonstationary diffusion. Finally, transient
methods are different from those that work
1.2.3.2 Concentration Profiles in an exhaustive way.
The current through the electrode is pro- Only a small selection of the variants in
portional to the flux of redox-active mate- the electrochemical literature can be men-
rial to the surface, which, in turn is related tioned here. Thus, impedance techniques
to the concentrations c of various species (small amplitude sinusoidal perturbation
near the interface. Thus, an equivalent de- at the electrode with observation of the
scription is based on the dependence of system’s response [22]) as well as polaro-
c on space x and t. Often a single space- graphic methods (at mercury electrodes)
coordinate suffices. More complex systems will not be described. Since the notion of
(e.g. ultramicroelectrodes) may require up a reaction mechanism requires consump-
to three space-coordinates. tion of substance, equilibrium techniques
Although it is difficult to determine the (such as potentiometry) will also not be
spatial distribution of species experimen- discussed here.
tally, it provides an illustrative view of
the electrode reaction. Simulations usu- 1.2.4.2 Controlled-Potential Techniques
ally provide values of c = f (x, t) for each Control of the potential E of that elec-
species as the primary result. The space trode where the electrode reaction occurs
dependence of c is termed a concentration (working electrode) is accomplished by a
Potentio/galvanostat
Computer,
Recorder
E
Function
generator
R
C W
Electrolyte
Fig. 2 Schematic representation of experimental set-up for

controlled-potential experiments; W: working, C: counter, R:
references electrodes.
potentiostat in a three-electrode arrange- transport (diffusion) limited region. After

ment (Figure 2). The current is passed some (pulse) time τ , E may be switched
through the working (W) and counter back to ER or another appropriate value
(C) electrodes, while E is measured with (double-step chronoamperometry).
respect to a currentless reference (R) elec- Starting at ER guarantees that at t <
trode. Often, a recording device and a 0, the concentration of the redox-active
function generator complement the exper- compound A, cA , equals cA0 at all x.
imental setup. The product concentration cB is usually
We will assume a simple reversible one- assumed to be zero. After E is stepped,
±e−
−− the concentrations of A and B at x = 0
electron redox process A −−−
− B in all
cases to introduce the techniques. adjust to conform to equation (1). These
An important property of the solution concentrations deviate from the bulk
to be investigated is the rest or open-circuit concentrations that remain at their initial
potential ER . This is the potential that the values throughout the experiment, and
working electrode develops in the solution a concentration gradient develops. As a
at equilibrium, that is, when no current result, A diffuses to the electrode, while B is
flows through the electrode. The value of produced at x = 0 and diffuses to the bulk.
ER depends on the components of the The resulting diffusion layer grows into
solution and the electrode itself. the solution with t (typically 10−2 cm after
Chronoamperometry is a technique in 10 s in common organic solvents). The
which a potential step is applied to the steepness of the concentration gradient
working electrode in a quiet solution at t = is high shortly after t = 0, and decreases
0 (Figure 3). Initially (t < 0), the electrode thereafter. This is reflected in the current
attains ER . For t > 0, a potential is response given by the Cottrell equation (3)
selected, which drives the desired electrode √
reaction. Often, but not necessarily (see, nFAcA0 D
i= √ (3)
e.g. References [23–25]) the latter is in the πt
0.6 30
0.5 20
Current, i • 106
Potential, E
0.4 10
0.3 0
[A]
[V]
0.2 −10
0.1 −20
0.0 −30
−0.1 −40
0.0 0.5 1.0 1.5 2.0 0.0 0.5 1.0 1.5 2.0
Time, t Time, t
(a) [s] (b) [s]
1.2 1.2
1.0 1.0
Concentration, c
Concentration, c
0.8 0.8
0.6 0.6
0.4 0.4
0.2 0.2
0.0 0.0
−0.2 −0.2
0.0 0.2 0.4 0.6 0.8 1.0 1.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2
(c) Distance, x (d) Distance, x
Fig. 3 Chronoamperometry: (a) typical profiles respectively at various times, increasing
excitation signal; (b) current response; and time shown by arrows] for a double-step
concentration profiles [(c) first step; (d) second chronoamperometric experiment (pulse time
step; educt: solid lines, product: dotted lines; five τ = 1s).
in the most simple case (with A = the charge Q, is recorded (Figure 4). This
electroactive
√ area of the electrode). Thus, quantity continuously increases during the
i t is a constant, and a plot of i vs. t −1/2 first part of the experiment (0 < t < τ ).
is a straight line. Integration of equation (3) yields
Switching back E to ER causes the √
concentrations at x = 0 to return to their 2nFAcA0 D √
Q= √ t (0 < t < τ ) (4)
original values with the concentration π
profiles changing accordingly. Now, B,
As soon as the potential is stepped back
which has accumulated in the diffusion
such that a current in the reverse direction
layer, diffuses toward the electrode and flows, the accumulated charge decreases
is transformed back to A. We observe a as shown:
current in the opposite direction. √
Any reaction that removes B from the so- 2nFAcA0 D √ √
Q= √ ( t − t − τ)
lution will influence the current response, π
allowing qualitative mechanistic conclu- (τ < t < 2τ ) (5)
sions. Furthermore, quantitative analysis
√
of chronoamperometric curves includes Thus, a√plot of
√ Q vs. t for the first, and
determination of n, A, or D, provided two Q vs. t − t − τ for the second part
of these quantities are known. of the curve results in two straight lines
Chronocoulometry is similar to chrono- (‘‘Anson plot’’ [26]). Adsorption of redox
amperometry, but the time integral of i, active species can simply be diagnosed
3.7 4
3.2 3
Charge, Q • 106
Charge, Q • 106
2.2 2
1.7 1
[C]
[C]
1.2 0
0.7 −1
0.2 −2
−0.3 −3
−0.2 0.3 0.8 1.3 1.8 2.3 0.0 0.2 0.4 0.6 0.8 1.0 1.2
Time, t Square root of time, t1/2
(a) [s] (b) [s1/2]
Fig. 4Chronocoulometry: (a) typical charge response; (b) Anson plot for a double-step
chronocoulometric experiment.
if the extrapolated Anson plot lines do not than chronoamperometry. Again, n, A, or

cross close to the origin [27]. An interesting D are accessible from chronocoulometric
characteristic of the chronocoulometric data.
curve is that Q(2τ )/Q(τ ) = 0.414, if no Linear sweep and cyclic voltammetry (LSV
follow-up reaction destroys B. If B reacts, and CV) are probably the most widely
however, this charge ratio increases. used techniques to investigate electrode
Because of its integral nature, chrono- reaction mechanisms. They are easy to
coulometry is less susceptible to noise apply experimentally, readily available in
0.7 400
0.6 300
Current, i • 106
0.5
Potential, E
200
0.4
100
[V]
[A]
0.3
0
0.2
0.1 −100
0.0 −200
−0.1 −300
0.00 0.02 0.04 0.06 0.08 0.10 0.12 0.14 −0.1 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7
Time, t Potential, E
(a) [s] (b) [V]
1.2 1.2
1.0 1.0
Concentration, c
Concentration, c
0.8 0.8
0.6 0.6
0.4 0.4
0.2 0.2
0.0 0.0
−0.2 −0.2
0.0 0.2 0.4 0.6 0.8 1.0 1.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2
(c) Distance, x (d) Distance, x
Fig. 5 Linear sweep and cyclic voltammetry: (a) dotted lines; five profiles respectively at various
typical excitation signal; (b) current response; times, increasing time shown by arrows] for a
and concentration profiles [(c) forward scan; cyclic voltammetric experiment.
(d) reverse scan; educt: solid lines, product:
commercial instruments, and provide a Besides determination of n, A, or D,

wealth of mechanistic information. In follow-up kinetics are accessible from
such experiments, the potential of the the influence on the position of the
working electrode is controlled by a peaks, and in particular, the intensity of
potential ramp (LSV) or one or more the reverse peak. Formation of products
potential triangle(s) (CV, Figure 5, see also that are electroactive within the potential
Volume 3, Chapter 2). window scanned causes the appearance of
The potential changes with a scan (or additional peaks. Furthermore, the shape
sweep) rate v = dE/dt. This quantity is of the peaks allows conclusions to be
easily variable and is one of the most drawn about the involvement of adsorption
important parameters for mechanistic processes.
analysis, defining the timescale of the
experiment. 1.2.4.3 Controlled-Current Techniques
In these techniques, the concentrations Current control of an electroanalytical
at the electrode do not immediately experiment is accomplished by a galvano-
attain their extreme values after the start or amperostat [29].
of the experiment. Rather, they change Chronopotentiometry is a transient cons-
with E or t according to equation (1). tant-current technique in which the po-
While the steepness of the concentration tential of the electrode is followed, as
profiles increases with E (forward scan), a function of time, in a quiet solution
simultaneously δ increases in the quiet (Figure 6). Double-step applications [30],
solution. The latter effect slows down the as well as programmed current experi-
increase of i with E, and finally (close to ments [31] have been described.
the limiting current region) leads to the Starting at ER , as soon as a current i
formation of a peak with a characteristic is imposed, the equivalent flux of redox-
asymmetric shape. On the reverse scan active substrate A to the electrode is
(after switching the scan direction at Eλ ), established. Since i is constant, the slope
products formed in the forward scan can of the concentration profile must also be
be detected (B, in the case discussed). constant. Thus, depletion of the substrate
The peak current in the forward scan is causes an increase in the diffusion layer
given by [28] thickness, while the steepness of the
profile does not change. The concentration
nF of A at x = 0 necessarily decreases.
ip = 0.4463nFAcA0 vD (6)
RT Simultaneously, cB (x = 0) increases. As
a consequence, E adjusts according to
or, for T = 298 K, equation (1).
√ After some transition time τ , cA (x = 0)
ip = (2.69 × 105 )n3/2 AcA0 vD (7) reaches a value of zero and no more
decrease is possible. Since δ still keeps
(Randles-Sevčik equation). The peak po- increasing, the concentration gradient
tential in the forward scan, Epf , is related becomes less steep. The current can no
to E 0 of the redox couple by Epf = E 0 + longer be maintained by the redox reaction
28 mV, and E 0 = (Epf + Epb )/2, where Epb of A. Now, E increases steeply until
is the potential of the peak on the reverse another electrode process is possible (not
scan. shown in Figure 6).
12 0.12
10
Current, i • 106
0.07
Potential, E
8
0.02
[A]
[V]
6
4 −0.03
2 −0.08
0
−0.13
0.0 0.2 0.4 0.6 0.8 1.0 0.0 0.2 0.4 0.6 0.8 1.0
Time, t Time, t
(a) [s] (b) [s]
1.2
Concentration, c
1.0
[mol l−1]
0.8
0.6
0.4
0.2
0.0
0.0 0.2 0.4 0.6 0.8 1.0 1.2
Distance, x
(c) [m]
Fig. 6 Chronopotentiometry: (a) typical excitation signal; (b) potential
response; (c) concentration profiles of educt for a chronopotentiometric
experiment (three profiles at various times, increasing time shown by arrow).
The relation between i and τ is given by Rotating disk voltammetry uses a po-
the Sand equation (8) tential scan to control the potential of
√ a specially designed working electrode,
1/2 nFAcA0 πD consisting of a disk embedded into the
iτ = (8)
2 lower cross section of a perpendicularly
mounted insulating shaft. The shaft is
Again, n, A, or D can be determined from
inserted into the electrolyte and rotated
chronopotentiometric experiments.
around its vertical axis with an angu-
lar velocity ω (RDE [32], Figure 7). The
1.2.4.4 Hydrodynamic Voltammetry electrolyte is set into a circular motion
In hydrodynamic techniques, convection and moves centrifugally along the elec-
is the principal mode of mass transport, trode surface. It is replenished by fresh
and is brought about by the controlled solution dragged up vertically from the
movement of the electrode in the solution bulk.
or by pumping the electrolyte through a Diffusion occurs across a distance of
pipe or channel. δ = 1.61D 1/3 ω−1/2 ν 1/6 (ν is the kine-
In a simple model, one assumes that matic viscosity of the electrolyte). At
convective mass transport keeps the con- ER , cA (x = 0) ≈ cA0 , diffusion is negligible
centration constant at some fixed distance and no current flows. Scanning E causes
δ from the solid wall. Thus, the diffusion cA (x = 0) to change, and a current results.
layer thickness is constant. Eventually, cA (x = 0) = 0 and a limiting
1.2
1.0
Current, i • 106
0.8
[A]
0.6
0.4
0.2
0.0
−0.6 −0.4 −0.2 0.0 0.2 0.4 0.6
Potential, E
(a) (b) (c) [V]
Fig. 7 Construction [section and bottom view, (a) RDE; (b) RRDE] of
rotating disk electrodes; and (c) typical RDE response.
current The fact that transport limits the rate

of the overall electrode reaction affects
ilim = 0.620nFAcA0 D 2/3 ω1/2 ν −1/6 (9) the fastest timescale accessible. Once
transport controls the rate, faster reaction
is reached [Levich equation (9)]. steps cannot be characterized. It is thus
Since products of the electrode process important to enhance mass transfer, for
are quickly transported out of the vicinity of example, by increased convection with
the electrode disk, use of the rotating disk high flow rates [37, 38].
electrode complements the more complex
rotating ring disk electrode (RRDE) [32]. 1.2.4.5 Exhaustive Electrolysis Techniques
Here, redox active products can be detected In contrast to the techniques discussed
at the ring electrode, which is held at a up to now in which only a small part
separately controlled potential. of the substrate present in the electrolyte
Channel techniques employ rectangu- is consumed, we will now consider
lar ducts through which the electrolyte approaches that exhaustively convert the
flows. The electrode is embedded into substrate to the product. Typically, the
the wall [33]. Under suitable geomet- electrodes used have a comparatively large
rical conditions [2] a parabolic veloc- area, and the electrolyte is stirred in order
ity profile develops. Potential-controlled to increase mass transport. Exhaustive
steady state (diffusion limiting condi- electrolyses can be performed potentio- or
tions) and transient experiments are pos- galvanostatically.
sible [34]. Similar to the Levich equation In potentiostatic exhaustive electrolysis,
at the RDE, the diffusion limiting cur- the potential of the working electrode
rent is is constant throughout the experiment.
The substrate is transported by convection
1/3 −1/3 2/3 and diffusion to the working electrode
ilim = 1.165nF cA0 D 2/3 U h
wxE
surface. The current decreases with the
(10)
bulk concentration of the substrate, if
(with U = mean solution velocity, xE =
no further electron transfers occur. The
electrode length, h = half-height of chan-
charge transferred is
nel, w = width of the electrode). Experi-
tend
mental variables include U and xE (arrays
Q= i dt (11)
of microbands) [35, 36]. 0
with tend denoting the time when the 1.3

experiment is stopped. A frequent, but not How to Gain Access to Kinetics,
unique stopping criterion is the remaining Thermodynamics, and Mechanisms of
current, for example, 1% of the initial i. Electroorganic Reactions
One could also test for disappearance of 1.3.1
the substrate or some intermediate, in situ Qualitative and Quantitative Investigation
or in samples taken from the electrolyte. of Electrode Reaction Mechanisms
Typically, the duration of a potentiostatic
electrolysis is much larger than that of a Two extreme forms of mechanistic inves-
transient experiment as discussed above. tigations in organic electrochemistry are
Q can be related to the amount m frequently applied:
of substrate with molecular mass M 1. Qualitative analysis has the main objec-
consumed. From Faraday’s first law (Q = tive of confirming a given mechanistic
nF m/M), n is available. hypothesis by rejection of conflicting al-
From an exhaustive potentiostatic elec- ternatives. This may be applied to single
trolysis, the product(s) formed at the elementary steps, the intermediates, or
selected electrode potential can be isolated. how the steps are linked together.
Preparative and analytical techniques are 2. Quantitative analysis relies on a highly
available to determine the composition probable mechanistic hypothesis and
of the product mixture and the structure determines as many as possible kinetic,
of its components. Mechanistic reason- thermodynamic, and/or transport pa-
ing will often allow defining the reaction rameters for the various steps. This
steps. Even more information about the is often a complex problem, since the
reaction can be gained from electrolysis values of the parameters are usually cor-
experiments at various defined potentials, related, their relation to experimental
for example, after each peak in the cyclic data is nonlinear, and the data contain
voltammogram of the substrate. artifacts and statistical errors [40, 41].
In contrast, in galvanostatic exhaustive Both types of mechanistic analysis are
electrolysis the current through the working supported by the instrumental techniques
electrode is kept constant. As in chronopo- discussed here.
tentiometry, this will result in a constant
flux of electroactive material to the surface. 1.3.2
Consequently, the electrode potential will General Recommendations for Mechanistic
vary during the experiment. As a result, at Analysis
different times various electrode processes
may be induced. Hence, the results of gal- In general, for a mechanistic analysis, as
vanostatic and potentiostatic electrolyses many facets as possible of the investigated
will not necessarily be identical. electrode reaction should be taken into
account and the various experimental
The determination of charge in galvano-
parameters be varied as widely as possible.
static electrolysis is particularly simple,
Among these are
since i = f (t): Q = it. Again, a suit-
able protocol for endpoint detection must • Time scale: This is particularly important
be defined [39], and product isolation is for kinetic studies and the determina-
possible. tion of rate constants.
1.3 How to Gain Access to Kinetics, Thermodynamics, and Mechanisms of Electroorganic Reactions 15
• Concentration: The dependence of re- or are caused by non-Faradaic pro-

sults on concentration indicates chem- cesses (charging of the double layer).
ical reactions of an order higher than They are at least approximately cor-
unity. rected by subtraction of a blank curve
• Presence of reagents: Formation of recorded in the electrolyte without sub-
intermediates may be proven by strate.
their reaction with intentionally added • iR drop is caused by the resistance R
reagents, for example, nucleophiles between the reference and the work-
to quench electrogenerated carbenium ing electrode in a three-electrode cell.
ions. Characteristic changes are It is particularly awkward in low-
expected, for example, peaks in CV may conductivity electrolytes and distorts
disappear. curves in a nonlinear way. Compen-
sation in commercial instruments is
Usually, the experimental results are
often possible, and procedures for cor-
compared with the theoretical model
rection have also been given [47, 48].
simulations. Again, it is important to However, it is best to avoid an iR drop
consider wide ranges of experimental by decreasing i [decreasing c or A (ul-
conditions that have to be adequately tramicroelectrodes, Section 1.4.2)] or R
modeled using a single set of parameters. (increasing conductivity or decreasing
Comparison is done by distance between reference and working
electrodes).
• data transformation. Suitable transfor-
mations of the experimental data lead
to straight lines (e.g. Anson plot in 1.3.3
chronocoulometry) or similar simple Some Mechanistic Examples
curves (semi-integration or differentia-
tion [42]). 1.3.3.1 Pure ET Reactions
• feature analysis. The experimental curves If no chemical steps are coupled to the ET
exhibit features (e.g. peaks in CV) at the electrode, the reaction mechanism is
that change characteristically with the fully described by E 0 (thermodynamics),
experimental conditions. The results are n (stoichiometry), D (transport), as well as
usually compared to working curves [28] ks , and α (kinetics). It is characteristic to
or surfaces [43, 44]. find a fully developed reverse peak in the
• full curve analysis. Global analysis of cyclic voltammogram [49]. Qualitatively, it
experimental and theoretical data is is important to diagnose full diffusion
applied by comparing entire curves. This control (Er ). Cyclic voltammetry allows
is used to great advantage in simulation this by inspection of the peak potential
procedures [45, 46]. difference
Ep = Epf − Epb . For Er ,
Ep
is independent of v, while for Eqr an
Of course, experimental artifacts should increase of v (faster timescale) causes
Ep
be avoided. In particular, in mechanistic to increase (Figure 8a) [50].
electroorganic work these are While E 0 follows from CV directly (Sec-
tion 1.2.4), determination of the other pa-
• Background currents are current compo- rameters is more complex. For diffusion-
nents not related to the ET of substrates controlled ETs, n follows from
Ep =
or products, but rather to impurities 58/n mV, and D is calculated from
40
80
Current, i • 106
30
Current, i • 106
60
20 40
[A]
10 20
[A]
0 0
−20
−10 −40
−20 −60
−30 −80
−0.1 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 −0.1 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
Potential, E Potential, E
(a) [V] (b) [V]
Fig. 8 Typical cyclic voltammograms of pure formal potentials in an Er Er reaction (difference
electron transfer reactions; (a) effect of of formal potentials,
E0 , decreases from
quasi-reversibility (ks decreases from solid to dash-dotted through dashed to solid line; in the
dashed line); (b) effect of relative values of latter case, potential inversion occurs).
equation (7). Alternatively, a combination is assumed to be 0.5 in organic electrode

of equations (7) and either (3) or (4) yields reactions, but clearly this is only a rough
n [51]. Exhaustive electrolyses also give n approximation.
and allow product generation. Because of Transfer of several electrons yields n > 1
the longer timescale as compared to tran- from the above procedures, but CV addi-
sient methods, the results may differ from tionally shows the relative thermodynam-
the CV or potential step techniques. Of- ics and depending on the individual E 0
ten, starting with stable organic molecules, values, various shapes of i/E curves are
radical ions are produced, which can be in- obtained (Figure 8b). If the two E 0 are suf-
vestigated by ESR spectroelectrochemistry ficiently different (
E 0 > 100 mV), two
(Section 1.4.4). Note, that n must be an separated peak couples occur (dash-dotted
integer value. line). On the other hand, if
E 0 decreases
Kinetic information for Eqr reactions is below ≈100 mV, the voltammetric signals
not available from techniques that work in merge (dashed line).
the diffusion-controlled regime. However, Further, interesting cases are encoun-
again, CV allows determination of ks from tered in ‘‘inverted potential’’ [54] situations
the dependence of
Ep on v [50, 52, 53]. (solid line in Figure 8b, second ET thermo-
The transfer coefficient is also accessible dynamically easier than the first one), and
from cyclic voltammograms [53]. Often α for dendrimers with a large number of
40
30
Current, i • 106
20
10
[A]
0 Fig. 9 Typical cyclic

−10 voltammograms of an EC
−20 reaction system; rate of
−30 follow-up reaction increases
−0.1 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7
from short-dashed through
Potential, E dotted, dash-dotted and
[V] long-dashed to solid curve.
1.3 How to Gain Access to Kinetics, Thermodynamics, and Mechanisms of Electroorganic Reactions 17
redox-active units, which undergo ET at (for an oxidation; extension to reduction is

approximately the same potential [55]. obvious). In such cases, homogeneous ETs
[disproportionation, Reaction (13)] have
1.3.3.2 Follow-up Reactions also to be considered:
Irreversible follow-up reactions (most −−
B + C−−−
−A + D (13)
simple case: EC mechanism) decrease
the concentration of the primary redox where the equilibrium constant is related
product. This is again diagnosed in CV to the E 0 of the two heterogeneous ETs.
(Figure 9) and also in chronocoulome- Several variants are discussed in the
try. Timescale variation in CV allows literature [18, 56, 57]. Figure 10 shows
to modulate the importance of the C- some cyclic voltammograms. The height
step: at fast v the chemical reaction will of the second peak depends on the rate
have no influence on the curves, while of the C-step. In chronoamperometry, the
at slower v all product has reacted and formation of a redox-active product leads
the reverse peak disappears. A govern- to an increase in the apparent n during the
ing factor is k/a (k = rate constant of experiment (e.g. from n = 1 to n = 2). A
C-step, a = nF v/RT ). Thus, for a qual- plot of i vs. t −1/2 switches from a straight
itative interpretation, the peak current line for n = 1 at small t to the one for n = 2
ratio in CV is evaluated as a func- at large t.
tion of v (and Eλ ) in order to calcu- If, for an oxidation step, the chemical
late k [49]. Also, Ep and ip depend on reaction of B leads to the oxidized form of
k/a [28]. the second redox couple B (and not the
Reversible follow-up reactions may just reduced one as in the earlier case) and a
shift the entire voltammetric signals (fast second chemical transformation from A
equilibration) on the E axis, or lead to ef- leads back to A [reaction (14)], we arrive
fects approaching those of the irreversible at a square scheme (Figure 11), which
case [28]. forms the basis for many important redox
The most important are cases in which systems [18, 58]. Again SET steps
the product of the C-step is again electroac- A + B
−−
−−−
−A + B (14)
tive [ECE mechanism, Reaction (12)]:
can be involved, resulting in rather un-
−e− k −e− usual voltammograms under certain con-
−−
A−−−
−−
− B −−−→ C −−−
−D (12) ditions [18, 59].
40
30
Current, i • 106
20
10
[A]
0
Fig. 10 Typical cyclic −10
voltammograms of ECE −20
reaction systems; rate of C-step −30
−0.10.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
increases from dash-dotted
through dashed and dotted to Potential, E
solid curve. [V]
Fig. 11 The square scheme

± e−
reaction mechanism.
A B
A′ B′
± e−
1.3.3.3 Preequilibria to ETs Kinetics and thermodynamics will influ-

The square scheme discussed above al- ence the exact appearance of the concen-
ready includes a further common motif tration profiles. Figure 12 shows some CE
in electroorganic mechanisms: reaction voltammograms. In particular, chronopo-
A−−−−
−−A forms a preequilibrium to both
tentiometry was used for analyses[60, 61],
ETs in the scheme. The response of such since for high i
a system in CV depends particularly on √
π √ K
the equilibrium constant K = [A]/[A ] and iτ 1/2 = nFAc0 D (15)
the rate constants kA→A and kA →A . If the 2 1+K
k are large (reaction at equilibrium), only (with total concentration c0 = cA0 +
that ET will occur, which is thermody- cA0 ) [62]. Furthermore, hydrodynamic
namically easier (smaller E 0 ). All material techniques were also employed [63, 64].
consumed by that ET will immediately be
replenished through the equilibrium re-
action. On the other hand, if the k are 1.3.3.4Catalytic Reactions
small, two peaks will be observed with In some reactions the product of an
their relative heights proportional to the ET at the electrode reacts back to the
±e− k
equilibrium concentrations of A and A , starting compound: A − −
−−−
− B −−−→ A.
thus allowing determination of K. This mechanistic motif is found in me-
Both partners of the preequilibrium are diated electrode reactions [65] or in sen-
not always electroactive (CE mechanism). sor applications [66]. The reformation of
1.6
Current, i • 106
1.1
0.6
[A]
0.1
−0.4
−0.9 Fig. 12 Typical cyclic
−1.4 voltammograms of
−1.9 preequilibrium systems; kinetics
−0.1 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7
of preequilibrium become
Potential, E slower from dotted through
[V] dashed to solid curve.
1.4 How to Gain Additional Information about Electroorganic Reaction Mechanisms 19
500 80
70
400
Current, i • 106
Current, i • 106
60
300 50
40
[A]
[A]
200
30
100 20
0 10
0
−100 −10
0.0 0.2 0.4 0.6 0.8 1.0 1.2 −0.1 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7
Time, t Potential, E
(a) [s] (b) [V]
Fig. 13 Typical (a) chronoampero- and (b) cyclic voltammogram of a catalytic system.
the electroactive A leads to an increase mechanisms, simulation is an indispens-

in current and a decrease of diffu- able tool for both types of analyses de-
sional effects. Thus, in chronoamperom- scribed in Section 1.3.1. For a simulation,
etry, i reaches a nonzero limiting value one needs a mechanistic hypothesis that in
(Figure 13a), while in CV the peak disap- some programs is translated into the gov-
pears in favor of an S-shaped i/E curve erning equations automatically [45, 68, 69].
(Figure 13b). From the limiting CV cur- There are various parameters defining the
rent, the rate constant k is accessible reaction steps in detail, for example, rate
from [28, 67] constants or formal potentials. One solves
√ the equations for given values of these
i = nFAc0 Dk (16) parameters and compares the results to ex-
perimental curves in an iterative process,
until a ‘‘best fit’’ is obtained. Automatic
1.4
fitting is also available [45]. Alternatively,
How to Gain Additional Information about
it is illustrating to see how variations in
Electroorganic Reaction Mechanisms
mechanism and/or parameters change the
1.4.1 resulting curves.
Simulation It is of particular importance to follow
the guidelines provided in Section 1.3.2
A simulation (Volume 3, Chapter 3.1) is in comparing experiments and simula-
the reproduction of an electroanalytical tions.
experiment in the form of a set of math-
ematical equations and their solutions, 1.4.2
usually on a digital computer [7]. The equa- Ultramicroelectrodes
tions express a physical model of the real
experiment. Thus, the main steps of the In previous sections we have implicitly as-
electrode process (see Section 1.2.1) are sumed that diffusion occurs perpendicular
included. to the electrode surface (semi-infinite lin-
Various numerical techniques are em- ear diffusion). If we decrease the size of
ployed, and commercial programs are the electrode to values roughly in the order
available, mostly for the CV technique [7]. of the size of diffusion layers, this assump-
For the elucidation of electrode reaction tion becomes invalid. Now, additional
Function
generator
Potentio/galvanostat Computer,
Recorder
Oscillator Frequency
counter
R Quartz crystal with

electrodes
C W
Electrolyte
Fig. 14 Set-up of an electrogravimetric experiment with an

electrochemical quartz crystal microbalance.
diffusion components parallel to the sur- 1.4.3

face become important. Thus, the current Electrogravimetry
densities are increased. It is common to
call disk electrodes with radii ≤20 µm ‘‘ul- If the electrode process results in the
tramicroelectrodes’’ (UMEs) [8]. deposition of some product at the electrode
UMEs decrease the effects of non- surface, or in changes of composition of a
Faradaic currents and of the iR drop. precipitate or film on the electrode, mass
At usual timescales, diffusional transport changes are coupled to the ET. Usually,
these changes are small (ng– µg) and
becomes stationary after short settling
special techniques are necessary for their
times, and the enhanced mass transport
exact determination.
leads to a decrease of reaction effects.
A technique for such measurements
On the other hand, in voltammetry very
is the electrochemical quartz crystal
high scan rates (v up to 106 Vs−1 )
microbalance (EQCM; Figure 14) [71].
become accessible, which is important Here, the working electrode is part of a
for the study of very fast chemical steps. quartz crystal oscillator that is mounted
For organic reactions, minimization of on the wall of the electrochemical cell
the iR drop is of practical value and and exposed to the electrolyte. The
highly nonpolar solvents (e.g. benzene resonance frequency f of the quartz crystal
or hexane [8]) have been used with low is proportional to mass changes
m:
or vanishing concentrations of supporting
f ∼
m. With base frequencies around
electrolyte. In scanning electrochemical 10 MHz, the determination of
m in the
microscopy (SECM [70]), the small size ng range is possible.
of UMEs is exploited to localize electrode Electrogravimetric experiments lead to
processes in the µm scale. a mechanistic understanding of polymer
1.5 Conclusion 21
film formation on electrodes, support use in electroorganic chemistry. These

the study of film morphology and the techniques greatly help determine and
diffusional as well as the migrational understand the mechanistic course of
transport into and within such films [72]. electrode reactions in a qualitative and
quantitative way. Besides briefly describ-
1.4.4 ing the methods themselves, the chapter
Spectroelectrochemistry provides examples for their application
for some frequently encountered reaction
Although the instrumental techniques de- mechanisms. In particular, cyclic voltam-
scribed here give detailed mechanistic metry is probably the most often used
information, they do not provide an in- of these techniques, but other methods
sight into the structure of intermediates. should also be applied if necessary, and
If we, however, combine electrochemical extensions, as discussed in Section 1.4, are
and spectroscopic methods, this is ad- expected to gain additional importance in
vantageously accomplished (spectroelec- the future.
trochemistry) [73]. Various spectroscopies
have been coupled with electrochemical Acknowledgment
experiments, among them ESR [74], opti-
cal [75], and NMR spectroscopy [76, 77], as The authors thank Kai Ludwig for technical
well as mass spectrometry [78, 79]. assistance in preparing Figures 6 and 7.
Three types of spectroelectrochemical
experiments are useful for mechanistic References
studies:
1. J.-M. Savéant, Pure Appl. Chem. 1997, 69,
• Spectral resolution records spectra at 269–271.
different potentials, for example, during 2. P. R. Unwin, J. Chem. Soc., Faraday Trans.
a CV scan. This allows structural 1998, 94, 3183–3195.
characterization of intermediates. 3. W. Podroužek, Recl. Trav. Chim. 1925, 44,
591–599.
• Temporal resolution records the inten- 4. G. L. Booman, W. B. Holbrook, Anal. Chem.
sity of a spectroscopic signal with t, 1963, 35, 1793–1809.
giving access to formation and decay 5. C. K. Mann, Nonaqueous solvents for elec-
kinetics. trochemical use in Electroanalytical Chemistry
(Ed.: A. J. Bard), Marcel Dekker, New York,
• Spatial resolution [80] leads to informa-
1969, pp. 57–134, Vol. 3.
tion on the distribution of species within 6. R. R. Schroeder, Comput. Chem. Instrum.
the diffusion layer. Distinction between 1972, 2, 263–350.
alternative mechanisms has been re- 7. B. Speiser, Numerical simulation of elec-
ported [81]. troanalytical experiments: recent advances
in methodology in Electroanalytical Chem-
istry (Eds.: A. J. Bard, I. Rubinstein), Marcel
Dekker, New York, 1996, pp. 1–108, Vol. 19.
1.5 8. J. Heinze, Angew. Chem. 1993, 105,
Conclusion 1327–1349; Angew. Chem. Int. Ed. Engl. 1993,
32, 1268–1288.
9. M. Ciszkowska, Z. Stojek, J. Electroanal.
This chapter discussed some of the Chem. 1999, 466, 129–143.
more important electroanalytical tech- 10. J. O’M. Bockris, Z. Nagy, J. Chem. Educ.
niques with particular emphasis on their 1973, 50, 839–843.
11. J.-M. Savéant, D. Tessier, Faraday Discuss. 36. F. Prieto, J. A. Alden, M. Feldman et al.,
Chem. Soc. 1982, 74, 57–72. Electroanalysis 1999, 11, 541–545.
12. S. Antonello, F. Maran, J. Am. Chem. Soc. 37. N. V. Rees, R. A. Dryfe, J. A. Cooper et al., J.
1999, 121, 9668–9676. Phys. Chem. 1995, 99, 7096–7101.
13. E. Klocke, A. Matzeit, M. Gockeln et al., 38. N. V. Rees, J. A. Alden, R. A. Dryfe et al., J.
Chem. Ber. 1993, 126, 1623–1630. Phys. Chem. 1995, 99, 14 813–14 818.
14. D. H. Evans, Acc. Chem. Res. 1977, 10, 39. V. D. Parker, Acta Chem. Scand. 1970, 24,
313–319. 2768–2774.
15. J.-M. Savéant, Adv. Electron Transfer Chem. 40. B. Speiser, Anal. Chem. 1985, 57, 1390–1397.
1994, 4, 53–116. 41. L. K. Bieniasz, B. Speiser, J. Electroanal.
16. B. Speiser, Angew. Chem. 1996, 108, Chem. 1998, 458, 209–229.
2623–2626; Angew. Chem. Int. Ed. Engl. 1996, 42. J.-S. Yu, Z.-X. Zhang, J. Electroanal. Chem.
35, 2471–2474. 1996, 403, 1–9.
17. E. Vieil, G. Cauquis, J. Electroanal. Chem. 43. B. Speiser, J. Electroanal. Chem. 1991, 301,
1983, 148, 183–200. 15–35.
18. D. H. Evans, Chem. Rev. 1990, 90, 739–751. 44. J. A. Alden, R. G. Compton, J. Phys. Chem. B
19. R. G. Compton, R. G. Wellington, P. J. 1997, 101, 9741–9750.
Dobson et al., J. Electroanal. Chem. 1994, 370, 45. M. Rudolph, D. P. Reddy, S. W. Feldberg,
129–133. Anal. Chem. 1994, 66, 589A–600A.
20. E. Laviron, R. Meunier-Prest, J. Electroanal. 46. C. G. Zoski, K. B. Oldham, P. J. Mahon et al.,
Chem. 1992, 324, 1–18. J. Electroanal. Chem. 1991, 297, 1–17.
21. A. R. Hillman, S. Bruckenstein, J. Chem. 47. D. Britz, J. Electroanal. Chem. 1978, 88,
Soc., Faraday Trans. 1993, 89, 3779–3782.
309–352.
22. A. J. Bard, L. R. Faulkner, Electrochemical
48. E. Eichhorn, A. Rieker, B. Speiser, Anal.
Methods. Fundamentals and Applications, 2nd
Chim. Acta 1992, 256, 243–249.
ed., Wiley, New York, 2001, pp. 368–416.
49. R. S. Nicholson, Anal. Chem. 1966, 38, 1406.
23. L. Marcoux, J. Phys. Chem. 1972, 76,
50. R. S. Nicholson, Anal. Chem. 1965, 37,
3254–3259.
667–671.
24. L. Marcoux, T. J. P. O’Brien, J. Phys. Chem.
51. P. A. Malachesky, Anal. Chem. 1969, 41,
1972, 76, 1666–1668.
1493–1494.
25. F. Magno, G. Bontempelli, Anal. Chem. 1981,
53, 599–603. 52. E. Ahlberg, V. D. Parker, Acta Chem. Scand.
26. J. Kim, L. R. Faulkner, Anal. Chem. 1984, 56, 1980, B34, 71, 72.
874–880. 53. B. Scharbert, B. Speiser, J. Chemomet. 1988,
27. F. C. Anson, Anal. Chem. 1966, 38, 54–57. 3, 61–80.
28. R. S. Nicholson, I. Shain, Anal. Chem. 1964 54. D. H. Evans, K. Hu, J. Chem. Soc., Faraday
36, 706–723. Trans. 1996, 92, 3983–3990.
29. P. T. Kissinger, Introduction to analog in- 55. S. Nlate, J. Ruiz, V. Sartor et al., Chem. Eur.
strumentation in Laboratory Techniques in J. 2000 6, 2544–2553.
Electroanalytical Chemistry (Eds.: P. T. Kissin- 56. C. Amatore, J. M. Savéant, J. Electroanal.
ger, W. R. Heineman), 2nd ed., Marcel Chem. 1977, 85, 27–46.
Dekker, New York, 1996 pp. 165–194. 57. S. W. Feldberg, L. Jeftic, J. Phys. Chem. 1972,
30. O. Dračka, O. Fischer, Collect. Czech. Chem. 76, 2439–2446.
Commun. 1979, 44, 1869–1876. 58. E. Eichhorn, A. Rieker, B. Speiser et al., In-
31. L. M. Abrantes, J. González, A. Molina et al., org. Chem. 1997, 36, 3307–3317.
Electrochim. Acta 1999, 45, 457–468. 59. M. Dietrich, J. Heinze, H. Fischer et al.,
32. F. Opekar, P. Beran, J. Electroanal. Chem. Angew. Chem. 1986, 98, 999, 1000.
1976, 69, 1–105. 60. H. B. Herman, A. J. Bard, J. Phys. Chem.
33. J. A. Cooper, R. G. Compton, Electroanalysis 1966, 70, 396–404.
1998, 10, 141–155. 61. J. Galvez, A. Molina, J. Electroanal. Chem.
34. R. G. Compton, P. R. Unwin, J. Electroanal. 1983, 146, 221–232.
Chem. 1986, 206, 57–67. 62. D. D. Macdonald, Transient Techniques in
35. F. Prieto, B. A. Coles, R. G. Compton, J. Electrochemistry, Plenum Press, New York,
Phys. Chem. B 1998, 102, 7442–7447. 1977.
1.5 Conclusion 23
63. R. D. Martin, P. R. Unwin, J. Electroanal. 72. D. A. Buttry, M. D. Ward, Chem. Rev. 1992,
Chem. 1995, 397, 325–329. 92, 1355–1379.
64. S. L. Lanny Ng, H. Y. Cheh, J. Electrochem. 73. W. Plieth, G. S. Wilson, C. Gutiérrez de la
Soc. 1986, 133, 1385–1388. Fe, Pure Appl. Chem. 1998, 70, 1395–1414.
65. E. Steckhan, Angew. Chem. 1986, 98, 74. I. B. Goldberg, T. M. McKinney, Principles
681–699; Angew. Chem. Int. Ed. Engl. 1986, and techniques of electrochemical-electron
25, 693. paramagnetic resonance experiments in Lab-
66. K. Yokoyama, Y. Kayanuma, Anal. Chem. oratory Techniques in Electroanalytical Chem-
1998, 70, 3368–3376. istry (Eds.: P. T. Kissinger, W. R. Heineman),
67. J. M. Savéant, E. Vianello, Adv. Polarogr. 2nd ed., Marcel Dekker, New York, 1996,
1960, 2, 367–374. pp. 901–960.
68. L. K. Bieniasz, J. Electroanal. Chem. 1996, 75. W. R. Heineman, Anal. Chem. 1978, 50,
406, 33–43. 390A–402A.
69. L. K. Bieniasz, J. Electroanal. Chem. 1996, 76. D. W. Mincey, M. J. Popovich, P. J. Faustino
406, 45–52. et al., Anal. Chem. 1990, 62, 1197–1200.
70. A. J. Bard, F.-R. F. Fan, M. Mirkin, Scan- 77. P. D. Prenzler, R. Bramley, S. R. Down-
ning electrochemical microscopy in Physical ing et al., Electrochem. Commun. 2000, 2,
Electrochemistry. Principles, Methods, and Ap- 516–521.
plications (Ed.: I. Rubinstein), Monographs 78. M. C. S. Regino, A. Brajter-Toth, Anal. Chem.
in Electroanalytical Chemistry and Electro- 1997, 69, 5067–5072.
chemistry, Marcel Dekker, New York, 1995, 79. G. Hambitzer, J. Heitbaum, I. Stassen, J.
pp. 209–242. Electroanal. Chem. 1998, 447, 117–124.
71. M. D. Ward, Principles and applications 80. C.-C. Jan, R. L. McCreery, Anal. Chem. 1986,
of the electrochemical quartz crystal mi- 58, 2771–2777.
crobalance in Physical Electrochemistry (Ed.: 81. A. Deputy, H.-P. Wu, R. L. McCreery, J.
I. Rubinstein), Marcel Dekker, New York, Phys. Chem. 1990, 94, 3620–3624.
1995, pp. 293–338.
25
2
Practical Aspects of Preparative
Scale Electrolysis
..
Jakob J orissen
..
Universit at Dortmund, Dortmund, Germany
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
2.2 Target and Scale of the Investigations . . . . . . . . . . . . . . . . . . . . . 30
2.3 Principles of Electrochemical Cell Operation . . . . . . . . . . . . . . . . 31

2.3.1 Essential Definitions for Electroorganic Reactions . . . . . . . . . . . . . 31
2.3.2 Controlling of the Electrochemical Reaction Rate by Electrode Potential
and Cell Current . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
2.3.2.1 General Correlations between Electrode Potential and Current Density 31
2.3.2.1.1 Equilibrium Potential . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
2.3.2.1.2 Overvoltage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Charge transfer overvoltage . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Concentration overvoltage (reaction overvoltage and diffusion
overvoltage) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
2.3.2.1.3 Limiting Current Density . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
2.3.2.1.4 Side-reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
2.3.2.1.5 Possible Problems in Electroorganic Reaction Systems . . . . . . . . . . 34
2.3.2.1.6 Overvoltage Due to Electrolyte and Cell Separator Resistance . . . . . 34
2.3.2.1.7 Cell Voltage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
2.3.2.2 Operation with Constant Cell Current (Galvanostatic Operation) . . . 35
2.3.2.3 Operation with Constant Electrode Potential (Potentiostatic Operation) 36
2.3.3 Undivided or Divided Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
2.3.4 Batch Operation or Flow-through Cells . . . . . . . . . . . . . . . . . . . . 38
2.4 Components of Electroorganic Reaction Systems . . . . . . . . . . . . . 38

2.4.1 Electrodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
2.4.1.1 Examples of Electrode Materials . . . . . . . . . . . . . . . . . . . . . . . . . 40
2.4.1.1.1 Anode Materials: General Requirements . . . . . . . . . . . . . . . . . . . 40
2.4.1.1.2 Cathode Materials: General Requirements . . . . . . . . . . . . . . . . . . 40
26 2 Practical Aspects of Preparative Scale Electrolysis
2.4.1.1.3 Platinum, Platinum Metals or their Alloys, and Other Noble Metals . 41
Anode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Cathode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
2.4.1.1.4 Nickel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Anode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Cathode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
2.4.1.1.5 Iron, Stainless Steel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
Cathode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
2.4.1.1.6 Lead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
Anode (lead dioxide) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
Cathode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
2.4.1.1.7 Mercury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
Cathode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
2.4.1.1.8 Carbon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
Anode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Cathode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
2.4.1.1.9 Ceramic Materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
2.4.1.1.10 Coated Electrodes and Carrier Materials . . . . . . . . . . . . . . . . . . . 44
Titanium as a carrier metal . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Metal oxide coatings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Dimension stable anodes (DSA ) . . . . . . . . . . . . . . . . . . . . . . . . 45
Diamond coating (boron doped) . . . . . . . . . . . . . . . . . . . . . . . . . 45
2.4.1.2 Examples of Electrode Types and their Special Properties . . . . . . . . 45
2.4.1.2.1 Smooth or Porous Electrodes . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
2.4.1.2.2 Gas Evolving Electrodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
2.4.1.2.3 Gas Diffusion Electrodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
2.4.1.2.4 Sacrificial Anodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
2.4.2 Electrolytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
2.4.2.1 Solvents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
2.4.2.2 Supporting Electrolytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
2.4.2.3 Examples of Electrolytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
2.4.2.3.1 Aqueous Electrolytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
2.4.2.3.2 Electrochemistry Using Emul-sions . . . . . . . . . . . . . . . . . . . . . . 50
2.4.2.3.3 Electrolytes Based on Nonaqueous Protic Solvents . . . . . . . . . . . . . 50
2.4.2.3.4 Electrolytes Based on Aprotic Solvents . . . . . . . . . . . . . . . . . . . . . 50
2.4.2.3.5 Molten Salts as Electrolytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
2.4.2.3.6 Liquefied or Supercritical Gases as Solvents for Electrolytes . . . . . . 51
2.4.2.3.7 Solid Polymer Electrolyte Techno-logy . . . . . . . . . . . . . . . . . . . . . 51
2.4.3 Cell Separators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
2.4.3.1 Porous Materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
2.4.3.2 Ion-exchange Membranes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
2 Practical Aspects of Preparative Scale Electrolysis 27
2.5 Electrochemical Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

2.5.1 Requirements in Electrochemical Cells . . . . . . . . . . . . . . . . . . . . 54
2.5.1.1 Uniform Current Density . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
2.5.1.2 Uniform Mixing and Mass Transfer . . . . . . . . . . . . . . . . . . . . . . 55
2.5.1.3 Temperature Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
2.5.1.4 Construction Materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
2.5.1.5 Mass and Charge Balancing . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
2.5.1.6 Electrode Potential Measurement . . . . . . . . . . . . . . . . . . . . . . . . 61
2.5.1.6.1 Reference Electrodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
2.5.1.6.2 Diffusion Potentials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
2.5.1.6.3 Luggin Capillaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
2.5.2 Examples of Electrochemical Cells . . . . . . . . . . . . . . . . . . . . . . . 64
2.5.2.1 ‘‘H-cell’’ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
2.5.2.2 Beaker Glass Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
2.5.2.3 Flow-through Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
2.5.2.4 Industrial Scale Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
2.5.2.4.1 Parallel-plate and Frame Cells (Filter Press Cells) . . . . . . . . . . . . . 67
2.5.2.4.2 Capillary Gap Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
2.5.2.4.3 Swiss Roll Cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
2.5.2.4.4 Innovative Cell Constructions . . . . . . . . . . . . . . . . . . . . . . . . . . 70
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
29
2.1 the beginning, literature data about com-

Introduction parable reactions are very helpful. A wide
overview about reported electroorganic re-
The success of an electrolysis process actions is given as a basic information
depends on the choice of a suitable source in the following chapters.
electrochemical cell and optimal operation The considerations, prior to beginning,
conditions because there is a widespread must include special characteristics of elec-
variety of electrolyte composition, cell trochemical reactions and their practical
constructions, electrode materials, and consequences in a preparative scale elec-
electrochemical reaction parameters. trolysis:
The objective of this chapter is to study
some essential practical aspects, which • The first fundamental decision is to use
have to be considered. First, as neces- one of the following alternatives
sary background information, the different
alternatives for electrochemical cell opera- – direct electroorganic reaction at an in-
tion are discussed in general. Then follows ert or electrocatalytic active electrode
an overview of properties of electrode ma- surface, which needs no additional
terials, electrolyte components, and cell agent in the electrolyte,
separators. Finally, examples of cell con- – indirect electrolysis, that is, the elec-
structions are shown. trochemical regeneration of a conven-
A precondition for an appropriate de- tional oxidizing or reducing agent,
cision in the planning of a preparative – application of a ‘‘mediator’’, which is
electroorganic synthesis is sufficient infor- present like a homogeneous catalyst
mation about the electrochemical reaction. and is continuously regenerated in
As far as possible, knowledge about the situ at an electrode (see Chapter 15).
influence of parameters such as tempera-
ture, solvent, pH value, and stirring rate Many examples of these ways are
should be included. Electroanalytical stan- shown in this volume, discussing their
dard methods to acquire such data have advantages and drawbacks.
been discussed in Chapter 1: cyclovoltam- • The principle of electrochemistry is
metry as an especially valuable tool and its to replace the direct electron transfer
combination with the rotating disk elec- between atoms or molecules of a con-
trode method for additional knowledge. At ventional redox reaction by separating
the oxidation at the anode and the re- 2.2

duction at the cathode. Even though Target and Scale of the Investigations
in most cases only one of these re-
actions is intended (at the ‘‘working Prior to beginning it is necessary to eval-
electrode’’), the other one unavoidably uate the aim and the scale of the planned
has to be carried out (at the ‘‘counter investigations because many particular
electrode’’), at least without detrimen- aspects, discussed in this chapter, are de-
tal effects on the desired reaction. In pendent on this decision. There may be a
consequence, the selection of optimal wide range of intentions for preparative
electrode materials and of a suitable electrolysis investigations, demonstrated
cell – undivided or divided by a sepa- here by two borderline cases:
rator – will be essential. Recent develop-
• If the target is to find new electrochemi-
ments aim at conversions that produce
cal conversions – perhaps of expensive
useful products simultaneously at the
compounds – then the products only
anode and cathode (‘‘paired electroly-
have to be accessible in small amounts
ses’’, see Chapter 3).
for their identification. A high yield con-
• A typical advantage of electrochemistry
cerning the reactants is required but
in comparison to conventional chemi-
technical aspects such as energy con-
cal reactions is the possibility to control
sumption are not interesting. In this
the reaction by electrical parameters.
case, a small volume will probably be
The choice of the alternatives using a
the most important feature of the elec-
constant cell current (galvanostatic op-
trochemical cell.
eration) or using a constant electrode
• If the investigations are intended to de-
potential (potentiostatic operation) gen- velop an industrial production, the focus
erally has a significant influence on the will be to optimize the operation condi-
results of electroorganic syntheses (see tions and to get base data for scale-up.
Sect. 2.3.2.2 and 2.3.2.3 and Chapter 3). In this case, the electrochemical prop-
• An electrochemical reaction needs the erties of the experimental cell have to
transfer of ions between the electrodes. be equivalent with the planned techni-
Therefore, the solution in the cell re- cal cell. Thus, it is necessary to carry out
quires usually at least minimal ion experiments on a sufficient large scale,
conductivity. In most cases, a support- including lifetime tests of cell compo-
ing electrolyte has to be added, and nents. For industrial and engineering
after the reaction it is separated and aspects, see for example, [1, 2, 3b, 4]
reused. (overview), [5c] (detailed), and [6, 7] (in-
• Electrochemical reactions proceed, in cluding theory).
principle, heterogeneously at the elec-
trode surfaces. Hence, the mass transfer For numerous research intentions, an
has a major influence, especially on average scale will be chosen, considering
the selectivity of the electrode reactions. on the one hand, the costs of chemicals
Therefore, the mixing conditions in the and on the other, the easier experimental
cell have to be optimized, considering work and better reproducibility of results,
also the operation mode as batch or as using a cell of medium – but not too
flow-through reactor. small – dimensions.
2.3 Principles of Electrochemical Cell Operation 31
2.3 2.3.2
Principles of Electrochemical Cell Operation Controlling of the Electrochemical Reaction
Rate by Electrode Potential and Cell Current
2.3.1
Essential Definitions for Electroorganic For choosing a suitable cell construction
Reactions and optimal reaction conditions in the cell,
it is inevitable to consider the fundamental
Fundamental criteria to evaluate the re- correlations between electrode potential
sults of any organic synthesis are the and cell current and their influence on
‘‘yield’’, being the fraction of the entire selectivity and yield of the electrochemical
supplied reactant, which has formed the reactions. Therefore, a simplified overview
product, and the ‘‘selectivity’’, being the is given here. The detailed theory is
fraction of the converted reactant, which elucidated in Chapter 1.
has been used to generate the product. The electrochemical reaction rate and
In addition, the ‘‘current efficiency’’ thus the speed of production in the cell
(‘‘current yield’’) is typical for an electroly- are proportional to the cell current. The
sis process, the fraction of the electrical cell current density – the cell current divided
current – or (integrated over the time) the by the electrode area – is dependent on the
fraction of the transferred charge – which potential of the working electrode.
is used to form the product. The theoret- To achieve a large production rate, the
ical charge transfer for one mol product current density should be as high as possi-
is given by the Faraday constant F , the ble. Particularly, industrial cells need a sat-
charge of one mol electrons, F = 96 485 isfactory current density and ‘‘space–time
As/mol = 26, 8 Ah/mol, multiplied by the yield’’, that is, production per time and cell
number of transferred electrons. volume, because the investment costs and
Of general importance for reactions consequently the production costs are en-
is the ‘‘degree of conversion’’ (short: larged with increasing electrode area and
‘‘conversion’’), being the fraction of a cell volume. But, naturally, the current
reactant that has been removed because of density is limited by different reasons that
the reaction. Because the concentrations have to be considered.
of reactants are decreased and that of
products increased with rising conversion, 2.3.2.1 General Correlations between
the selectivity of the desired reaction Electrode Potential and Current Density
mostly becomes smaller during the course Figure 1 shows typical current den-
of the reaction owing to a decrease of sity–potential curves of an electroorganic
the desired reaction of the reactants and reaction. In this example, the thin line
enhancement of consecutive reactions of represents the anodic oxidation of the
the products. electrolyte without reactants at a higher
If the reaction conditions are changing potential, here at more than 0.8 V versus
with time, (especially during batch oper- NHE. If the reactant 1 is present, it can
ation, see Sect. 2.3.4), it is necessary for be converted according to the thick com-
yield, selectivity, and current efficiency to pact lines at lower potentials above 0.2 V
distinguish between the actual values and versus NHE, and this selectively can oc-
the summarized (integrated) values from cur up to 0.5 V versus NHE. Over 0.5 V
the start to the end of the reaction. versus NHE also, an additional reactant
100
Reactant 2
90 constant
concentration C2
80
C2
70
C2
Current density
60
tion
[mA cm−2]
Reactant 1 C2
decomposi
50 changing
concentration C1
40
C1
30
Electrolyte
2/3 C1
20
1/3 C1
10
0
0 0.2 0.4 0.6 0.8 1 1.2
Electrode potential
[V versus NHE]
Fig. 1 Current density–potential curves for the anodic oxidation of
two various reactants and finally of the solvent. The electrode potential
is measured against a ‘‘reference electrode’’ (RE), here for example,
the ‘‘normal hydrogen electrode’’ (NHE).
2 can be oxidized, increasing the current F = Faraday constant). The equilibrium

consistent with the thick dotted lines (a potential E is dependent on the tempera-
constant concentration of reactant 2 is as- ture and on the concentrations (activities)
sumed). An analogous correlation has to of the oxidized and reduced species of the
be considered for the counter electrode reactants according to the Nernst equation
(here the cathode). (see Chapter 1). In practice, electroorganic
conversions mostly are not simple re-
versible reactions. Often, they will include,
2.3.2.1.1 Equilibrium Potential The min-
for example, energy-rich intermediates,
imum potential, which is necessary to
complicated reaction mechanisms, and ir-
perform a (reversible) reaction, is the equi- reversible steps. In this case, it is difficult to
librium potential E, defined for zero cell define E and it has only poor practical rele-
current. It is typical for a given reaction. By vance. Then, a suitable value of the ‘‘redox
definition, it is related to the NHE, which potential’’ is used as a base for the design
represents the potential zero. If the elec- of an electroorganic synthesis. It can be es-
trode reaction is coupled with the reaction timated from measurements of the ‘‘peak
2 H+ + 2e− H2 at the NHE, theoreti- potential’’ in cyclovoltammetry or of the
cally E can be calculated using the free ‘‘half-wave potential’’ in polarography (see
reaction enthalpy G (Gibbs energy) of Chapter 1). Usually, a common RE such
the total reaction divided by the charge as the calomel electrode is applied (see
transfer of the reaction: E = −G/(z · F ) Sect. 2.5.1.6.1). Numerous literature data
[V] (z = number of transferred electrons, are available, for example, in [5b, 8, 9].
2.3.2.1.2 Overvoltage To obtain a cell only by diffusion and not by convection

current, an ‘‘overvoltage’’, a potential (see Chapter 1). Usually, these concentra-
difference additional to the equilibrium tion differences increase proportional to
potential, has to be applied. Thus, the the current density, according to the first
overvoltage – consisting of different com- Fick’s law.
ponents – is the deciding parameter to
control the speed of an electrochemical 2.3.2.1.3 Limiting Current Density The
reaction. The energy demand due to the diffusion overvoltage hinders the current
overvoltages at both electrodes is lost com- density to rise continuously with increas-
pletely as heat. ing potential, especially in case of low
reactant concentrations. The ‘‘limiting cur-
Charge transfer overvoltage The ‘‘charge rent density’’ for a reaction is reached when
transfer overvoltage’’ is necessary to over- the current density becomes equivalent
come the kinetic hindrance of the elec- to the maximally accessible diffusion rate
trochemical reaction, that is, to surpass of a required reactant, see the horizontal
the activation energy of the charge trans- sections of the thick curves in Fig. 1. Here,
fer at the electrode. The current density the reactant concentration at the electrode
increases exponentially with this overvolt- surface tends to zero and the diffusion
age (see the thin line for the electrolyte overvoltage can reach very high values.
in Fig. 1), frequently by a factor of about The limiting current density usually – in
ten with additional 120 mV overvoltage consequence of the first Fick’s law – is pro-
(for one electron in the transfer step; portional to the reactant concentration, as
this is quantified analogous to the Ar- shown for reactant 1 by the different thick
rhenius law of chemical reactions by the compact curves in Fig. 1. Thus, the lim-
Butler–Volmer equation, see Chapter 1). iting current density can be improved by
an increased reactant concentration, for ex-
Concentration overvoltage (reaction over- ample, due to choosing a reduced degree of
voltage and diffusion overvoltage) If a conversion. There are further methods to
significant current is flowing, the concen- enhance the diffusion rate, such as inten-
trations of reactants will be lower and sified stirring (i.e. thinner diffusion layer),
those of products higher at the elec- elevated temperature, and/or reduced vis-
trode surface than in the bulk electrolyte. cosity (i.e. increased diffusion coefficient).
Hence, consistent with the Nernst equa- For the electrolyte decomposition (thin line
tion, the electrode potential is shifted by in Fig. 1), the diffusion overvoltage is neg-
the ‘‘concentration overvoltage’’. Partially, ligible in the considered range of current
it can be caused by slow chemical reaction density due to the excess concentration of
steps before and/or after the charge trans- the solvent, and no limiting current density
fer (‘‘reaction overvoltage’’). Additionally, is observed.
an unavoidable part of the concentration
overvoltage is the ‘‘diffusion overvoltage’’ 2.3.2.1.4 Side-reactions As soon as the
due to concentration differences in the cell current density surpasses the limiting
‘‘diffusion layer’’ that is formed in the elec- current density of one reaction, the
trolyte adjacent to the electrode surface. electrode potential rises until additionally
In this layer, a mass transfer is possible another reaction takes place (in Fig. 1
oxidation of reactant 2, thick dotted lines, 2.3.2.1.5 Possible Problems in Electroor-

finally the oxidation of the electrolyte). ganic Reaction Systems Unfortunately,
Consequently, the current efficiency for electroorganic reactions do not always
the desired product 1 is lowered and display clearly defined potential condi-
the specific energy consumption for the tions, like those in Fig. 1. Typical reasons
production increases (it is additionally may be:
enlarged because of the simultaneously
rising cell voltage). • For many organic reactions, the Gibbs
If there are no detrimental organic side energies are similar and consequently
there are only little differences in the
reactions, a cell current density in excess
equilibrium potentials, which cannot be
of the limiting current density – and as
used to achieve a selective reaction.
result a loss of current efficiency – may
• Frequently, reactions consist of a chain
be acceptable for laboratory scale experi-
of consecutive reaction steps, including
ments. For example, a hydrogen evolution
species, which need a very high energy,
parallel to an electroorganic cathodic re-
for example, energy-rich radical ions.
duction can even be advantageous as it
This causes an effect similar to a large ac-
improves the mass transfer by moving gas
tivation energy, and the overall reaction
bubbles and thus enhances the organic
runs irreversible. A significant charge
cathodic reduction. transfer overvoltage – up to 1 Volt or
But if reactants or products of the desired more – can be observed, which is much
reaction are lost and/or if undesired com- higher than the equilibrium electrode
pounds are formed by side reactions (i.e. potential E. Consequently, the smaller
yield and selectivity will be reduced), it is differences in E cannot be used to
necessary to avoid any overstepping of the run reactions selectively, different from
limiting current density. Especially in case Fig. 1, where large potential differences
of changing conditions (batch operation) are available.
with a rising degree of conversion – here, • Additionally, complicated and only par-
the most significant parameter will be the tially understood influences may be
decreasing reactant concentration – a con- found, for example, of the electrode ma-
tinuous adjustment of the current density terial (possibly including its history) or
is indispensable. Then it will be better to of the electrolyte composition.
work at a constant electrode potential than
at constant cell current (see Sect. 2.3.2.3). Under such conditions – that is, miss-
In the example of Fig. 1, the potential ing clearly separated electrode poten-
differences are so large that clearly dis- tials – concurrent reactions will occur. In
criminated reactions can be realized. At consequence, only a poor selectivity of the
a potential of 0.3 V, only reactant 1 is ac- electrode reactions is to be expected and
tive, even at low concentrations for high well-optimized reaction conditions will be
degrees of conversion. indispensable.
There are also some reactions known,
which need – contrary to the normal 2.3.2.1.6 Overvoltage Due to Electrolyte
case – a high current density for a suffi- and Cell Separator Resistance The dif-
cient selectivity, for example, the Kolbe ferent overvoltages, discussed above, in-
reaction (see Chapter 6). fluence the correlation between electrode
potential and current density. Additional potentials and overvoltages and of the
overvoltages are caused by the resistance of ohmic voltage drops in the electrodes (elec-
the electrolyte and of the separator in a di- tron conductors) and in the electrolytes,
vided cell. Although these overvoltages are including cell separators (ion conductors).
not parts of the electrode potentials, they
have to be surpassed in order to enable a 2.3.2.2 Operation with Constant Cell
current in the cell and they enhance the Current (Galvanostatic Operation)
heat evolution in the cell. They increase lin- Constant current electrolysis is an easy
early with rising current due to the ohmic way to operate an electrochemical cell.
resistance (in case of strong gas evolu- Usually, it is also applied in industrial
tion, the increase may be steeper because scale electrolysis. For laboratory scale
the resistance increases). These overvolt- experiments, inexpensive power supplies
ages can be lowered by taking electrolytes for constant current operation are available
with higher conductivity, for example, sol- (also a potentiostat normally can work in
vents with higher dielectric constants and galvanostatic operation). The transferred
the use of sufficiently dissociated support- charge can be calculated directly by
multiplication of cell current and time (no
ing electrolytes. These overvoltages can
integration is needed).
be furthermore lessened by decreasing
The electrode potentials (exactly the over-
the distance between the electrodes and
voltages) are dependant on the current
by using diaphragms of medium to high
density. Thus, using the galvanostatic op-
porosity (see Sect. 2.4.3.1).
eration mode, optimal results are attained
only if a well-defined current density can
2.3.2.1.7 Cell Voltage Figure 2 shows be chosen with a clear difference be-
schematically the cell voltage as summa- tween desired and undesired reactions,
tion of the above discussed equilibrium as in Fig. 1. This precondition is favored
+
Anode current feeder Ohmic voltage drop
Anode (electron conductors)
potential
Anode
Anodic equilibrium potential

Charge transfer
Overvoltage anode
reaction diffusion
Anolyte
Cell voltage
(possibly increased by gas bubbles)

Ohmic voltage drop
Cell separator (ion conductors)
Catholyte
(possibly increased by gas bubbles)
Charge transfer
Overvoltage cathode
Cathode
potential
reaction diffusion
Cathodic equilibrium potential
Cathode Ohmic voltage drop
Cathode current feeder (electron conductors)
−
Fig. 2 Composition of the cell voltage (not in real scale).

especially at constant concentrations ow- such as concentrations of reactants and

ing to continuous addition of reactant and products, degree of conversion, tempera-
removal of product in a flow-through cell ture, and so on.
(steady state).
For batch operation (see Sect. 2.3.4), the 2.3.2.3 Operation with Constant Electrode
limiting current density is going to zero for Potential (Potentiostatic Operation)
increasing degree of conversion (see reac- As discussed in Sect. 2.3.2.1, electroor-
tant 1 in Fig. 1). Here, the galvanostatic ganic reactions can often be selectively
operation may only be acceptable if exclu- controlled by a constant potential of the
sively unproblematic side reactions occur, working electrode, even at decreasing reac-
such as water electrolysis as solvent decom- tant concentrations (see Fig. 3). A precon-
position. In all other cases, better results dition of this operation mode is a suitable
can be expected using the potentiostatic potential-measuring equipment in the cell
operation (see next section). (special practical aspects of potential mea-
In some problematic cases, there will be surement are discussed in Sect. 2.5.1.6).
no obvious limits available for the choice The optimal potential can be chosen us-
of the current density in galvanostatic op- ing a current density–potential curve (see
eration. Concurrent reactions take place, Fig. 1), available by cyclovoltammetry with
resulting in a poor selectivity. But here a very low scan rate.
the potentiostatic operation also cannot A potentiostat is relatively expensive,
demonstrate its advantages, and proba- especially if high power is needed. A
bly the simpler galvanostatic operation cheaper method is to use the galvanostatic
may be applied. To find relatively suitable operation and to measure continuously
operation conditions, an experimental op- the potential and to adapt the cell current
timization of the current density should be manually (or using a computer data
carried out, perhaps including parameters acquisition system) in order to adjust the
Potentiostat
Control input
Direct
current
mA source
mV
Working electrode
Counter electrode
Reference
electrode
Fig. 3 Scheme of potentiostatic

RE operation for a preparative electrolysis,
using in principle a simplified
cyclovoltammetry equipment. The
potential of the working electrode is
measured by a Luggin capillary, coupled
Diaphragm
with a reference electrode (RE, see

Sect. 2.5.1.6). The control circuit in the
Luggin potentiostat adjusts the cell current until
capillary the potential of the working electrode is
equal to the voltage at the control input.
electrode potential as accurately as possible For instance, graphite has a higher hy-
at the desired value. This technique may drogen overvoltage than platinum and its
be applicable even in cases where it is catalytic activity for hydrogenation is low.
difficult to measure the potential correctly, Thus, a graphite counter electrode may
for example, in nonaqueous solvents of be useful for hydrogen evolution without
poor conductivity. Then, the control circuit further electroorganic reactions. Another
of a potentiostat cannot properly work, but example is the addition of a ‘‘depolarizer,’’
it is much easier to measure than to control which enables an innocuous reaction at
a potential. the counter electrode before an essential
Because the current is not constant compound in the solution can be at-
during the potentiostatic operation, it has tacked. Special depolarized electrodes are
to be integrated during the experiment ‘‘gas diffusion electrodes’’ (GDE), known
for calculating the charge transfer and from fuel cells, or ‘‘sacrificial electrodes,’’
the current efficiency. Coulometers or which are dissolved during the reaction
electronic integrators are commercially (see Sect. 2.4.1.2).
available. If a computer data acquisition A typical counter electrode reaction
system is used, the current integration is is the electrolysis of water. Here the
possible by software. cathodic evolution of hydrogen is coupled
In principle, a further inexpensive with the formation of base, the anodic
method is to work at constant cell volt- development of oxygen produces acid
age. But here the potentials of the working additionally. Frequently, acid and base
and of the counter electrode, and all volt- formation at both electrodes will be
age drops of the electrolytes and of the cell balanced. Otherwise, a buffer solution
separator are included (see Fig. 2). Thus, or a (continuous) base/acid addition, for
in most cases, clearly defined conditions at example, by a pH-controlling system, can
the working electrode cannot be adjusted enable the application of an undivided cell.
using this operation mode (nevertheless, In many cases, it will be impossible to
because of its uncomplicated realization, prevent unwanted reactions at the counter
it is applied in most technical electroly- electrode. Then a separation of the anolyte
ses to achieve approximately the desired and catholyte is needed. An optimal com-
cell current). promise has to be found for the separator
between separation effectiveness and ion
2.3.3 conductivity, that is, minimized electrical
Undivided or Divided Cells resistance and low energy consumption.
Moreover, chemical, thermal, and me-
Because of the low-cost construction and chanical stability and price of the separator
simple operation, an undivided cell is al- have to be considered. Naturally, a com-
ways desired but it cannot be realized in all plete separation is impossible, because a
cases. A precondition for electrolysis in an slight diffusion rate is inevitable. In labo-
undivided cell is that disadvantageous reac- ratory scale experiments, probably a high
tions and reaction products at the counter cell voltage is acceptable in order to realize
electrode can be avoided, for example, by a maximal separation.
selection of the electrode material and/or Two basically different types of cell
of the electrolyte composition. separators are available: porous separators
with unselective ion transport and ‘‘ion- start-up for optimal working. Large-scale
exchange membranes,’’ which support the industrial cells are often operated under
selective transport of either cations or steady state conditions.
anions (see Sect. 2.4.3). Batch operation in a larger scale – in
laboratory or even industrial applica-
2.3.4 tions – frequently is realized using a flow-
Batch Operation or Flow-through Cells through cell with optimized flow charac-
teristics, which is coupled by circulating
Batch operation is the simplest way of pumps with reservoirs that contain the
electrolysis and, therefore, mostly applied reaction solutions.
for electroorganic syntheses. The reac-
tant concentration decreases with rising
degree of conversion (see reactant 1 in 2.4
Fig. 1). The selectivity of the reaction can Components of Electroorganic Reaction
be maintained in spite of a decline of Systems
the limiting current density by potentio-
static cell operation. Usually, the reaction The following short overview can only give
is carried out up to a selected conversion an impression of some usual or innovative
or transferred charge, respectively. Owing cell components and materials (a more
to the continuously changing conditions, detailed overview is given, for example,
much information about the reaction is in [3a, 3b, 10, 11]).
available by analysis of samples, extracted Particular attention should be paid to
in suitable intervals during the exper- toxic materials. Electroorganic synthesis
iment. A plot of all concentrations of will become increasingly of interest in
reactants and products versus time or the preparation of speciality chemicals,
transferred charge gives information about for example, food additives and pharma-
reaction rate, yield, selectivity, current ef-
ceuticals. Thus, toxic materials should be
ficiency, and also about any by-product
avoided as far as possible, for example, for
formation in parallel and/or consecutive
electrodes, solvents, or supporting elec-
reactions.
trolytes. At least, it has to be guaranteed
Constant process conditions – as well
that toxic materials in the products can
of concentrations as of other parame-
ters – are realized using a flow-through be separated or removed below the official
cell in steady state operation. Into the threshold values.
cell continuously reactants are added and Precondition of a successful electroor-
products are removed to maintain constant ganic synthesis is an optimal arrangement
concentration and conversion. Additional of all incorporated components. Therefore,
expenses, especially pumps, are needed, all available information from literature,
however. This continuous operation will supplemented, if possible, by results of
be applied, for example, if optimal results own experiments, should be considered.
only are achievable using well-defined pro- The best way to get actual informa-
cess conditions. Another example is the tion about suppliers of materials and
application of cell components – such as equipment – that probably may be very
ion-exchange membranes – that need con- quickly changing – is the Internet via a
stant concentrations and a long time after search engine.
2.4 Components of Electroorganic Reaction Systems 39
2.4.1 subsequent chemical reactions. All these

Electrodes steps, and consequently the selectivity
of the reactions, will be influenced by
The electrodes are the typical and most properties of the electrode surface, for
important components of an electrochem- example, by chemical composition, mor-
ical cell – especially the working elec- phology, and porosity, which may also be
trode – which usually decide about the dependent on the history of the electrode.
success of an electroorganic synthesis. Usually, there is a significant interdepen-
Electrode materials need a sufficient elec- dency between the electrode properties and
tronic conductivity and corrosion stability the electrolyte composition, that is, reac-
as well as, ideally, a selective electrocat- tants, products, solvents, and supporting
alytic activity which favors the desired electrolytes, including impurities.
reaction. The overvoltages for undesired This shall be elucidated by two exam-
reactions should be high, for example, for ples for the influence of the electrode
the decomposition of the solvent water material on the product spectrum of well-
by anodic oxygen or cathodic hydrogen known electrochemical reactions [4], see
evolution. But, additionally, the behav- Scheme 1 below.
ior of electrodes can show unexpected A special problem can be the passiva-
and incomprehensible effects, which will tion of the electrode surface by insulating
cause difficulties to attain reproducible layers, for example, formation of oxides
results. on metals at a too high anodic poten-
The electrode reaction typically in- tial or precipitation of polymers in aprotic
cludes a lot of steps, such as adsorp- solvents from olefinic or aromatic com-
tion and desorption, one or several elec- pounds by anodic oxidation. As a result,
tron transfer steps, preceding, and/or the effective surface and the activity of the
• Anodic oxidation of carboxylates in aqueous solution via decarboxylation
Pt smooth
[R •] R−R (Kolbe reaction) [12, 13]
In water PbO2
R−COO− R′−OH, CO, CO2
−e−, −CO2
Graphite
[R+] Resulting products [14]
• Cathodic reduction of acrylonitrile in aqueous solution

Pt, Ni
CH3−CH2−CN (via Had) [15]
Hg, Pb, C, Cd NC−(CH2)4−CN

and CH3−CH2−CN
In water [16]
CH2=CH−CN via
+e−
Pb CH2=CH−CH2−NH2 [CH2=CH−CN]•−
Strongly acidic [17]
Sn Sn(CH2−CH2−CN)4
[18]
Scheme 1 Influence of the electrode material on the product spectrum of an electrochemical
reaction.
electrode are diminished. To avoid an in- about electrodes is given, for example,
creasing of the local current density and in [10, 11].
consequently a reduced reaction selectiv-
ity, the cell current should be decreased 2.4.1.1 Examples of Electrode Materials
(automatically achieved by potentiostatic
operation). A periodical change of the po- 2.4.1.1.1 Anode Materials: General Re-
larity of the electrodes for regeneration of quirements A major problem and thus
the activity can be helpful (then a sym- a decisive factor for the choice of anode
metrical construction of the cell will be materials is corrosion, except when the dis-
suitable). Also, additives to the electrolyte solution of a metal is the desired reaction
with better dissolving power for polymers (‘‘sacrificial anodes’’, see Sect. 2.4.1.2.4).
can be beneficial. The stability of anode materials is ex-
Electrodes may consist of a homoge- tremely dependent on the composition of
neous material – frequently, with an in the anolyte (e.g. pH value, aqueous or non-
situ formed active layer on the surface – or aqueous medium, temperature, presence
of a carrier material with an active coat- of halogenides, etc.).
ing. A proper connection to the current In aqueous electrolytes, frequently the
feeder and a suitable assembling of the oxygen overvoltage is an essential aspect.
cell must be enabled; often, a leakproof If the anode is the working electrode and a
installation of electrodes in the cell body is strong oxidation power is desired, special
required. Therefore, the mechanical prop- materials with a high oxygen overvoltage
erties of the electrode material have to pass are needed in order to reduce concurrent
practical selection criteria: oxygen production. If the anode is the
oxygen evolving counter electrode it is
• strength, hardness, elasticity, brittle-
mostly difficult to avoid disadvantageous
ness, and so on.
oxidation reactions, due to the high
• possibility to be converted to wires,
potential of the oxygen formation, further
sheets, grids, expanded metal sheets,
increased by the oxygen overvoltage. There
porous plates, such as sintered metal,
are no anode materials with a real low
felt, or foamed material, and so on.
oxygen overvoltage. Thus, in most cases,
• possibilities of cutting, machining,
the anode as counter electrode has to
welding, or soldering, and so on.
work in a divided cell within a separate
A very important aspect is corrosion, compartment, unless a depolarized anode
concerning a possible contamination of can be used (see Sect. 2.3.3).
electrolyte and products – particularly in
case of toxic materials – and with respect 2.4.1.1.2 Cathode Materials: General Re-
to the electrode lifetime. Last, not least, quirements Cathodes usually have no
the price can be decisive, especially if a corrosion problem. If the cathode is the
commercial application is planned. working electrode, a main selection cri-
In the following section, examples terion of the materials is the hydrogen
of electrode materials for application overvoltage, that is, the accessible reduc-
as anode and/or as cathode, and then tion power, which may vary in a wide range
some electrode types of practical interest (e.g. hydrogen overvoltage at 1 mA cm−2
are discussed. A comprehensive overview very low ηH < 0.1 V: Pt, platinum metals;
low ηH < 0.2 V: Ni, Au; medium ηH which can be overcome by alloying with
0.2–0.6 V: Cu, Ag, Fe, Al, Ti, Cr, Mo, W, ruthenium [19].
Bi, stainless steels (Cr-Ni-Fe), brass (Cu- Anodic corrosion in case of platinum
Zn), Monel (Cu-Ni); high ηH ≈ 1.0 V: metals mostly is insignificant or at least
Hg, Pb, Cd, Sn, Zn, graphite) [4]. A princi- small for most anolyte compositions and
pally high hydrogen overvoltage of a pure conditions. But it may be an economic
cathode material can be decreased – that problem for industrial applications. Fur-
is, the cathode will be poisoned and hydro- thermore, as aforementioned, it can be the
gen evolution occurs – even by very small reason of cathode poisoning. The corro-
amounts of other metals, for example, dis- sion rate of gold, and especially of the less
solved from a noble metal anode (this has noble metals, is very dependent on the pH
to be considered in the selection of the value of the anolyte.
anode material).
A further argument for the choice of the Cathode Platinum metals, especially
cathode material may be the catalytic activ- platinum and palladium, achieve the
ity for hydrogenation reactions. Vice versa, lowest known overvoltages for hydrogen.
this is also important if the cathode is the Moreover, they are effective catalysts for
counter electrode – usually evolving hy- hydrogenation reactions [15].
drogen – where hydrogenation reactions
are undesired.
2.4.1.1.4 Nickel
2.4.1.1.3 Platinum, Platinum Metals or Anode A nickel anode forms in aqueous

their Alloys, and Other Noble Metals Plat- alkaline solutions a layer of Nickel(III)-
inum, platinum metals or their alloys, oxide NiOOH. Owing to its application in
and other noble metals are classical elec- nickel cadmium and nickel metal hydride
trode materials, and much literature about accumulators, it is much investigated [20].
these is available. Though the orientation It is stable for oxygen evolution and very
of single crystals has a considerable in- interesting for selective oxidation reactions
fluence, for synthetic applications, only ( [21] see Chapters 6, 15), an industrial
polycrystalline materials are suitable. The application is one step of the vitamin C
metals show significant differences in their production [22]).
electrocatalytic and additionally in their
chemical catalytic activity. Owing to the Cathode Nickel may be an alternative
high price of the metals, it may be inter- for platinum metals in alkaline solutions
esting to use them as a coating on a carrier due to its low hydrogen overvoltage and
(see Sect. 2.4.1.1.10). catalytic activity. The activity is especially
high at the very fine dispersed ‘‘Raney
Anode Investigations using cyclovoltam- nickel’’, which is available from a layer
metry confirm an important effect of of a nickel alloy on the cathode surface
surface oxides (see Vols. 3, 4). A known by dissolving the alloy metal (aluminum
example of the different anodic activity is or zinc) in alkaline solution prior to use
the poisoning of platinum by adsorbed (e.g. [23, 24]. Raney nickel usually is not
carbon monoxide species, for example, stable against oxygen and self-ignition in
in the direct methanol fuel cell (DMFC), air may be possible).
2.4.1.1.5 Iron, Stainless Steel The corrosion rate of PbO2 – often en-
hanced by mechanical erosion – is rela-
Cathode Iron is a very cheap cathode tively high and may be a problem due to
material with a relatively low hydrogen the toxicity of lead. PbO2 can be stabilized
overvoltage (e.g. [25]). It is of interest by modification with, for example, silver,
for industrial applications. In order to antimony, tin, cobalt oxides (or by alloying
avoid corrosion during interruption of the of the lead base metal with these metals,
current, stainless steel may be suitable, respectively) [29].
especially in laboratory cells where the in-
creased electrical resistance and hydrogen
Cathode The hydrogen overvoltage on
overvoltage are irrelevant.
lead is especially high, but this can be real-
ized only with very pure lead. Other metals
2.4.1.1.6 Lead About lead much litera- with a lower hydrogen overvoltage must
ture is available due its technical applica- not be present, for example, in the elec-
tion in the ‘‘lead-acid-battery’’. Pure lead trolyte or from the anode. In the negative
is very soft and has a poor mechanical sta- electrode of lead-acid-batteries, antimony
bility. Therefore, often it is applied as a as alloying metal is replaced with calcium
coating on a carrier or alloys are used, for in order to achieve a high hydrogen over-
example, with antimony (‘‘type metal’’). voltage (‘‘maintenance-free battery’’) [30].
Anode (lead dioxide) On lead as anode 2.4.1.1.7 Mercury

material in aqueous solutions (for exam-
ple, [26]) usually a lead dioxide layer is Cathode Mercury is a classical cathode
formed and continuously regenerated at material for electroorganic reductions due
high anodic potentials, but in longer oper- to its extraordinarily high hydrogen over-
ation the lead is destroyed by this process. voltage in aqueous solutions. Because it is
PbO2 is an anode material with a very liquid, it needs special cell constructions
high oxygen overvoltage and therefore it (see e.g. Fig. 8). By stirring, its surface can
offers a high anodic potential and a strong be continuously renewed so that reduced
oxidation effect in aqueous acidic solu- metals – including even alkali metals from
tions, especially in sulfuric acid (industrial a supporting electrolyte – will be dissolved
utilization e.g. for chromic acid regenera- as amalgam and thus will not decrease the
tion [27]). Because PbO2 is a strong chem- hydrogen overvoltage at the surface. For
ical oxidation agent too, its application as many applications also, an amalgamated
anode material is restricted if a sponta- metal electrode such as copper, which is
neous reaction with a reactant is possible. easier to handle, may be sufficient. The
PbO2 is also applicable as a coat- toxicity of mercury restricts its applicability
ing on a suitable carrier material (see for technical syntheses.
Sect. 2.4.1.1.10). PbO2 -coated titanium an-
odes with good stability are commercially 2.4.1.1.8 Carbon Carbon is a common
available. On platinum or platinum-coated electrode material (e.g. [31]) that is much
titanium a coating of PbO2 for laboratory cheaper than noble metals. Its conductivity
use can easily be prepared electrochemi- is by a factor of about 100 lower than that of
cally (e.g. [28]). metals, but this will be no problem using
suitable electrode constructions. Its tech- machining (diamond tools necessary). It is

nical applications include current feeders additionally available as a foamed material.
of batteries, anodes for chlorine evolu- Carbon- or graphite-filled polymers or
tion, bipolar electrodes for industrial scale a carbon paste, which can easily be
electroorganic syntheses (see Fig. 12), and regenerated by removing a surface layer,
anodes in the molten-salt electrolysis for are also possible electrode materials.
aluminum winning. Generally, carbon materials show a low
Carbon is available in a large variety electrocatalytic activity. But often it is very
of qualities. Electrode carbon is produced dependent on the history of the electrode,
with different percentages of crystalline for example, due to removing of a surface
graphite (as a consequence, for example, coverage or due to roughening of the
different conductivities and stabilities are surface. Thus it may be difficult to get
resulting). It is usually highly porous and reproducible results, and frequently a long
not leakproof against gases and fluids. time of changing conditions after start of
It can also be impregnated with resins, the electrolysis is observed.
even using fluorinated resins, in order to
realize tight materials of high chemical
Anode In aqueous anolytes, under con-
stability. All these materials can be easily
ditions which favor the oxygen evolution,
machined but their solidity is limited and
carbon is attacked under carbon dioxide
they are somewhat brittle. Graphite fiber
formation, this is increasingly encoun-
reinforced graphite with a very high me-
tered with more porous materials. Glassy
chanical strength is obtainable for special
carbon will be relatively stable. A low pH
applications (e.g. SGL-Carbon Group).
value may retard the oxygen reaction, but
Graphite is offered moreover in flexible
carbon remains a problematic anode ma-
sheets (e.g. Sigraflex of the SGL-Carbon
terial in aqueous solutions. Additionally,
Group). This is primarily a sealing mate-
it can be attacked because of intercalation
rial, but it is suitable also as electrode or
of anions.
corrosion resistant current feeder (erosion
In nonaqueous media, carbon (graphite)
in case of gas evolution is possible).
frequently is an optimal anode material,
Carbon fiber or graphite fiber materials,
for example, for methoxylation reactions,
available, for example, as felt, clothes, or
even in an industrial scale (capillary gap
paper, and so on, are state of the art
cell, see Fig. 12). It shows an appreciable
for realizing conductive diffusion zones
overvoltage for the oxidation of methanol
in fuel cells but also they can be used as
compared to platinum.
electrodes. They attain a very high porosity
(free space volume up to 80%) and a
surprisingly good elasticity. Cathode The hydrogen overvoltage of
Glassy carbon (vitreous carbon) is a carbon is relatively high. Thus, if the
further modification. It is a smooth and cathode is the working electrode, a lot
tight material of high corrosion resistance of reduction reactions is enabled. On
and for many reactions it may be a the other hand, the catalytic activity
suitable alternative of platinum. It is for hydrogenation reactions is low. This
relatively expensive, but much cheaper is advantageous if the cathode is the
than noble metals. It is very hard and brittle counter electrode: cathodic side-reactions
and allows only limited possibilities for are avoided besides hydrogen evolution,
and therefore carbon can be a useful applications especially metals such as

cathode material, even though the energy titanium are appropriate.
consumption is increased because of the
hydrogen overvoltage. Titanium as a carrier metal Titanium (or
a similar metal such as tantalum, etc.)
2.4.1.1.9 Ceramic Materials An example cannot work directly as anode because
of a sufficiently conductive metal oxide is a semiconducting oxide layer inhibits
magnetite Fe3 O4 , which has been used, for any electron transport in anodic direc-
example, in the past as corrosion resistant tion (‘‘valve metal’’). But coated with an
anode material for industrial chlorine electrocatalytic layer, for example, of plat-
evolution (it can be smelted and casted inum or of metal oxides (see below), it is
at 1500 ◦ C, but it is a very brittle material). an interesting carrier metal due to the
The modern material Ebonex is a excellent corrosion stability in aqueous
mixture of substoichiometric titanium ox- media, caused by the ‘‘self-healing’’ passi-
ides Ti4 O7 , Ti5 O9 . . . Tin O2n−1 (‘‘Magnéli vation layer (e.g. stability against chlorine
phases’’ [32]). It offers a unique combina- in the large scale industrial application
tion of electrical conductivity and corrosion of ‘‘Dimension Stable Anodes’’ DSA ,
resistance. Primarily, Ebonex is produced see below).
as a powder. As is usual for ceramics, A cathodic current is in principle pos-
the ready-formed material is hard and sible, but in case of hydrogen evolu-
brittle, the possibilities of machining are tion, titanium will be destroyed by hy-
restricted (diamond tools). dride formation.
The electrocatalytic activity of Ebonex Protection layers between the titanium
is low, the overvoltages for oxygen and metal and the electrocatalytic coating,
for example, of substoichiometric tita-
hydrogen are very high. Additionally, to
nium oxides (see Ebonex above), increase
its direct application as electrode material,
the stability by shielding the metal, for
it is an interesting carrier material for
example, to avoid the formation of in-
electrode coatings. Even very thin layers of
sulating titanium dioxide layers on the
the coating show only the electrochemical
metal [35]. The preparation of such elec-
properties of the coating but not of the
trodes with optimal properties usually
carrier [32–34].
needs the special know-how of commercial
suppliers.
2.4.1.1.10 Coated Electrodes and Carrier It has to be considered that tita-
Materials Numerous interesting elec- nium – at least without special protec-
trode materials are applicable exclusively tion layers – will be attacked by several
in the form of a coating on a carrier ma- chemicals: for example, fluorides, fluorine-
terial. Besides the electrocatalytic coatings containing substances, such as tetrafluo-
listed below the use of precious metal elec- roborates BF4 − , or oxalates, and possibly
trodes as a thin layer on a cheaper carrier by other organic acids, which may be
material will be attractive. formed during anodic oxidation reactions.
Common carrier materials will be, An application of titanium in nonaqueous
for example, carbon, glassy carbon, or media is not suitable (instability of the
Ebonex , but for practical and industrial passivating oxide layer).
Metal oxide coatings Commercial lead The application of a DSA for elec-
dioxide coatings, for example, on titanium, troorganic oxidations [39] may possibly be
have a higher stability compared with disturbed because of corrosion of the ac-
lead or lead alloy anodes with their in tive layer and/or the titanium carrier by
situ formed oxide layer. A secure contact organic reactants and products. If signifi-
between PbO2 and titanium has to be cant advantages using a DSA are expected,
guaranteed, for example, by a platinum stability tests of the DSA under the special
layer or at least by a sufficiently large conditions have to be performed.
number of platinum crystallites. Analogous to the DSA manufacture,
Also, other metal oxide coatings are pos- a pure titanium dioxide coating can be
sible, for example, electrochemically de- prepared, which shows a high activity and
posited manganese dioxide. Moreover, fur- stability (also against titanium hydride
ther electrocatalytically active oxides are reformation), for electroorganic cathodic
search objectives, for example, oxides with reductions (e.g. [40], see Chapter 7).
spinel structure such as CoMn2 O4 [36].
Diamond coating (boron doped) A new

Dimension stable anodes (DSA ) These unconventional electrode material with
titanium anodes with platinum metal ox- very interesting properties is diamond,
ide coatings have revolutionized the in- electrically conductive by doping with
dustrial chlor-alkali electrolysis [37] (about boron (e.g. [41, 42]). It can be applied
10% energy saving compared to graphite
on various carriers – for example, silicon,
anodes that corrode continuously by oxy-
carbon, tantalum, titanium – by chemical
gen/carbon dioxide formation). Ruthe-
vapor deposition (CVD). It has a low
nium as active catalyst metal – with its easy
catalytic activity and the highest known
Ru4+ /Ru3+ changing for the oxidation
overvoltages for oxygen and also a high
of chloride ions to chlorine – is optimally
one for hydrogen evolution. Therefore, the
fixed in an electrically conductive mixed
potential range and the electrochemical
crystal structure with titanium dioxide. A
power for oxidation as well as for reduction
simple DSA for laboratory use is easy
to prepare according to [38] (example I: is extraordinarily high. A possible applica-
painting and thermal decomposition of a tion is the electrochemical detoxification
solution of RuCl3 · xH2 O, a titanium alco- of waste (e.g. [43, 44]).
holate and HCl). But DSA’s of optimized
stability, including the above-mentioned 2.4.1.2 Examples of Electrode Types and
protection layers, are only available from their Special Properties
commercial suppliers (complex coating
compositions and production processes, 2.4.1.2.1 Smooth or Porous Electrodes
for example, plasma spraying too, at exactly The porosity of an electrode surface will
defined conditions). significantly influence its electrochemical
Ruthenium will be dissolved by oxygen behavior, especially because of a consid-
evolution (volatile RuO4 ). Coatings based erable decrease of the effective current
on iridium/tantalum oxides are stabile density in case of materials with a high
for oxygen evolving anodes, even with microporosity and consequently a large
simultaneous chlorine evolution in the effective surface area. A well-known exam-
presence of chlorides. ple is platinized platinum that can enable
reactions that are impossible at smooth formation of gas at both electrodes in di-
platinum. A similar material is Raney vided cells, mostly vertical electrodes will
nickel. But also a simple roughening of an be necessary. Then a possible decrease of
electrode surface, for example, by etching, the current density in the upper part of the
may be advantageous. cell has to be considered (see Sect. 2.5.1.1).
Dimensions and structures of pores
in electrode materials will vary in an 2.4.1.2.3 Gas Diffusion Electrodes Gas
extremely wide range. The influence of diffusion electrodes (GDE’s) are well
the porosity on the electrode properties known from fuel cells, for example, [47].
includes also mass-transfer effects. The function of gas consuming GDE’s is
In order to extend the effective electrode based on ‘‘three phase zones’’, where the
area in principle three-dimensional elec- gas, the electrolyte and the electrocatalyst,
trodes are possible, for example, by using that needs a sufficient electrical connection
a packed particle bed, a sintered or foamed to the current feeder, are simultaneously
metal, or a graphite fiber felt. But the depth in contact. The electrocatalyst, usually plat-
of the working electrode volume usually is inum metals, should be located in the three
only small (it is dependent on the ratio of phase zones, realizing a maximal surface
the electrode and electrolyte conductivity, that is the effective electrode area. A dupli-
for example, [45]). cate pore system must be established: on
the one hand, for the electrolyte, usually
by hydrophilic carbon black, which is also
2.4.1.2.2 Gas Evolving Electrodes Gases,
the electronically conducting carrier of the
for example, hydrogen, oxygen, or carbon
catalyst, and, on the other hand, for the
dioxide, are often formed in the main
gas, typically by addition of hydrophobic
reaction or as a by-product (caution: the
polytetrafluoroethylene (PTFE). In conse-
possibility of explosive gas mixtures and of
quence, common GDE’s only can work in
an ignition by a shortcut between the elec-
aqueous electrolytes without components
trodes has to be taken into consideration). that impede the hydrophobic rejection of
An advantageous effect of the moving gas the electrolyte from the gas pores.
bubbles is the increase of the mass transfer GDE’s may be interesting for synthesis
at the electrode surface [46]. On the other cells as depolarized electrodes (e.g. [48]). A
hand, the gas has to be removed as fast as hydrogen-consuming anode will work at a
possible from the current path in front of low potential that avoids undesired anodic
the electrode, in order to prevent a too large oxidations (e.g. no chlorine evolution in
decrease of the electrolyte conductivity and presence of chlorides). In order to reject
a perturbation of the uniform current den- an excess of the electrolyte from the GDE
sity on the electrodes, up to a (temporarily) structure, a proton-conducting membrane
blocking of the electrode surface. Espe- (Nafion ) between the GDE and the
cially big gas bubbles must be avoided. An electrolyte can be used (‘‘Hydrina ’’, De
optimally perforated structure of the elec- Nora Spa. [49]).
trode is desired, for example, expanded A fascinating option is offered by carbon-
metal sheets. A horizontal electrode ar- based oxygen-consuming cathodes, which
rangement can be suitable for undivided can reduce oxygen into hydrogen peroxide
cells or if a gas evolution only is possi- (e.g. [50]). Thus, an oxidizing agent is
ble at the upper electrode. If there is a produced at the cathode! In combination
with the anodic oxidation, a ‘‘200% cell’’ here; a more detailed discussion is avail-
may be possible (e.g. [51, 52]). able, for example, in [3, 5] (comprehensive
data of nonaqueous electrolytes in [56]).
2.4.1.2.4 Sacrificial Anodes A special
type of a depolarized electrode is a 2.4.2.1 Solvents
sacrificial anode – often as counter elec- The significant, often decisive, influence
trode – where the electrode material is of the solvent in chemical reactions simi-
dissolved during the reaction (e.g. [53]). larly is valid for electrochemical reactions
Typical are very electronegative metals, too, for example, due to protic or aprotic
such as magnesium, aluminum, or zinc, and electrophilic or nucleophilic proper-
which avoid – because of their low poten- ties. If an excess of reactants can be used
tial – any anodic oxidation and therefore as solvent, a particularly uncomplicated
allow the application of undivided cells. operation will be possible. An additional
Frequently, this technique is utilized in solvent should be inert. The requirements
nonaqueous media, also in industrial re- for the solvent in dissolving power for
actions (continuous operation in ‘‘pencil reactants and products and the criteria re-
sharpener cells’’, using conic cathodes that garding an easy separation of the products
form a conic shape of the anodes too [54]). from the reaction mixture, for example, the
Ideally, the metal generates a salt that in- boiling point, are comparable for chemical
creases the conductivity of the electrolyte and electrochemical conversions. Gener-
and is not too soluble so that it can be easily ally, there is an interest to use, as far as
removed by precipitation. There are also possible, inexpensive, nontoxic, and easy
conversions where the dissolved anode to handle solvents.
material is used as reactant, for example, But in electrochemistry additional prop-
different metals for production of met- erties of the solvent are essential:
alorganic compounds or sulfur for organic • the ability to solvate ions – dissociated
polysulfides (mixed with carbon powder as cations and/or anions – in order
for sufficient conductivity [55]). to achieve a sufficient conductivity of
the electrolyte (this is often, but not
2.4.2 exclusively, coupled with the polarity of
Electrolytes the solvent),
• an advantageous or at least innocuous
In addition to the function as reaction influence on the electrode reactions,
medium – as in all chemical reactions – in for example, by adsorption at the elec-
electrochemical processes, the electrolyte trode surface – probably in concurrence
has to provide the transport of ions be- to reactants – or by interaction with in-
tween the electrodes. An optimal combina- termediates such as radial ions,
tion of solvent and supporting electrolyte • the usable potential range (‘‘potential
has to be found, considering the reaction window’’) in which the solvent itself
conditions and the properties of reactants, does not react at the electrodes, at
products, and electrodes. A short overview the anode as well as at the cathode
of usual electrolytes – and some examples (in Table 1 a practically acceptable
of unconventional electrolytes as thought- solvent decomposition of 0.1 mA cm−2
provoking impulse for research – is given is assumed, see the thin line in Fig. 1).
Tab. 1 Potential limits of some solvents at 0.1 mA cm−2 and 25 ◦ C [4] sorted according to
increasing dielectric constant ε (with 0.1 m [NBu4 ]ClO4 and platinum electrodes if not otherwise
stated)
Solvent Abbreviation ε Potential limit [V]

Cathodic Anodic
1,2-Dimethoxyethane – 3.5 −3.0a +0.7a

Acetic acid (water free) HAc 6.2 −1.7a +2.0b
Tetrahydrofuran THF 7.6 −3.3c +2.1c
Dichloromethane (methylene chloride) MC 9.1 −1.7 +1.8
Pyridine Py 12.0 −2.2 +3.3
Acetone – 21.0 −1.6 +1.6
Hexamethylphosphoric acid triamide HMPA 30 −3.3c +1.1c
Methanol MeOH 31.5 −2.2a +1.3
N-methylpyrrolidone NMP 32 −3.3a +1.4c
Nitromethane – 35.7 −2.4c +3.0c
Acetonitrile ACN 36.2 −2.6 +2.7
N,N-dimethylformamide DMF 36.7 −2.7 +1.5
N,N-dimethylacetamide DMA 38 −2.6 +1.3
Sulfolane (tetramethylenesulfone) – 44 −2.3a +3.3
Dimethylsulfoxide DMSO 46.6 −2.7 +1.3
Propylenecarbonate PC 65.2 −1.9 +1.7
Water – 80 −2.9a +1.4
85–96 wt-% sulfuric acid – 100 −1.0a +2.1
Tetrahexylammoniumbenzoate (molten at 25 ◦ C) – – −1.2 +0.3
AlCl3 /NaCl/KCl (molten at 150 ◦ C) – – −1.9 +1.0
a Mercury electrode.
b Sodium acetate.
c Lithium perchlorate.
ε = dielectric constant.
2.4.2.2 Supporting Electrolytes But usually an inert supporting elec-

The solute–solvent mixture in electroor- trolyte, which does not react anyway, is
ganic conversions frequently is not con- needed. Important properties for its selec-
ductive enough and a supporting elec- tion are
trolyte has to be added. If an acidic or
basic reaction medium is used, the needed • sufficient solubility and conductivity in
acid or base may be sufficient to increase the applied solvent,
the conductivity of the electrolyte. This • easy separation and recycling,
is an inexpensive way, and after the re-
and similar criteria as for the solvents
action, mostly a simple neutralization is
such as
possible. If in special cases a mediator
is applied – for example, a bromide for • sufficient stability against oxidation and
the industrial anodic methoxylation of fu- reduction (see Table 2),
ran [57] – this can provide an adequate • optimal interaction with the electrode
conductivity. reactions, especially adsorption effects,
Tab. 2 Potential limits of some anions and cations of supporting

electrolytes [4] (concentration 0.1 m in water and acetonitrile at
0.1 mA cm−2 and 25 ◦ C)
Ion Electrode Potential limit [V]

In water In acetonitrile
J− Pt anode 0.30a 0.20

Br− ’’ 0.85a 0.70
Cl− ’’ 1.10a 1.15
F− ’’ (2.6)a,b –
ClO4 − ’’ (1.5) 2.6
[BF4 ]− ’’ – 3.1
[PF6 ]− ’’ – 3.2
Li+ Hg cathode −2.16 −1.8
Na+ ’’ −1.95 −1.7
K+ ’’ −2.03 −1.8
Rb+ ’’ −1.98 −1.8
NH4 + ’’ −2.00 −1.7
N(CH3 )4 + ’’ −2.65 −2.4
N(C2 H5 )4 + ’’ −2.78 −2.5
N(C4 H9 )4 + ’’ −2.87 −2.6
N(C2 H5 )3 H+ ’’ −1.83 –
a Resulting from standard potentials.

b Oxygen evolution already at a lower potential.
• low toxicity, and operation conditions, it may be

• low prize. possible to use the advantages of
an aqueous electrolyte, while avoid-
2.4.2.3 Examples of Electrolytes ing undesired side-reactions. An ex-
ample is the cathodic hydrodimeriza-
2.4.2.3.1 Aqueous Electrolytes Gener- tion of acrylonitrile to adipodinitrile,
ally, water is the first choice as solvent for the largest industrial electroorganic pro-
electrochemistry due to the optimal sol- cess [16]. The best results are ob-
vation of ions in consequence of its high tained with a strongly hydrophobic
dielectric constant. In aqueous electrolytes, cation of the supporting electrolyte (he-
a large variety of suitable salts is available xamethylenebis(ethyltributyl)ammonium
which leads to a high conductivity. Also, phosphate), because it is adsorbed at the
concerning the low costs and the environ- cathode and rejects maximally the un-
mental protection, water will be the most desired hydrogenation to propionitrile in
attractive solvent. But, on the other hand, presence of water [58] (see the reaction
the reactivity of water is relatively high and scheme at the beginning of Sect. 2.4.1).
frequently it obstructs the intended elec- For reactants (solid or liquid), which are
troorganic conversion, forming undesired not sufficiently soluble in water, additional
by-products. cosolvents can be used in order to obtain
Using an optimal combination of sup- a homogeneous solution. Examples are
porting electrolyte, electrode materials, alcohols, such as ethanol or 2-propanol,
and ethers, such as dioxane, but also needed if reactants or especially basic inter-
quaternary ammonium salts as shown in mediates would be protonated by a protic
Table 2 as supporting electrolytes. solvent. Additionally, very high electrode
potentials are accessible (see Table 1). Ow-
2.4.2.3.2 Electrochemistry Using Emul- ing to the small dielectric constant of
sions The electrochemical conversion of aprotic solvents it is difficult to provide
a reactant, which is not sufficiently sol- a sufficient conductivity. The supporting
uble in water, may also be possible in electrolyte has not only to be soluble, but
emulsion, formed by an aqueous elec- must dissociate also into ions. Typical
trolyte and the liquid reactant or an organic compounds are lithium or tetraalkylam-
solvent containing the reactant. This en- monium cations and tetrafluoroborate or
ables to convert compounds with a very hexafluorophosphate anions (perchlorate
low dielectric constant, for example, aro- salts are in principle possible but as ex-
matic hydrocarbons, simultaneously using plosive compounds might be formed their
the high conductivity of an aqueous elec- application is restricted).
trolyte. A ‘‘phase-transfer agent’’ (‘‘phase- Aprotic electrolytes of an adequate high
transfer catalyst’’) such as, for example, conductivity are necessary for lithium bat-
a tetraalkylammonium salt, polyethylene- teries and supercapacitors. Therefore, re-
glycol, or a crown ether, can enhance the cently, much industrial research has been
transport of the reactant between the or- done in this area and highly sophisticated
ganic and aqueous phase (e.g. [59–61]). electrolyte systems have been developed
Also, ultrasound has been used to enhance (e.g. [64]). The supporting electrolytes for
an electrosynthesis in emulsion [62]. aprotic solvents generally are more or less
expensive and toxic. After the reaction,
2.4.2.3.3 Electrolytes Based on Nonaque- their separation and recycling is inevitable
ous Protic Solvents Particularly methanol and frequently needs considerable efforts.
is very often used as solvent. Its high di- A standard aprotic electrolyte sys-
electric constant and general similarity to tem with general applicability for elec-
water enables a good solvation of ions and troorganic syntheses is acetonitrile with
high dissolving power for salts. The low Bu4 NBF4 as supporting electrolyte. It
boiling point simplifies the product separa- shows a wide potential window −2.6 to
tion by distillation. Especially interesting is +2.7 V, a low reactivity (nucleophily and
methanol simultaneously as reactant and electrophily) and a relatively high dielectric
solvent, for example, for methoxylations constant and conductivity. The low boiling
(see Chapter 6). The dual methoxylation, point allows an easy separation after the
for example, of toluene derivatives, re- reaction. The toxicity of acetonitrile has to
sults in the selective synthesis of acetals, be considered, however (maximum allow-
which can be hydrolyzed to aldehydes, unable concentration at the working place
der recycling of the methanol. There are 20 ppm).
various examples of industrial applications The application of aprotic electrolytes
(e.g. [3b, 63]). usually requires that water traces are
carefully removed and therefore needs
2.4.2.3.4 Electrolytes Based on Aprotic much effort for purification steps in
Solvents Aprotic electrolytes are usually an inert gas atmosphere. It has to be
considered that water may be the product in principle, are ion conductors and can
of (side-)reactions at the electrodes. work as electrolyte even in the absence
of a conductive solution. This ‘‘solid poly-
2.4.2.3.5 Molten Salts as Electrolytes In mer electrolyte technology’’ (SPE) actually
the bottom of Table 1, examples of salts is well known for fuel cells (PEMFC =
are shown, which are liquids at room proton-exchange membrane fuel cell and
temperature or at moderately higher tem- DMFC = direct methanol fuel cell) [47].
peratures. Recently, ‘‘ionic liquids’’, for It also enables electroorganic syntheses
example, based on imidazolium salts, without any supporting electrolyte. If the
have found interest as solvents in lab application is possible – a precondition is a
scale reactions (e.g. [65]). In electrochem- sufficient conductivity of the membrane in
istry, they may be used as solvent and the reaction system (see Sect. 2.4.3.2) – the
supporting electrolyte simultaneously. Be- operation is easy and saves expenses for
cause they are not volatile, an easy separating and recycling of a support-
separation from products by distillation ing electrolyte ( [67], overview in [68]).
is possible. Advantages of the SPE technology have
been verified for different reactions using
2.4.2.3.6 Liquefied or Supercritical Gases cation- and anion-exchange membranes in
as Solvents for Electrolytes For very combination with various electrode mate-
special applications, where the increased rials in aqueous and nonaqueous media. A
efforts for low temperature and/or pressur- successful example is the methoxylation of
ized cells are acceptable, liquefied gases, amides, such as N ,N -dimethylformamide
for example, sulfur dioxide or ammonia, (DMF), which runs nearly perfectly with
can be interesting solvents for electrolytes graphite felt electrodes, pressed on the
(see e.g. [3a]). Supercritical fluids show re- surfaces of a cation-exchange membrane
markable properties that are very different (Nafion ) in a pure mixture of methanol
from other solvents. Detrimental to elec- and DMF without any additive. Approxi-
trochemistry is that especially the dielectric mately 100% selectivity and current effi-
constant in the supercritical state becomes ciency at a low cell voltage [68] is better
low. For supercritical carbon dioxide, no than reported for Bu4 NBF4 as supporting
supporting electrolyte with sufficient con- electrolyte [69].
ductivity is known.
Various fluorinations, which need prin- 2.4.3
cipally much energy for the generation Cell Separators
of the reagent fluorine, are carried out
electrochemically in liquid hydrogen flu- As discussed in Sect. 2.3.3, the in principle
oride, even in an industrial scale [66]. desirable application of an undivided cell
Owing to the extreme toxicity and the will be impossible if a reaction at the
corrosive medium, special precautions counter electrode results in unacceptable
are necessary. consequences, for example, impurities of
the product and/or considerable losses in
2.4.2.3.7 Solid Polymer Electrolyte Techno- yield and current efficiency. There is a
logy Ion-exchange membranes, often large variety of cell separators available,
used as cell separators (see Sect. 2.4.3.2), but none of them can work ideally.
The task of a cell separator is to impede a or pottery – with various porosity, pore
direct mixing of anolyte and catholyte and diameter, and thickness. As glass or
to decrease diffusion, but at the same time ceramic diaphragms are rigid and brittle,
the migration of ions has to be possible for adequate mechanical solidity in larger
without a too high voltage drop. Naturally, cells they need an increased thickness,
a compromise of these requirements has causing a high voltage drop. Glass and
to be found. some ceramic materials will be attacked by
The functioning of a separator will be strongly alkaline media.
the more difficult, the more different In aqueous solutions, glass or ceramic
both electrolytes are. With increasing surfaces adsorb OH− ions. Thus, they
concentration gradients diffusion will be are negatively polarized and consequently
enhanced. It can be reduced using a the solution close to the surface is pos-
less porous and/or thicker separator, but itively charged (‘‘ζ -potential’’). Therefore,
then the voltage drop increases. A special in such diaphragms with small pores and
problem, that has to be avoided, is a consequently a large surface, the solu-
precipitation at the surface or within the tion significantly is moved in the electric
separator if the solubility of a compound field towards the cathode. This ‘‘electroos-
is smaller in one solution compared with motic’’ transfer can produce an undesired
the other. transport through the diaphragm.
If for laboratory experiments an optimal Flexible porous diaphragms, available
separation of anolyte and catholyte is also as thin foils, can be applied up to
needed, and a high voltage is acceptable, large dimensions. They can be produced,
two separators can be used. The volume for example, from fiber materials (as paper,
between these can additionally be rinsed felt or woven fabric) or together with a sol-
with a solution for removing compounds uble filler that is subsequently removed. In
that have been transferred through the chemically not aggressive solutions, even
separators but are not allowed to arrive in simple materials such as filter paper or
the opposite cell chamber. regenerated cellulose film (‘‘cellophane’’)
may be usable. Diaphragm materials with
2.4.3.1 Porous Materials very good technical properties formerly
Decisive characteristics of porous sepa- have been made of asbestos, but its applica-
rators (‘‘diaphragms’’) are porosity, pore tion is obsolete due to its danger in causing
diameter, and thickness. For practical use, cancer. Various new alternative materials,
other aspects such as mechanical strength that are asbestos free, are available.
(brittle or flexible), constant dimensions Porous diaphragms are also made of
(swelling in the solvent), and chemical sta- diverse polymers, for example, as sep-
bility are important. arators for batteries. Polymers can be
The mostly applied porous separator in attacked by organic solvents and a swelling
laboratory cells is sintered glass (‘‘fritted of the polymer material may clog a di-
glass’’). It can be simply and leakproof aphragm. The stability of a polymer is
mounted by the glassblower into the walls very dependent on all compounds in an
of glass cells and then it is very easy electrolyte mixture and thus the combina-
to handle. It is available – like similar tion of diaphragm and electrolyte has to
ceramic materials, for example, sintered be carefully selected, especially if a long-
aluminum oxide or unglazed porcelain term application is needed. Diaphragms
of polyethylene or polypropylene are cheap membrane (anion-exchange membrane),

and show a good stability under manifold typically positively charged quaternary
conditions. A universal stability is guaran- ammonium groups are the fixed ions and
teed with polytetrafluoroethylene (PTFE, anions such as Cl− are the counterions.
Teflon , porous diaphragms of this ma- Usually, one of the ions of the supporting
terial are available, for example, from W. electrolyte will be the charge carrier in the
L. Gore & Associates). Owing to the hy- ion-exchange membrane. The selectivity
drophobic properties of these polymers will be nearly 100% in diluted aqueous
it is not possible to use them directly solutions, but it can strongly decrease,
in aqueous solutions. But, if they are depending on the composition and the
wetted previously with an alcohol (e.g. concentration of the electrolytes on both
2-propanol), aqueous electrolytes can be sides of the membrane and additionally be
applied after replacement of the alcohol. influenced by the current density.
An ion-exchange membrane does not
2.4.3.2 Ion-exchange Membranes contain macroscopic pores and the trans-
Ion-exchange membranes are interesting port channels for the migration of ions
as cell separators that are selective for are of molecular dimensions. Neverthe-
cations or anions. They show a high less, as in the case of porous separators,
conductivity, at least in aqueous solutions. diffusion occurs if there are concentra-
But they are not ‘‘simple’’ separators due tion gradients between both sides of the
to their special characteristics, which have membrane. But an additional transport
to be discussed here. effect is typical for ion-exchange mem-
An ion-exchange membrane consists of branes. Because predominantly one type
an ‘‘ionomer,’’ which contains ‘‘fixed ions’’ of ions is mobile, the molecules in the
that are covalently bound to the polymer solvation shells of these ions are com-
backbone. It is electrically neutral because pletely transferred through the membrane.
of included ‘‘counterions’’. If water – or This transport is equivalent to the above-
probably another sufficiently polar sol- mentioned ‘‘electroosmotic stream’’ (here
vent – is absorbed and if the fixed and it cannot be suppressed, not even with a
counterions can be separately solvated to high pressure difference). All uncharged
an adequate degree, the counterions be- compounds such as solvents, reactants,
come mobile and the ion-exchange mem- and products are unselectively transferred.
brane can work as an ion conductor. In a cation-exchange membrane, this
Owing to the electric field of the fixed ions transport is directed to the cathode and
‘‘coions’’ with the same charge as the fixed in an anion-exchange membrane to the
ions are rejected and are typically absent anode. Its quantity is very dependent on
inside the membrane. Thus the membrane the membrane type and on the composi-
is selective for the transfer of counterions tion and concentration of the solutions.
(‘‘permselectivity’’ = permeation selectiv- Up to several molecules per migrating
ity, e.g. [70]). ion can be transferred, that is, a signif-
A cation-selective membrane (cation- icant convective flow through the mem-
exchange membrane) contains negatively brane occurs. Therefore, this effect has
charged fixed ions, mostly sulfonic acid to be considered if the application of ion-
groups, and cations as counterions, for exchange membranes is planned. Possibly,
example, H+ or Na+ . In an anion-selective the electroosmotic stream can be used to
push back an undesired diffusion through allows, using a cell stack with a com-
the membrane. bination of cation- and anion-exchange
Ion-exchange membranes are primarily membranes, to remove or concentrate
designed for aqueous solutions. In organic ionic compounds (salts, acids, bases) in
solvents (e.g. [71]), their swelling may be solutions. In ‘‘bipolar membranes’’, lam-
very strong, perhaps up to dissolution. An- inated layers of a cation and an anion-
other precondition for their use is that the exchange membrane, water can be disso-
solvent is able to solvate the ions inside the ciated into H+ and OH− ions (e.g. [73]).
membrane to permit a sufficient conduc- Therefore, an electrodialysis stack with in-
tivity. In aprotic solvents, the membrane tegrated bipolar membranes enables to
voltage drop will be unacceptably high. split up salts into their corresponding acids
Possibly, in such cases a membrane can be and bases.
used in combination with a solvent on the
other side that enables a good conductivity
(e.g. an aqueous electrolyte). 2.5
The properties of the polymer backbone Electrochemical Cells
in an ion-exchange membrane determine
its stability against solvents and chem- The electrochemical cell is the apparatus,
ically aggressive conditions. The most which is finally needed to realize the
used polymer is polystyrene, crosslinked desired electroorganic conversion, and,
with divinylbenzene. But also many other therefore, its design has to consider, as far
polymers and polymer composites are ap- as possible, all the aspects discussed in this
plied in order to achieve an increased chapter. Furthermore, an uncomplicated
stability. A cation-exchange membrane and inexpensive manufacturing and an
of nearly universal chemical stability is effective and easy handling of the cell will
Nafion (Du Pont), a perfluorinated sul- be important.
fonic acid ionomer (industrially used
e.g. for chlor-alkali electrolysis), but it 2.5.1
is expensive and its swelling in or- Requirements in Electrochemical Cells
ganic solvents is high. Anion-exchange
membranes are commonly less resistant The following items generally will be
than cation-exchange membranes, espe- essential, but their importance depends
cially at elevated temperatures and against on the individual reaction system and on
oxidizing and alkaline conditions. Most
the intention of the investigations such as
membranes include a woven fabric as
the following:
mechanical reinforcement. The optimal
membranes – cation- or anion-exchange • uniform current density (i.e. uniform
membranes – should be selected for the current distribution),
specified application from the large num- • uniform mixing and mass transfer,
ber of membrane types, using the technical • constant temperature,
advice of the suppliers. • construction materials, that do not
An additional interesting application of corrode.
ion-exchange membranes for the treat-
ment of electroorganic product solutions Successful handling of the cell and perfor-
is the ‘‘electrodialysis’’ (e.g. [70, 72]). It mance of the electrolysis requires:
2.5 Electrochemical Cells 55
• uncomplicated and leakproof mounting, upper part of the cell. Thus, the cell con-
• error-free sampling, struction has to enable a fast displacement
• exact mass and charge balancing. of gases from the electrolyte between the
electrodes or between the separator and the
Possible further requirements are as electrodes (see Sect. 2.4.1.2.2). The current
follows: density has to be limited so that the gases
• reliable potential measurement, can be discharged without problems.
• inert gas atmosphere,
• balancing of a gas evolution, 2.5.1.2 Uniform Mixing and Mass Transfer
• reflux condenser to avoid a loss of sol- The significance of mass transfer for the
vent (this can be important especially in electrode reactions, that are in principle
case of gas evolution, an additional low- heterogeneous, has been discussed in
temperature cold trap may be suitable). Sect. 2.3.2.1, especially important at low
reactant concentrations. Therefore, local
Additional qualifications may be necessary differences in the movement within the
for special intentions. electrolytes should be avoided and a
uniform mixing is desired. In a number
2.5.1.1 Uniform Current Density of cases, a gas evolution at the electrode
The decisive influence of the current den- may be sufficient. Frequently, especially
sity on the electrode reactions – including in cells for batch operation, a (magnetic)
their selectivity – has been discussed in stirrer can be used (see Fig. 8).
Sect. 2.3.2.1. Therefore, a uniform current In flow-through cells, a design for
density on the entire electrode area usually optimal fluid distribution may be suitable
is indispensable. Precondition is a suffi- (see Figs. 9 and 10a). A further enhanced
ciently constant overall cell resistance – of mixing is attained using a ‘‘turbulence
the electrodes, the electrolytes, and the cell promoter’’, for example, a coarse woven
separator – for every point of the electrode mesh of polymer wires (see e.g. in
area. This needs satisfactory conductivities Fig. 13). The permanent shift in direction
of the electrode materials and adequately during the flow within the plane of the
dimensioned, symmetrical current feed- mesh results in a strong agitation. By
ers. For a constant electrolyte resistance, this way, also electrolyte chambers of
the electrodes have to be mounted parallel. small thickness can be realized in flow-
This becomes more and more important through cells. As an example, typically,
• with increasing current density, the chambers between the membranes
• with decreasing electrolyte conductivity, of electrodialysis stacks are built up by
• with decreasing electrode distance (for spacers of such a mesh, ca. 0.5 to 2 mm
reduced cell voltage). thick, with integrated elastomer sealing
gaskets (the inlet and outlet channels are
Examples of cell constructions, which pro- formed by punched holes in the gaskets,
vide a uniform current density, will be see Fig. 11). The optimal mixing increases
shown in Sect. 2.5.2. A significant distur- the limiting current density and the minor
bance of the current density distribution distance prevents a too high voltage, so
can be produced by gas evolution, espe- that even very diluted solutions can be
cially in case of vertical electrodes in the electrolyzed. Gases may be problematical
for turbulence promoters as gas bubbles [J], T , absolute temperature [K], S,
can adhere to the mesh. reaction entropy [J K−1 ]) is converted into
heat and has to be dissipated from the
2.5.1.3 Temperature Control cell. Substantially, it is the consequence
The rate of electrochemical reactions is of the overvoltages (see Sect. 2.3.2.1), the
given by the cell current, that is, in princi- part that is caused by ohmic voltage drops
ple, it can be controlled independent of is the ‘‘Joule heat’’. Small cells usually
the temperature (the required overvolt- need a heating for applications at elevated
ages are influenced by the temperature, temperature, but for larger cells and high
however). But usually, electroorganic con- cell currents a sufficient heat dissipation
versions include chemical reaction steps is required.
and therefore the temperature influence, The easiest temperature controlling
especially on reaction kinetics and selec- method for small cells is a jacket round
tivity, is frequently similar to that of pure the cell that is connected to the fluid cir-
chemical reactions. Consequently, a con- culation of a thermostat (see Fig. 8). For
stant temperature is desirable to achieve flow-through cells, especially when they
clearly defined conditions for the investi- are running in batch operation with cir-
gations. culation through a reactant reservoir, a
Typical for electrochemical systems is heat exchanger (e.g. of glass) should be in-
the increasing conductivity of electrolytes cluded into the cell liquid loop. Probably,
and the reduced cell voltage with increas- the backsides of the electrodes can be used
ing temperature. Therefore, an elevated as heat-exchanger area for temperature
temperature may be suitable, as high as the controlling (caution: without additional
chemistry of the reaction system allows. protection, e.g. by insulating, it is not
An additional limit is the boiling tem- allowed to bring the backsides of both elec-
perature of the electrolyte. Vapor bubbles trodes in contact with a noninsulating tem-
will increase the resistance and the voltage perature bath fluid (e.g. water), because
drop of the electrolyte so that additional the potential difference will initiate severe
heat will be evolved and the temperature damages by (pitting) corrosion, probably
will further increase, that is, an instable even in the thermostat, that is electrically
situation will occur. Such effects especially connected to earth). More sophisticated
may be expected at locations of lower con- temperature controlling methods, for ex-
ductivity, for example, in a diaphragm. Any ample, using temperature sensors in the
local overheating (‘‘hot spot’’) will cause a cell, electronic controllers and electrical
loss of yield and selectivity and probably quartz heaters, are practically proven.
a damage of cell components. Therefore,
this has to be prevented by temperature 2.5.1.4 Construction Materials
controlling in combination with the mix- Glass will be the most applied material
ing of the electrolytes and by choosing for small cells (see e.g. Fig. 8). It is
suitable operation conditions. insulating and resistant against most
The consumed electrical energy is U · I electrolytes, except strongly alkaline and
(U , cell voltage [V], I , cell current [A]). The fluoride-containing media, and it can
part U · I − H , that exceeds the enthalpy be used up to high temperatures. An
of the cell reaction H = G + T · S important advantage is the possibility to
(G, reaction free enthalpy (Gibbs energy) observe reactions directly, for example,
gas evolution, color changes, formation in thin layers such as films or tube
of two phases, or precipitation of solids. walls. Especially PTFE, which cannot
Complex constructions can be realized by be molten but only sintered, is always
a glassblower. Coupling devices such as porous. If this is a problem, fusible but
ground-glass equipment, flanged joints, more expensive fluorinated polymers can
and screw cap connections for easy be used, such as perfluoroalkylvinylether
handling are available in a large variety and (PFA) or fluorinated ethylene-propylene
different diameters. Glass is completely (FEP). A thin FEP film, for example,
tight, any diffusion into and out off the is useful for insulating and shielding of
cell is impossible (e.g. of oxygen or solvent metal surfaces.
vapor). If necessary, for example, in case Materials for gaskets have to be chemi-
of extremely oxygen-sensitive compounds, cally stable and should be elastic in order
the glassblower can substitute coupling to reduce the required force for sealing.
devices by direct connections. But the Frequently, O-rings, that need a groove for
problem of glass, particularly for enlarged fixing, or flat gaskets, which can be cut
cells, is its breakability. from sheet material, are applied. Unfortu-
Mechanically robust materials are met- nately, common elastomers, also for exam-
als, for example, different chromium- ple, silicon rubber or ethylene-propylene-
nickel steels, or titanium. Their use in diene copolymer (EPDM), are attacked
electrochemical cells is limited because by many organic solvents (swelling) and
they are conductive and may corrode. have to be tested for each case in de-
The corrosion is significantly influenced tail. Fluorinated elastomers, for example,
when the metal is insulated or connected ‘‘Viton ’’ or ‘‘Kalrez ’’, may be suit-
to the anode or to the cathode (see able but are expensive. Probably, O-rings
Fig. 9). with an elastic silicon rubber core and
Polymers, for example, polypropylene a resistant FEP jacket can be help-
or polymethylmethacrylate (PMMA, ful. A paste of pure PTFE is available
‘‘Plexiglas ’’ transparent) and many that can be used like joint grease for
others, may be interesting materials of easy sealing.
machinability. But their chemical stability, An all-purpose gasket material is ex-
especially against organic solvents, has to panded PTFE (‘‘Gore-Tex ’’ and similar
be tested individually. products, but expensive and only usable
Chemically universally stabile is poly- once). It is available as a cord of various
tetrafluoroethylene (PTFE, ‘‘Teflon ’’), but diameters ≥1 mm or as sheet material.
it is relatively expensive. A problem is the Initially, it is very soft and can be adapted
‘‘cold flow’’, that is, the polymer is slowly to each surface (it is, for example, even
deformed under the mechanical stress of possible to mount a metal mesh elec-
the pressure on the gaskets and a leakage trode tightly between glass flanges and
of the cell can occur (PTFE compounds, to connect the edges outside with a cur-
e.g. with glass powder or graphite, show a rent feeder). The cord will be formed to a
better behavior.) closed loop by inclined cutting and over-
It has to be considered that lapping. It can be fixed for mounting by an
polymers – different from glass and integrated adhesive stripe or by the above-
metals – generally are more or less mentioned PTFE paste. During mounting,
permeable for gases and vapors, mainly the gasket will be strongly compacted.
With a small pressing force, a leakproof Various fluoropolymer equipment, for

sealing for aqueous solutions is possible. example, connectors and valves, is avail-
To become tight against gases and vapors, able from laboratory suppliers (at a high
an increased force is required (by strong price). The principle of a simple, quick,
pressing, up to a translucent appearance, and inexpensive method for connections
even applicable for high-pressure cells). of electrochemical cells using PTFE tubes
No could flow as in case of common PTFE is shown in Fig. 4.
occurs. If vulnerable materials, such as a A PTFE tube (1), for example, with an
membrane or mesh, have to be mounted, outer diameter of 3 mm and an inner
a preforming of the gaskets is suitable, diameter of 2 mm, is cut some centime-
that is, preliminary mounting of the cell at ters longer than finally needed. Tubes
reduced force with a plastic film instead of from 0.5 mm up to 6 mm outer diame-
these sensitive materials. ter have been successfully applied with
Generally, a constant, sufficiently strong this method. The tube is heated at the
pressure on the gaskets is necessary, but end (ca. 2–3 cm) with a hot air blower
it must not be too high so that, for until it becomes clearly transparent (2,
example, gaskets or membranes, and cell ca. 250 ◦ C, using a gas flame includes
parts, for example, of glass or PTFE, the risk of overheating and decomposi-
could be damaged. Therefore, an elastic tion of the polymer). Then the tube is
construction is suitable. This function may quickly stretched so that the diameter be-
be performed by the gaskets themselves, comes smaller than the borehole (3). The
if they are sufficiently thick and elastic. squeezed end is cut off (4).
Probably, a (silicon) rubber sheet of A capillary of glass or another material,
some millimeters thickness can be added for example, PTFE or metal, is cut to about
between the first cell part and the fixing 2 cm (5). It can be part of a larger device
plate. Also, cup springs as washers at the too. The method can also use any other
screwing of the cell are practically proven. cylindrical borehole of sufficient length
1 PTFE tube
2 Heating
3
Elongate
4 Cut off
5 Removing
of any burr
Capillary and sharp
(e.g. of glass) edge
6 Fig. 4 Leakproof fixing of PTFE tube in

a borehole, here in a glass capillary, that
7
can be linked to a common screw cap
8 connection (borehole diameter about
Cut off 20% lesser than the original outer
9 Heating diameter of the tube, length of the
borehole at least three times
10 Cut off the diameter).
(at least about three times the diameter) (otherwise, a loss of vaporized liquids is
in any material, for example, polymers, difficultly observable).
metals, or also glass. For the chosen tube • Partial balances of all compounds, that
of this example, the diameter should be is, the individual reactants have to
2.4 mm. Any burr or sharp edge has to be be found in the products, considering
removed (see enlarged picture (5); in case stoichiometry.
of the glass capillary this is possible using This will be helpful to detect the reason
a file or hard-metal tool or by melting). if there is a loss of single compounds.
The elongated end of the tube is drawn • Charge (current) balance and calculation
through the capillary (6) and fixed in a of the current efficiency (see Sect. 2.3.1),
vice. Then the capillary – or the device with that is, the electrochemical products
the borehole – is moved on the tube to the
on both electrodes, including product
desired position (7). A considerably strong
gases, have to be equivalent to the
and constant force during this movement
consumed electrical charge.
shows that a leakproof connection between
This can also detect a partial elec-
the tube and the capillary can be expected.
trical shortcut or, more probable, an
Again the squeezed end is cut off (8).
The part of the tube, that has been ‘‘electrochemical shortcut’’, that is, the
drawn through the capillary, will be consumption of a product of an elec-
largely elongated. Its original length and trode at the other one, for example,
diameter can be reestablished by heating anodic oxidation of hydrogen, that has
to clear transparency (9, a heating of been evolved at the cathode.
the capillary itself should be avoided). The effort to carry out all these balances
If the tube is then cut off at about is high, but it significantly increases the
2 mm (10), this is a protection against
reliability of the results, that should be
pulling out. For building up a further
based not only on single measurements
connection, the process can be repeated
(analyses). Usually, incorrect data are only
with the reestablished PTFE tube. The
detectable on the basis of at least two
practicability of this method has been
independent values or balances. If vari-
proven even in a pressure electrolysis cell
at 5 bar. ous balances are found, often an error
can be identified as a false measurement
or analysis mistake and not a real fail-
2.5.1.5 Mass and Charge Balancing
ure. As far as possible, several samples
At a first glance, it may be sufficient
should be taken during each experiment
to detect the desired product but a
for improved reliability. For continuous
comprehensive information about the
operation under stationary conditions, the
investigated conversion needs mass and
average of some measurements and anal-
charge balancing.
yses will be used (any tendency in the
• Total mass balance, that is, the sum individual values shows that the stationary
of inputs has to be equal to the sum state is not yet achieved). In case of batch
of outputs. This will be particularly operation a consistent change with time
interesting for long term and generally confirms reasonable results (here, in the
for continuously operated investigations mass balance the decrease of the cell liquid
in order to detect a possible leakage by the sampling has to be considered).
An easy way for sampling of the cell fluid has proved its practicability [74] (caution:
is to mount a screw cap with a septum explosive gas mixtures can be formed in
at a suitable place of the cell (the cell electrochemical cells; an antisplinter pro-
fluid should not permanently be in contact tection has to be provided!). The fluid
with the septum and a loss out of the has to be selected for minimal solubil-
gas-phase through the perforated septum ity of the gas, for example, for carbon
should be avoided). The cheap common dioxide containing gases an acidified, sat-
medical disposable syringes, which are urated salt solution. Solvent vapors must
available in various types with needles of be condensed previously. Addition of a de-
different diameter and length, can be used. tergent facilitates a uniform overflow at
The coupling of the cell with a syringe is the fluid outlet. The valves may be simple
also possible using PTFE tubes according hose cocks. The level of the fluid outlet
to Fig. 4 (direct fixing in the connector of is adjusted so that the gas can stream
the syringe or via a capillary that includes in nearly without pressure (observable at
the conic adaptor for the syringe). the manometer).
As mentioned above in Sect. 2.4.1.2.2, The overflowing fluid is equivalent to the
frequently gases are evolved during elec- gas volume. If the measurement has to be
trochemical reactions, especially at the more exact than about 3%, corrections con-
counter electrode. Information about vol- cerning the actual atmospheric pressure,
ume and composition of one or both of the decreased pressure due to the height
these gases can be necessary to clarify the h of the fluid and the vapor pressure of
electrochemical process. Probably small the fluid are possible [74]. Additional er-
gas amounts have to be sampled. The gas rors can occur if the gas is significantly
sampling device in Fig. 5, made of glass, soluble in the fluid.
Gas
Flexible tube
Ov inlet
V5 Screw V4
cap
with Measuring
sample
volume
septum volume
Gas
Manometer
Flexible tube
V1
Thermo-
meter
V6
∆h Fig. 5 Gas sampling device
Filling with fluid: V1 and V2 are closed,
V4, V5, and V6 are opened, V3 is opened
until the device is filled completely and
Out- the fluid runs over at Ov;
let Fluid Operation: V3 and V4 are closed, V2 is
widely opened, when the overflow at the
Fluid fluid outlet is finished, V1 can be
outlet V3
opened for the gas;
V2 Gas transfer: like filling with fluid until
Fluid
the gas is transferred into the gas
inlet
sample volume.
The level of the overflow Ov should entire cell voltage – can indicate a variation
be elevated for transferring the gas into of the electrode reaction.
the sample volume for realizing a slight An exact potential measurement is
excess pressure. Then the sample volume, difficult – particularly in organic electro-
after closing of V5 and V6, can be carried chemistry – and probably requires very
away (probably with a residue of fluid) and sophisticated techniques to avoid a variety
samples for gas chromatography can be of possible errors (e.g. [75]). Fortunately,
taken through the septum with a gas-tight for practical applications in electroorganic
syringe, without the risk of contamination synthesis, it will usually be sufficient to
due to immigration of air. Nevertheless, get reproducible potentials for the cur-
the samples should be analyzed as soon rent density–potential curves (see Fig. 1)
as possible because a diffusion of air into as well as for the synthesis cell. A constant
the sample volume is practically inevitable deviation in both measurements may be
(shown by the presence of nitrogen in acceptable, even though the accurate value
the analysis). may be unknown. Some aspects will be
Generally, a continuous recording of discussed here, a more detailed overview
electrically available data – for example, is given, for example, in [3a].
current, cell voltage, electrode potentials,
temperatures – is beneficial to supervise 2.5.1.6.1 Reference Electrodes By defini-
the proper procedure of each experiment. tion, the normal hydrogen electrode (NHE)
Especially in case of a failure this will is the reference for electrode potentials (see
be a valuable help to find the reason. Sect. 2.3.2.1), but practically it is scarcely
Today, the best way is to use a data usable. A reference electrode (RE) has to
acquisition system in a computer that provide a well-defined potential between
offers the results directly for further the electrolyte and its electric connector,
calculations, for example, integration of joined with the input of the measuring in-
the consumed current (converted charge). strument. Usually, a metal and a slightly
For continuously operated experiments soluble salt of this metal is applied (sec-
the addition of scales, which acquire the ondary electrode) [76, 77]. The electrolyte
weight of input and output reservoirs, will in the RE is connected to the electrolyte in
be advantageous in order to supervise the the electrochemical cell via a diaphragm,
mass balances continuously. which has to separate both electrolytes, as
far as possible without a potential differ-
ence (see below).
2.5.1.6 Electrode Potential Measurement A classical system is the saturated
The central importance of the electrode calomel electrode, SCE (Hg/Hg2 Cl2 /satu-
potential has been discussed in Sect. 2.3.2. rated KCl in H2 O) with a potential of E =
The potentiostatic operation mode evi- +242 mV versus NHE (25 ◦ C). The disad-
dently requires a reliable potential mea- vantage is the sensitivity against a current
surement. Only experiments at constant flow through the system (generally, poten-
current can operate without knowledge of tials should be measured only using instru-
the potential. But here too the potential of ments with a very high input resistance,
the working electrode imparts interesting that is, nearly currentless with maximally
information, for example, a change in this 1 nA). The systems [Hg/Hg2 SO4 /sat.
potential – probably not detectable in the K2 SO4 in H2 O] E = +650 mV versus
NHE (25 ◦ C) or [Hg/HgO/1n NaOH in of the separator and on the flow rate of
H2 O] E = +140 mV versus NHE (25 ◦ C) KCl solution through the separator. Usual
are, for example, interesting if chloride separators are sintered glass or ceramic di-
ions are not allowed. A problem of all mer- aphragms or, for example, a plug of agar.
cury containing systems is the toxicity. A In practical applications, mostly a contam-
nontoxic system is [Ag/AgCl/sat. KCl in ination of the cell electrolyte with chloride
H2 O] E = +197 mV versus NHE (25 ◦ C). ions is undesired (probably formation of
It is nearly temperature independent and chlorine at the anode). But, a poorly perme-
insensitive against current flow. It can be able separator can produce high potential
easily prepared by anodic oxidation of a differences. An alternative is the change to
silver wire in KCl solution (coating with an the inert K2 SO4 solution. In contact with
AgCl layer, subsequently an excess of solid an organic electrolyte, indefinable condi-
KCl is added to the electrolyte round the tions with significant potential differences
silver wire). But, diffusion of silver ions are possible. Also, a transfer of water may
out of the partially soluble AgCl can be be detrimental in this case. As mentioned
a problem. above, an RE system, that is compatible
The potential of the RE may be changed with the cell electrolyte, should be used,
by infiltration from the cell electrolyte. even though the potential could be prob-
Thus, the combination of cell electrolyte lematically to define.
and RE has to be carefully selected [3a, 76, All these possible difficulties show that
77]. Probably, a reference system in the an accurate potential measurement is
same solvent as in the cell will be suitable, mainly possible in uncomplicated aque-
for example, Ag/0.01 m AgNO3 /0.1 m ous solutions. In electrolytes, for elec-
NaClO4 in acetonitrile, E ≈ +500 mV troorganic syntheses, especially in aprotic
versus NHE (25 ◦ C) [78]. solutions, significant deviations are to be
expected. But, as mentioned above, this is
2.5.1.6.2 Diffusion Potentials At the no problem for practical applications if it
interface between two different solu- can be verified that the acquired potential
tions – here, between the electrolyte of values are reproducible.
the reference system and the cell elec-
trolyte – significant potential differences 2.5.1.6.3 Luggin Capillaries The loca-
can occur. The ‘‘diffusion potential’’ is tion, where the potential of the electrolyte
caused by a different diffusion velocity should be measured, is connected to the
of cations and anions, as it is evident RE by the Luggin (Haber–Luggin) capil-
for acids and bases due to the extraor- lary. Its design can significantly influence
dinary high mobility of H+ and OH− the accuracy of the acquired potential val-
ions. In strongly acidic or alkaline aque- ues. Requirements are
ous electrolytes, several ten millivolts may • optimal position in front of the
be obtained. This can be reduced using electrode,
a ‘‘salt bridge’’ with a high concentrated • sufficiently low resistance,
electrolyte, whose cations and anions have • undisturbed operation.
the same mobility, for example, potassium
chloride (KCl is often contained in RE Different positions of the Luggin capil-
systems). Additionally, the potential dif- lary are shown in Fig. 6 [4]. In example 1,
ference may be dependent on the type a too large distance between the working
Fig. 6 (From Ref. [4]) Positioning of the W

Luggin capillary. problematic: 1–3; C L I
I
suitable: 4–6; W: working electrode; L:
Luggin capillary; C: counter electrode; I:
I •R
cell current, R: electrolyte resistance.
1 2 3
2d
2/3 d d
4 5 6
electrode and the tip of the capillary causes overvoltages are remaining at the sta-
a considerable voltage drop due to the re- tionary value. Comfortable potentiostats
sistance R of the electrolyte layer and the include automatic potential correction pos-
cell current I . This voltage drop increases sibilities (e.g. [79, 80]).
linearly with rising I and can overlay the An adequately high input resistance is
current density potential curve (see Fig. 1), ensured using a potentiostat (other in-
so that changes in the overvoltages, which struments probably need an additional
are important for the electrode reactions, amplifier like for pH electrodes). Neverthe-
may not be detectable. In example 2, there less, the resistance of the Luggin capillary
is no distance so that at the location of has to be sufficiently low. This is unprob-
the capillary tip the current is interrupted lematic using the classical glass capillary,
and the measured potential is incorrect. A filled with high concentrated KCl solution
recommended position is shown in exam- (see part 10 of Fig. 8b, combined with a
ple 5: the distance is equal to the twofold container for the RE). For reducing the
outer diameter d (d ≈ 1 mm, inner diam- effective resistance – especially, if a longer
eter 2/3 d). It is difficult to fix this position; capillary is needed and/or if electrolytes of
thus, the tip of the capillary is turned up in lower conductivity have to be used in the
example 4, and the edge can be placed di- capillary – a thin wire of a noncorroding
rectly on the electrode. No disturbance is to metal (e.g. platinum) can be inserted into
be expected in example 6, but this design the capillary (no contact to the electrode!).
is not realizable everywhere. The position Additionally, it will be favorable to guide
behind the electrode in example 3 is some- the wire outside the capillary and to con-
times reported in the literature, but the nect it via a high insulating capacitor par-
uneven current density distribution may allel to the RE with the input of the poten-
initiate deviations. tiostat (no influence on the stationary po-
The voltage drop I · R should be esti- tential value, but stabilization of the poten-
mated and eliminated from the measured tiostat in the higher frequency range [81]).
potential. It can be directly determined by Penetration of gas bubbles into the
fast current interruption measurements: Luggin capillary can disturb the steady
about 1 µs after shutting down the cur- operation. In the worst case, the control
rent, the potential is already decreased by circuit of the potentiostat will be inter-
all ohmic voltage drops while all other rupted and the cell current can increase
uncontrollably up to the positive or neg- allows to easily modify the design for spe-
ative maximum value (a damage of cell cial requirements. The following examples
components can be possible). The turned are presented to give some ideas for own
up tip of the capillary in example 4 of constructions. The chosen industrial cell
Fig. 6 is a possibility to avoid this. Also, designs include a commercial cell that is
the platinum wire within the capillary, available also on a small scale and therefore
mentioned above, increases the security can be used in the laboratory.
against perturbation by gas bubbles. Even
a PTFE tube, otherwise extremely sensi-
2.5.2.1 ‘‘H-cell’’
tive to blocking by gas bubbles due to its
The classical H-cell (Fig. 7, with a shape
hydrophobic properties, can be used as a
Luggin capillary with a platinum wire in- similar to the letter ‘‘H’’) is, for exam-
side (easy mounting through the cell wall ple, suitable for demonstration of simple
like in Fig. 4). electrochemical experiments, such as wa-
ter electrolysis. In the vertical containers,
2.5.2 the electrodes can easily be mounted; the
Examples of Electrochemical Cells horizontal connection between anode and
cathode compartment is divided by a di-
The equipment for electroanalytical meth- aphragm. This cell can have a large energy
ods usually includes the required cells, loss due to a high cell voltage, and the
but standardized preparative scale electro- current density at the electrodes is very
chemical cells are scarcely available (some unevenly distributed. As discussed above,
equipment is offered, for example, by the these problems may be disadvantageous
Electrosynthesis Company Inc., Lancaster, for electroorganic conversions in this cell
USA). Most of the electrochemical cells, type. Nevertheless, there are many ex-
used for the investigations in the liter- amples of the successful application of
ature, are made in the facilities of the similar cells, also using a mercury cathode
institutes, especially by glassblowers. This (e.g. [82, 83]).
+ −
Fig. 7 H-cell.
A comparable cell design – but with flat, heating or cooling is connected to a ther-
solid, or perforated electrodes, mounted mostat. Similarly, in an undivided cell,
parallel nearby the diaphragm – avoids the vertical, parallel, or concentric electrodes
above-mentioned problems and can work can be used.
with optimal current distribution [84].
2.5.2.3 Flow-through Cells
2.5.2.2 Beaker Glass Cells Flow-through cells enable optimal flow
For investigations in batch operation, us- conditions. They can work in continuous
ing a small reactant volume, a beaker glass operation at stationary conditions as well
cell like the one in Fig. 8 is optimal [85]. as in batch operation if they are coupled by
The reaction is directly observable. In the a circular flow to a reactant reservoir (see
example, a mercury cathode and a plat- Sect. 2.3.4).
inum mesh anode (with a platinum wire In Fig. 9, the cathode block (4) of stain-
ring as current feeder) are used. A mag- less steel includes inlet and outlet channels
netic stirrer provides the mixing of the (6) that are each connected by 6 boreholes
electrolyte and renewal of the mercury for uniform flow distribution to the cath-
surface. The parallel mounting of the elec- ode surface (details see cross section 7).
trodes enables a uniform current density. The anode (2) is a platinum foil of 18 cm2
If the cell has to be divided (Fig. 8b), the active area with the brass cover plate (1) as
anode is enclosed in a glass tube with a current feeder. The electrode distance is
diaphragm. An RE with an integrated Lug- given by the sealing gasket (3), for example,
gin capillary can be added. A jacket for silicon rubber of 0.2–1 mm [85].
+ −
10 + 4
12 9
4 2 − 2
11
8 8 11
13 13
4
12 3
5
4 10 6
3
2 7 2
7 1 1
13 13
(a) (b)
Fig. 8 Beaker glass cells (a) undivided, (b) divided. 1 mercury
cathode, 2 cathode current feeder, 3 platinum mesh anode, 4 anode
current feeder, 5 anolyte tube with, 6 diaphragm, 7 magnetic stirrer,
8,9 PTFE stopper, 10 reference electrode with Luggin capillary,
11 reflux condenser, 12 thermometer, 13 connection to thermostat.
A similar design with a second block dimensions, thickness, and required con-
as anode, for example, of coated titanium nections of the cell compartments. The
or graphite, can be used as divided cell desired electrodes, diaphragms, and/or
with a flexible diaphragm or an ion- ion-exchange membranes and the nec-
exchange membrane. essary cell chambers between – also for
If both electrodes have to be made of example, gas supplying chambers for
materials, that are available only as foils GDEs or heating/cooling chambers – can
or sheets or are not machinable, or for simply be combined and mounted by fix-
example, for materials, such as graphite ing plates and screws. Electrode plates or
felt, a cell design like the one in Fig. 9 foils – even of large dimensions – can be
is not realizable. Inlet and outlet systems applied without any machining like the
have to be integrated in the electrolyte cathode in Fig. 10b, using the edges as
compartments. The ‘‘parallel-plate and current feeders (electrode distance from
frame’’ design of a laboratory flow-trough the membrane = frame + sealing gas-
cell in Fig. 10 consists of easy-to-produce kets thickness). If a reduced electrode
parts, using the fixing method for PTFE distance for low cell voltages is needed,
tubes in Fig. 4. a perforated electrode of a suitable ma-
The rectangular frame in Fig. 10a en- terial can be connected in an adequate
ables a similar mixing quality in the cell distance in front of a current feeder
chamber as in the cell of Fig. 9 (for re- plate (‘‘preelectrode’’), like the anode in
duced mixing requirements less tubes are Fig. 10b.
sufficient). Ring-shaped frames as shown The cell design in Fig. 10 can be applied
in Fig. 10b can be particularly easy ma- without flow-through in batch operation
chined by turning, or simply can be cut too, for example, for easy testing of
from thick-walled tubes, including glass. electrode or separator materials. Then, the
A cell design like the one in Fig. 10 is frame thickness is chosen for the desired
very flexible concerning material, shape, cell compartment volume (for a thickness
+
1
6
4
5 − 7
Fig. 9 Example of a laboratory
flow-through cell.
+ −
A G G M G G C
AC CC
(a) (b)
Fig. 10 Examples of parallel-plate and frame designs for laboratory
flow-through cells (a) cell chamber for strong mixing and (b) various
parts of a cylindrical cell. A: anode (with preelectrode); G: sealing
gaskets; AC: anode compartment (glass ring, reduced mixing
requirements); M: membrane (diaphragm); CC: cathode compartment
(three tubes for gas outlet, sufficient mixing by gas evolution); C:
cathode (current feeders outside the cell at the four corners).
above ca. 15 mm, also a magnetic stirrer frame design (‘‘filter press cell’’, in prin-
can be used). ciple comparable to Fig. 10b). All compo-
nents – electrodes (plates), fluid distribu-
tors (frames), membranes or diaphragms,
2.5.2.4 Industrial Scale Cells
and sealing gaskets – have punched holes
at the same position so that different chan-
2.5.2.4.1 Parallel-plate and Frame Cells (Fil-
nels are formed through the entire stack
ter Press Cells) The design of industrial
cells has to combine many cell units in a (here eight channels). The fluid distrib-
cell stack with a sufficient electrode area. utors – for example, cathode and anode
The optimized supplying of reactants and compartments or electrodialysis cham-
the draining of products, probably includ- bers – are connected to the appropriate
ing gases and/or circulation streams, is channels by boreholes in the frames, for
a special challenge. Owing to the large example, the cathode compartments at
variety of requirements for electroorganic the bottom with the catholyte inlet chan-
syntheses, a modular system is needed nel and at the top with the catholyte
(‘‘building blocks’’). Figure 11 shows an outlet channel. Various fluid distribu-
example of a commercial cell that is avail- tors are possible (e.g. different thickness
able in different dimensions, including a and fluid distribution, probably turbu-
laboratory scale cell. lence promoters).
The exploded view in Fig. 11 elucidates Two electrical connection modes for the
the function of this parallel-plate and electrodes in a cell stack are possible:
Electrode
Fluid distributor
Membrane
(b)
(a)
Fig. 11 Examples of commercial cells (ElectroCell AB, Sweden) (a) Parallel-plate and frame
industrial scale cell (area of one electrode: 0.001 m2 (laboratory); 0.01 m2 (pilot plant);
0.04–0.4 m2 (production); up to 16 m2 in one cell stack). (b) Laboratory scale cell.
• ‘‘monopolar’’, all anodes and cathodes 2.5.2.4.2 Capillary Gap Cells The cap-
are connected in parallel to the current illary gap cell in Fig. 12 [4] is used in
feeders (see Fig. 11a); this requires high various industrial electroorganic synthe-
current at low voltage, ses, for example, [57, 63], including a
• ‘‘bipolar’’, the cell units are connected ‘‘paired electrosynthesis’’ for generating
in series, that is, cathode and anode useful products at both electrodes [86]
of adjacent cell units are combined, (BASF AG, Germany). The distances in
ideally one side of the electrode works as a stack of circular graphite plates (1) are
cathode and the other one as anode, the fixed to about 1 mm by plastic stripes,
current feeders are connected only to the forming the capillary gaps (2). The cell
electrodes at the ends of the cell stack; fluid is pumped into the central chan-
this requires high voltage at low current. nel (3) and streams radially outside where
it runs down and is recycled and cooled
Cell construction, current feeders and (4). The graphite plate at the top is
power supply are less expensive for the connected to the cathodic (6) and that
bipolar connection (see also Fig. 12), but at the bottom to the anodic current
the different potentials of all electrodes feeder (5).
can be problematical (e.g. shunt currents, In this undivided, bipolar cell, the top-
additional by-products, and corrosion in sides of all the graphite plates are work-
the channels). ing as anodes and the bottom sides as
Fig. 12 Capillary gap cell (From

+
Ref. [4]): 1 bipolar electrode plates, 5
2 capillary gap, 3 electrolyte channel,
4 heat exchanger, 5, 6 current feeders.
cathodes. The small electrode distance en-

6
ables the use of low conductive electrolytes. −
A concentric capillary gap cell (up to
800 cm2 active area) is described in [87]. 1
A modified cell design like the one
in Fig. 12 uses, instead of the rigid 2
graphite plates, graphite felt, which is
passed by the liquid, and instead of
3
the gaps, diaphragms or ion-exchange
membranes (solid polymer electrolyte
technology) [88, 51].
2.5.2.4.3 Swiss Roll Cell This cell has

been developed in Switzerland [89]. A 4
commercial application is one oxidation
step at a NiOOH anode in alkaline solution
for the vitamin C production [22]. Mesh Advantages of this cell design are
electrodes of stainless steel (cathode 1) and as follows:
nickel (anode 3) are rolled up together with
spacers of polypropylene mesh (2,4) on the • the small electrode distance enables
central current feeder (5) and mounted in a application of poorly conductive elec-
cylinder (cells up to 1 m diameter, 200 m2 trolytes;
active area). The electrolyte streams axially • the high electrode area per volume
through the cell. unit results in a high space-time
1 2 3 4
4
3
Fig. 13 Swiss roll cell. (From 2
Ref. [89].) 1
yield, even at very low current den- 7. H. Wendt, G. Kreysa, Electrochemical Engi-
sities; neering, Springer-Verlag, Berlin, 1999.
8. N.L. Weinberg, H.R. Weinberg, Chem. Rev.
• the high turbulence due to the mesh
1968, 68, 449–523.
structure (increased limiting current 9. Ch.K. Mann, K.K. Barnes, Electrochemical
density) allows an extensive reactant Reactions in Nonaqueous Systems, Marcel
depletion (high conversion). Dekker, New York, 1970.
10. A.M. Couper, D. Pletcher, F.C. Walsh, Chem.
Rev. 1990, 90, 837–865.
2.5.2.4.4 Innovative Cell Constructions 11. A. Savall, Actual. Chim. 1998, 4–15.
There are a lot of further innovative 12. G.E. Svadkowskaja, S.A. Votkewitsch, Russ.
cell constructions in the literature that Chem. Rev. 1960, 29, 161–180.
may also be suitable for electroorganic 13. H.J. Schäfer, Top. Curr. Chem. 1990, 152,
91–151.
syntheses, from laboratory up to industrial
14. W.J. Koehl Jr., J. Am. Chem. Soc. 1964, 86,
scale. Examples are rotating electrodes, 4686–4690.
application of ultrasound, and packed or 15. X. de Hemptinne, J.C. Jungers, Z. Phys.
fluidized particle bed three-dimensional Chem. (Muenchen) 1958, 15, 137–148.
electrodes for increasing the active 16. M.M. Baizer, J. Electrochem. Soc. 1964, 111,
electrode area and enhancing the mass 215–222.
17. T. Nonaka, K. Sugino, J. Electrochem. Soc.
transfer. A short overview is given, for 1967, 114, 1255, 1256.
example, in [1, 2]. 18. US 3,332,970, Shell Oil Comp. (Inv. G.
Smith), 1964.
References 19. J.M. Leger, J. Appl. Electrochem. 2001, 31,
767–771.
20. J. McBreen, Mod. Aspects Electrochem. 1990,
1. H. Wendt, H. Vogt, G. Kreysa et al., Electro-
chemistry, Ullmann’s Encyclopedia of Industrial 21, 29–63.
Chemistry, 6th ed., Wiley-VCH, Weinheim, 21. H.J. Schäfer, Top. Curr. Chem. 1987, 142,
2003 (Electronic Release 2001), Vol. 11, 101–129.
pp. 425–542. 22. P.M. Robertson, P. Berg, H. Reimann,
2. T.F. Fuller, J. Newman, M.P. Grotheer, K. Schleich, P. Seiler, J. Electrochem. Soc.
C.J.H. King, Electrochemical processing, Kirk- 1983, 130, 591–596.
Othmer Encyclopedia of Chemical Technology, 23. S. Rausch, H. Wendt, J. Electrochem. Soc.
4th ed., Wiley-Interscience, New York, 1994, 1996, 143, 2852–2862.
Vol. 9, pp. 111–197. 24. A. Martel, B. Mahdavi, J. Lessard, L. Bro-
3. H. Lund, O. Hammerich, (Eds.), Organic ssard, H. Menard, Can. J. Chem. 1997, 75,
Electrochemistry, 4th ed., Marcel Dekker, 1862–1867.
New York, 2001; (a) H. Lund, Practical 25. S. Donnelly, J. Grimshaw, J. Trocha-
problems in electrolysis, pp. 223–292; Grimshaw, Electrochim. Acta 1996, 41,
(b) H. Pütter, Industrial electroorganic 489–492.
chemistry, pp. 1259–1307. 26. S.R. Ellis, N.A. Hampson, M.C. Ball,
4. F. Beck, Elektroorganische Chemie, Wiley- F. Wilkinson, J. Appl. Electrochem. 1986, 16,
VCH, Weinheim, 1974. 159–167.
5. N.L. Weinberg (Ed.), Technique of Electroor- 27. H. Herbst, K. Petz, J. Stenzel, DECHEMA
ganic Synthesis, in Techniques of Chemistry, Monogr. 1992, 125, 243–257.
John Wiley & Sons, New York, Vol. 5; (a) Part 28. US 2,945,791 (Inv. F. D. Gibson Jr.), 1958.
I, 1974, (b) Part II, 1975; (c) Part III, Scale Up 29. R.H. Newnham, J. Appl. Electrochem. 1992,
and Engineering Aspects (Eds.: N.L. Weinberg, 22, 116–124.
B.V. Tilak), 1982. 30. J.-L. Caillerie, L. Albert, J. Power Sources
6. F. Goodridge, K. Scott, Electrochemical Pro- 1997, 67, 279–281.
cess Engineering, Plenum Press, New York, 31. N.L. Weinberg, Proc. Electrochem. Soc. 1984,
1995. 84-5 (Electrochem. Carbon), 463–478.
32. J.E. Graves, D. Pletcher, R.L. Clarke, F.C. 52. Y. Shen, M. Atobe, W. Li, T. Nonaka, Elec-
Walsh, J. Appl. Electrochem. 1991, 21, trochim. Acta 2003, 48, 1041–1046.
848–857; (b) 1992, 22, 200–203. 53. J.-Y. Nedelec, J. Perichon, Trends Org. Chem.
33. E.E. Farndon, D. Pletcher, A. Saraby Reint- 1992, 3, 173–178.
jes, Electrochim. Acta 1997, 42, 1269–1279. 54. J. Chaussard, M. Troupel, Y. Robin, G. Jacob,
34. E.E. Farndon, D. Pletcher, Electrochim. Acta J.P. Juhasz, J. Appl. Electrochem. 1989, 19,
1997, 42, 1281–1285. 345–348.
35. D. Bergner, S. Kotowski, J. Appl. Electrochem. 55. Q. Do, D. Elothmani, J. Simonet, G. Le Guil-
1983, 13, 341–350. lanton, Bull. Soc. Chim. Fr. 1996, 133,
36. E. Lodowicks, F. Beck, J. Appl. Electrochem. 273–281.
1998, 28, 873–880. 56. G.J. Janz, R.P.T. Tomkins, Nonaqueous Elec-
37. S. Trasatti, Electrochim. Acta 2000, 45, trolytes Handbook, Academic Press, New
2377–2385. York, 1972, Vol. I, II.
38. GB 1,195,871 (DE 1671422 C2, US 57. D. Degner in Ref. [5c] pp. 273–276.
3,632,498), Chemnor AG (Inv. H. B. Beer), 58. D.E. Danley, Hydrocarbon Process. 1981,
1967. 60(4), 161–164.
39. G. Foti, D. Gandini, C. Comninellis, Curr. 59. J.F. Rusling, Pure Appl. Chem., 2001, 73,
Top. Electrochem. 1997, 5, 71–91. 1895–1905.
40. C. Ravichandran, D. Vasudevan, S. Tanga- 60. L. Eberson, B. Helgee, Acta Chem. Scand.,
velu, P.N. Anantharaman, J. Appl. Ser. B 1978, B32, 157–161.
Electrochem. (a) 1992, 22, 1087–1090; 61. D. Pletcher in Electroorganic Synthesis
(b) 1992, 22, 1192–1196. [Manuel M. Baizer Meml. Symp.] (Eds.:
41. M. Fryda, L. Schäfer, I. Tröster, Recent Res. R.D. Little, N.L. Weinberg), Marcel Dekker,
Dev. Electrochem. 2001, 4, 85–97.
New York, 1991, pp. 255–262.
42. Y.V. Pleskov, Russ. J. Electrochem. 2002, 38,
62. J.D. Wadhavan, F.J. Del Campo, R.G.
1275–1291.
Compton, J.S. Foord, F. Marken, S.D. Bull,
43. M. Panizza, P.A. Michaud, J. Iniesta,
S.G. Davies, D.J. Walton, S. Ryley, J. Elec-
C. Comninellis, G. Cerisola, Ann. Chim.
troanal. Chem. 2001, 507, 135–143.
(Rome) 2002, 92, 995–1006.
63. D. Degner, Top. Curr. Chem. 1988, 148, 1–95.
44. R. Bellagamba, P.A. Michaud, C. Comninel-
64. J.O. Besenhard, (Ed.), Handbook of Battery
lis, N. Vatistas, Electrochem. Commun. 2002,
4, 171–176. Materials, Wiley-VCH, Weinheim, 1998.
45. G. Kreysa, Electrochim. Acta 1978, 23, 65. D.W. Rooney, K.R. Seddon in Ionic
1351–1359. liquids in Handbook of Solvents (Ed.:
46. M. Schleiff, W. Thiele, H. Matschiner, Chem. G. Wypych), ChemTec Publishing, Toronto,
Tech. (Leipzig) 1982, 34, 18–22. 2001, pp. 1459–1484.
47. K. Kordesch, G. Simader, Fuel Cells, Wiley- 66. F.G. Drakesmith, Top. Curr. Chem. 1997,
VCH, Weinheim, 1996. 193, 197–242.
48. E. Exposito, J. Gonzalez-Garcia, V. Garcia- 67. Z. Ogumi, K. Nishio, S. Yoshizawa, Elec-
Garcia, V. Montiel, A. Aldaz, J. Electrochem. trochim. Acta 1981, 26, 1779–1782.
Soc. 2001, 148, D24–D28. 68. J. Jörissen, Electrochim. Acta 1996, 41,
49. J. Wiesner, C. Christ, W. Führer et al., Pro- 553–562.
duction-integrated environmental protection, 69. K. Nyberg, M. Malmberg, R. Servin, AIChE
Ullmann’s Encyclopedia of Industrial Chem- Symp. Ser. 1979, 75(185), 36, 37.
istry, 6th ed., Wiley-VCH, Weinheim, 70. T.A. Davis, V. Grebenyuk, O. Grebenyuk in
2003 (Electronic Release 2001), Vol. 30, Electromembrane Processes in Membrane Tech-
pp. 89–192. nology in the Chemical Industry (Eds.:
50. N. Yamada, T. Yaguchi, H. Otsuka, S.P. Nunes, K.-V. Peinemann), Wiley-VCH,
M. Sudoh, J. Electrochem. Soc. 1999, 146, Weinheim, 2001.
2587–2591. 71. C. Gavach, C. Innocent, Actual. Chim. 1998,
51. E. Steckhan, T. Arns, W.R. Heineman, 28–36.
G. Hilt, D. Hoormann, J. Jörissen, L. Kröner, 72. R. Rautenbach, R. Albrecht, Membrane Pro-
B. Lewall, H. Pütter, Chemophere 2001, 43, cesses, John Wiley & Sons, New York, 1989.
63–73. 73. T. Xu, Desalination 2001, 140, 247–258.
74. J. Jörissen, Ph.D. Thesis, Universität Dort- 82. J.J. Lingane, C. Gardner Swain, M. Fields, J.
mund, Dortmund, 1982. Am. Chem. Soc. 1943, 65, 1348–1353.
75. A.J. Bard, L.R. Faulkner, Electrochemical 83. D. Peltier, M. Le Guyader, J. Tacussel, Bull.
Methods, 2nd ed., John Wiley & Sons, New Soc. Chim. Fr. 1963, (11), 2609, 2610.
York, 2001. 84. J.E. Dubois, A. Monvernay, P.C. Lacaze, Elec-
76. G. Milazzo, J. Electroanal. Chem. 1960, 1, trochim. Acta 1970, 15, 315–323.
265–284. 85. H.J. Schäfer, University of Münster, Ger-
77. D.J.G. Ives (Ed.), Reference Electrodes, 2nd ed., many; Personal communication.
Academic Press, New York, 1980. 86. H. Pütter, H. Hannebaum, Proc. Electrochem.
78. R.C. Larson, R.T. Iwamoto, R.N. Adams, Soc. 2000, 2000-15 (New Directions in Organic
Anal. Chim. Acta 1961, 25, 371–374. Electrochem.), 25–28.
79. D.K. Roe, Chapter 7 in Laboratory Tech- 87. L. Eberson, J. Hlavaty, L. Jonsson, K. Nyberg,
niques in Electroanalytical Chemistry (Eds.: R. Servin, H. Sternerup, L.G. Wistrand, Acta
P.T. Kissinger, W.R. Heineman), Marcel Chem. Scand., Ser. B 1979, B33, 113–115.
Dekker, New York, 1996, pp. 195–235. 88. US 6,077,414 (DE 19 533 773 A1), BASF AG
80. Manuals for potentiostats of different manu- (Inv. H. Pütter, H. Hannebaum), 2000.
facturers (search in the Internet). 89. P. Seiler, P.M. Robertson, Chimia 1982, 36,
81. Potentiostat Manual, Bank Elektronik – Inte- 305–312.
lligent Controls GmbH, Clausthal-Zellerfeld,
Germany.
73
3
Comparison of Chemical and
Electrochemical Methods in
Organic Synthesis
..
Hans J. Sch afer
.. ..
Organisch-Chemisches Institut der Universit at M unster, Correns-Str. 48149
..
M unster, FRG
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
3.2 General Aspects of Organic Synthesis . . . . . . . . . . . . . . . . . . . . . 75
3.3 The Reactive Intermediates in Organic Electrosynthesis . . . . . . . . . 76
3.4 Selection of Advantageous Electrochemical C,C-Bond Forming

Reactions and Functional Group Interconversions . . . . . . . . . . . . . 79
3.4.1 C,C-Bond Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
3.4.2 Functional Group Interconversions . . . . . . . . . . . . . . . . . . . . . . 81
3.5 Working Out An Electroorganic Synthesis . . . . . . . . . . . . . . . . . . 85
3.6 Equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
3.7 Some General Comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
75
3.1 This chapter is aimed at providing a

Introduction more realistic picture of the general scope
of electroorganic synthesis by giving a
When a chemist wants to synthesize an survey of favorable C,C-bond forming re-
organic compound he uses a familiar set actions and functional group interconver-
of equipment and methods. Familiarity sions (FGIs) at the electrode and pointing
and experimental skills are attained to a to the advantages of electrochemical meth-
large degree by his basic and advanced ods compared to purely chemical ones in
laboratory training and the methods he these cases. Furthermore, some hints on
used in his master’s and Ph.D. theses. the equipment used are given for begin-
Knowledge of reliable methods is devel- ners in the field. These points are dealt
oped at these instances by reading about with in more detail in other chapters of
and applying reactions from tested proce- this volume.
dures, for example, from organic synthesis
and literature reports on frequently ap-
plied reagents of good selectivity and
3.2
broad scope. Organic electrochemistry be- General Aspects of Organic Synthesis
longs to the category of less common
methods in a chemist’s experimental train-
ing. Consequently, the techniques and Organic synthesis is focused on the prepa-
reactions of this field tend to be used ration of a given target molecule [1–4].
only in special cases. Lack of experience Targets can arise from the structure proofs
and less developed experimental skills for new compounds, the generation of bi-
may lead to disappointment, which can ological activities or material properties,
cause a prejudice against the method. the support of a theoretical prediction, the
Often heard statements, which originate challenge to prepare a complex molecule,
mostly from hearsay rather than expe- or the extension of chemical methodol-
rience, are: the restricted scope of re- ogy. A good synthesis should fulfill a
actions, limited mechanistic knowledge, number of the following requirements:
necessity of special equipment, which it should involve few steps; provide a
is expensive and difficult to acquire, high selectivity; use cheap, readily avail-
long reaction times, and low yields and able, nontoxic reagents and solvents; al-
selectivities. low the recycling of expensive reagents;
76 3 Comparison of Chemical and Electrochemical Methods in Organic Synthesis
apply nonhazardous reaction conditions; carbocations and carbanions, or more

exhibit a good atom economy, that is, generally, electrophiles and nucleophiles.
it should transfer a maximum num- Radicals for chemical synthesis are gen-
ber of atoms of starting material and erated mostly by radical transfer reac-
reagents into the product, which also tions initiated by thermolysis or pho-
means a low production of waste; and tolysis of peroxides or azocompounds.
finally it should provide a broad scope This way a large variety of very se-
for converting readily available starting lective radical chain additions are avail-
materials into a large variety of pro- able [5].
duct structures.
Synthesis consists of (1) planning the re-
action sequence with respect to the given 3.3
conditions, (2) executing the optimal re- The Reactive Intermediates in Organic
action path, (3) isolating the product and Electrosynthesis
workup, and (4) improving yield and se-
lectivity of the conversion by changing In electroorganic synthesis, radical ions
reagents and reaction conditions. The preponderate as useful intermediates
difference between chemical and elec- (Scheme 1a). Radical cations can, in sub-
trochemical reactions lies mainly in the sequent deprotonations and further elec-
set of available reactions for points (1) tron transfers (ET), be transformed into
and (2) and the equipment used in carbocations or vice versa as radical an-
(2). These points will be addressed in ions can be converted by protonation
Sects. 3.4–3.6. and further reduction into carbanions.
Organic synthesis applies, in general, Carbanions can also be generated by re-
two types of reactions: C,C-bond form- ductive cleavage of R–X (X = Cl, Br,
ing reactions (C,C) for the construction I, OTos), and subsequent reduction of
of larger molecules from smaller units the intermediate radical R• (Scheme 1d).
and FGIs for the installation of the re- Radical anions can also be used as elec-
quired functionality (e.g. hydroxy, amino, trogenerated bases (EGBs, see Chapter 14)
keto, carboxyl, double bond) into the tar- for the deprotonation of C–H bonds to
get molecule or for the activation of the form carbanions.
synthetic subunits. The C,C-bond form- Electrogenerated radical ions nicely sup-
ing reactions can be classified as polar plement the methodology of chemical
reactions, in which an activated donor re- synthesis, whose reactions are less suited
acts selectively with an acceptor or vice to generate and use radical ions, but
versa; as radical reactions, which are in- rather apply polar substitution and addi-
creasingly applied in synthesis because tion reactions.
they do not interfere with polar groups Radicals are generated at the anode by
in the molecule [5]; and as pericyclic reoxidation of carbanions (Scheme 1b), for
actions, especially cycloadditions, for the example, alkoxides and carboxylates (see
construction of ring compounds with high Chapter 5, 6), and at the cathode by reduc-
stereoselectivity [6] and transition metal- tion of protonated carbonyl compounds or
catalyzed reactions [7]. onium salts (Scheme 1c) (see Chapter 7).
Polar reactions in chemical synthesis Thereby, a wide choice of different radi-
involve reactive intermediates such as cal structures can be mildly and simply
3.3 The Reactive Intermediates in Organic Electrosynthesis 77
Anodic oxidation Cathodic reduction
−H+ −e +e H+
(a) R+ RH+ • RH RH− • RH2−
−e +e
•
−e −H+
(b) R R− RH
H+ + +e •
(c) RX RXH RXH
+e −X−
(d) RX RX− • R−
+e
Scheme 1 Electrochemical generation of reactive intermediates for polar reactions.
obtained from readily available precursors. systems [4, 6]. After the Grignard reaction,
These radicals are especially suited for the Diels–Alder cycloaddition ranks sec-
coupling and additive-coupling reactions ond among the most applied methods
in nonchain processes because they are in organic synthesis. It plays a minor
favored by the high radical concentra- role in electrosynthesis; however, electro-
tions at the electrode. The electrogenerated chemically initiated cycloadditions have
radicals can be trapped by olefins to yield been described recently [8, 9]. They in-
additive dimers (1) (Scheme 2) and addi- volve chain reactions with a radical cation
tive monomers (3), or the adduct radical as the chain transferring step or the
can be further oxidized to a carbocation generation of reactive dienophiles (see
that reacts with a nucleophile to form (4). Chapter 5). Transition metal complexes
In additive dimers (1), two radicals and are powerful catalysts for C,C-bond form-
two olefins are joined in a one-pot reaction ing reactions. By way of in situ generation,
with a specific head-to-head connection of they are increasingly applied in electro-
the olefins. This is a unique structure pat- chemistry as electrocatalysts for cathodic
tern that is nearly exclusively available only coupling [10], reductive carboxylation [11],
by electrogenerated radicals. It is a conse- acylation or alkylation [12], activation [13],
quence of the high radical concentration in and cofactor regeneration in electroenzy-
the reaction layer at the electrode surface. matic reactions [14].
The product ratio (1) : (3) can in part be A synthetically very potent and unique
controlled by the current density and olefin feature of organic electrosynthesis is the
concentration (Scheme 2, paths a and b), oxidative or reductive ‘Umpolung’ of re-
and the formation of (4) by the electrode activity. Reactive acceptors are anodically
potential and the substituent of the olefin available as radical cations in a wide
(Scheme 2, path c) (see Chapter 5). variety by the oxidative ‘Umpolung’ of
Pericyclic reactions belong to the most donors. This way two donors can be
powerful methods for C,C-bond forming coupled in one step if one of them is
reactions, especially for the stereo- and re- converted to an acceptor at the elec-
gioselective construction of polycylic ring trode. Chemically, at least two additional
Y
a
R C C C C R
Y
(1)
Y Y Y
• b
R + C C R C C •
R C C R
R•
(2) (3)
Y
c
−e, Nu− R C C Nu
(4)
Scheme 2 Reactions of electrogenerated radicals.
steps are needed for this operation. Thus, to generate activated donors with differ-
electrochemistry saves steps in synthesis ent functional groups and carbon struc-
and allows the use of synthetic building tures by hydrogen–metal, halide–metal,
blocks in several reactivities, namely as or metal–metal exchanges. Furthermore,
donors, acceptors, and radicals. Of gen- in these cases, the low temperatures and
eral synthetic value is the generation of inert solvents, which are necessary to han-
latent immonium ions for electrophilic dle reactive and labile carbanions and to
addition (see Chapter 6) and the oxida- achieve high selectivities, can be applied.
tive coupling of olefins (see Chapter 5). For practical use, the lower temperature
In common chemical synthesis, there limit for preparative scale electrolysis is,
is, on the other hand, a highly devel- in general, at −50 ◦ C, because of the
oped experience and a large arsenal of decreased ion conductivity at lower tem-
reagents to execute selective electrophilic, peratures. Furthermore, the inert, but
nucleophilic, and radical substitutions unpolar solvent, petroleum ether, widely
and additions. used in alkali organic chemistry, cannot
Reactive donors can be generated ca- be applied in electrochemistry owing to its
thodically by reductive cleavage of halides missing dissociation power for supporting
to carbanions or by reduction of double electrolytes.
bonds to radical anions. Using these meth- The principle of electrochemical redox-
ods, two acceptors can be dimerized in one ‘Umpolung’ has been uniquely applied in
step by reductive ‘Umpolung’, for example, cyclization. Thereby, one of two donors
two molecules of acrylonitrile to adipodini- in the acyclic precursor is oxidized to an
trile – a reaction, which normally needs acceptor, whose reaction with the donor
two or more steps. leads to cyclization. The same holds for
On the other hand, highly devel- the cyclization by way of reduction of one
oped chemical techniques are available out of two acceptors [15].
3.4 Advantageous Electrochemical C,C-Bond Forming Reactions and Functional Group Interconversions 79
3.4 H
Selection of Advantageous Electrochemical Y +e, H+
Y
C,C-Bond Forming Reactions and 2 Y
Functional Group Interconversions
H
Y = CN, CO2Me, SO2Aryl, COR, NO2
Organic electrochemistry should prefer-
entially be used for those conversions, Yields: 28−95%
where the method has advantages over (1)
purely chemical reactions. In the follow- Aldehydes and ketones can be hy-
ing section, a selection of such conversions drodimerized to pinacols (Eq. 2) [34–37].
with yields that are mostly higher than 50% With aromatic carbonyl compounds, the
are given. yields and selectivities are mostly higher
than with aliphatic ones. The reaction
has been extended to imines (Eq. 2,
3.4.1
X = NAr, N–Bn) [38–41] and to hetero-
C,C-Bond Formation hydrodimerizations affording, for exam-
ple, γ -lactones (Eq. 3) [42–44].
There is a large variety of polar and rad- X +e, H+ XH 2

R
ical reactions, transition metal-catalyzed R1
and pericyclic conversions, that have been R1 R2 R1
R2
carefully developed with regard to scope, XH
selectivity, and yield. They are compiled in
R1 = aryl, alkyl, vinyl;
large compendia, for example, in [16–19],
R2 = H, aryl, alkyl;
and in series, for example [20, 21], and
are continuously improved and extended X = O, N-aryl, N-benzyl.
in timely research papers. This litera- Yields: 40−90 %
ture should be consulted in parallel with (2)
suggestions taken from electrosynthesis.
R3
Electrosynthesis is a clear alternative to +e, H+
OMe
chemical synthesis, when reactive inter- R1CH O +
mediates (see Sect. 3.3) such as radical
R2 O
ions, radicals, carbanions, or carboca-
tions are involved. The more advanta- R2 R3
geous are summarized in the following
sections.
At the cathode, olefins with electron R1 O O
deficient double bonds can be hydrodimer-
ized (Eq. 1). This reaction has been de- R1 = alkyl; R2, R3 = H, alkyl;
veloped for acrylonitrile [22] in a tech- Yields: 30−90 %
nical adipodinitrile synthesis [23] with a (3)
scale of more than 300.000 tons per Reductive ‘‘Umpolung’’ of acyclic com-
year. The scope of this hydrodimeriza- pounds with two acceptors allows efficient
tion has been substantiated with many single-step cyclizations by converting one
examples [24–33]. of the acceptors into a donor (Eq. 4) [15].
This has been applied to the cyclization Electron-rich olefins with substituents
of dihalides [45, 46], nonconjugated, un- Y = phenyl, vinyl, amino, or alkoxy can
saturated ketones [47] and esters [48], be coupled by anodic oxidation to tail–tail
oxoalkylpyridinium salts [49], aldehydes dimers being either deprotonated to dienes
and unsaturated nitriles [50], halides, and and/or substituted α to Y, depending on Y
unsaturated esters [51]. The ‘umpoled’ ac- and the reaction conditions (Eq. 6). Alkyl
ceptors, mostly radical anions or carban- substituted arenes can be dehydrodimer-
ions (see Scheme 1), can also be used in ized to diphenyls or diphenylmethanes
intermolecular reactions such as acylation, depending on the kind of substitution
alkylation, or carboxylation (Eq. 5). (Eq. 7).
a +e d Y Y −e
a′ a′ +
d −H+, NuH
Nu
a′
Y +
Y
a: C-halide [45, 46], C O [47, 52], Nu
+ Y
C N [49], CH CHCO2Me [53]; Y
a′: C-halide [45, 46], CH CH [47], Y: aryl [64], vinyl [65], OR [66],
RNH [67]; Nu: OMe; Yields 45−67%

C O [49, 54], CH CHCO2Me [53];
(6)
Yields: 23–100%
(4)
−e, −H+
a + a′ d + a′ 2
d a′
a: CH2 CHCO2Me [55], aryl [56], 71 % [68]
+ −e, −H+
N N [57], C N [58], 2
R CCl3 [59, 60];

+
a′: (RCO)2O [55], tBuNMe3 [56], 32 % [69]
Br(CH2)n Br [57], BuBr [58], (7)

A mirror image to the cyclization
RCH O [59], CO2 [61–63]. in Eq. (4) can be achieved by
reversing the polarity of one from two
Yields: 40–83% connected donors by anodic oxidation
(5) (Eq. 8) [15].
+ 3.4.2
Hd −e Ha Functional Group Interconversions
d′ d′
a There are a large variety of methods
−H+
for different FGIs in chemical synthe-
d′ sis that lead to the wanted products
d: aryl [70, 71, 72, 75], with high yield and selectivity. Many
of them are compiled in [18, 19] and
CH CHOEt [73, 76, 77], they are continuously improved, extended,
R′CH CH NR2 [74], and supplemented in timely communica-
tions.
d′: aryl [70, 71, 72, 74], Electrochemical FGIs can be classified
enol ether [76, 77], vinyl [75]; into four groups (Scheme 3):
Yields: 45−95% 1. anodic substitution and its cathodic

(8) counterpart, cathodic cleavage;
The application of radicals for C,C-bond 2. anodic dehydrogenation and cathodic
hydrogenation;
formation by way of coupling and addi-
3. anodic addition and cathodic elimina-
tion is shown in Scheme 2. Carboxylates
tion; and
are precursors for the anodically generated
4. anodic cleavage, where the cathodic
radical R• , see also Chapter 5 [78]. There,
reversal is a C,C-bond forming reaction,
R can bear different substituents; limita-
for example, hydrodimerization.
tions arise when they are in the α-position.
Furthermore, anions of CH-acidic com- CH-bonds for anodic substitution can
pounds have been applied with pKs-values be those in alkanes and aryl compounds as
up to 14 [79], because with this acidity well as those activated by an aryl, alkoxy,
they can be fairly simply handled with thio, amino group, or a double bond.
methanol as solvent; furthermore, Grig- For the anodic substitution of unac-
nard reagents have been oxidized to alkyl tivated CH-bonds, some fairly selective
radicals in diethyl ether [80]. For inter- reactions for tertiary CH-bonds in hydro-
molecular additions, fairly reactive olefins, carbons and γ −CH-bonds in esters or
such as styrene, butadiene [79, 81], elec- ketones are available [85–87]. However, in
tron deficient alkenes [82], or mediation some cases, a better control of follow-up
with Mn3+ have to be used to overcome oxidations remains to be developed. Chem-
the competing coupling of the radicals [83]. ically, a number of selective reactions are
These reactions afford synthetically inter- available, such as the ozone on silica gel for
esting additive dimers, where four build- tertiary CH-bonds [88], the Barton or Hoff-
ing blocks can be joined in one step mann–Loeffler–Freytag reaction for γ -
with specific head-to-head coupling of the CH-bonds [89], and for remote CH-bonds,
olefins. Intramolecular addition also tol- (i prop)2 NCl/H+ [90, 91], photochlorina-
erates less reactive alkenes as long as tion of fatty acids adsorbed on alumina [92]
the double bond is three atoms apart or template-directed oxidations [93].
from the radical to form a five-membered For activated CH-bonds, a wealth of
ring [84]. chemical methods are available, such
Anodic substitution,
−e, +Nu
C H C Nu
Cathodic cleavage,
+e, −Nu
Anodic dehydrogenation,
−e, −H
X X
Cathodic hydrogenation,
H H
+e, +H
Anodic addition, Nu
−e, +Nu
Cathodic elimination, Nu
+e, −Nu−
Anodic cleavage,
−e, −H+
X + X
(C,C : hydrodimerization),
X X
+e, +H+
H H
Scheme 3 Classification of electrochemical functional group interconversions (FGI’s).
as singlet oxygen, N -bromosuccinimde, by non-Kolbe electrolysis into products in

Br2 /hν, Pb(OAc)4 , or SeO2 [94]. Anodi- which the CO2 H group is regioselectively
cally, fair yields are obtained for CH- replaced by a nucleophile or a double
bonds activated by a vinyl, phenyl, or bond (see Chapter 6) [110–113]. This con-
alkoxy group [95–99], although sometimes version can be combined with specific
problems of regioselectivity occur. The rearrangements or fragmentations [110,
oxidation of N -acyl-N -alkylamines, which 114]. The comparable chemical conver-
leads to synthetically very interesting pre- sions, such as the Kochi reaction [115]
cursors of iminium cations [100–104], is or the Hofmann rearrangement [116], are
a unique electrochemical reaction. For more limited in scope.
the nucleophilic substitution of aromatic The cathodic cleavage of CX- to CH-
CH-bonds, electrochemistry has a clear ad- bonds can be achieved with a variety of
vantage over chemical conversions. At the substituents X, such as Hal, NR3 + , PR3 + ,
anode nucleophiles like OR, OCOR, and OTos, or epoxides. Generally, good yields,
CN can be introduced simply and in one a high potential selectivity, and often
step [105–109], while chemically, multi- good stereoselectivities are encountered
step procedures are necessary to achieve (see also Chapter 8) [117–123]. Chemical
this goal. reactions for similar conversions, which
Carboxylic acids can be regarded as are well worked out, especially with regard
compounds having a CH-bond with an in- to yield and selectivity, are the reduction
serted CO2 -group. They can be converted of tosylates with LiAlH4 and halides with
Bu3 SnH [124] or radical deoxygenations of improve the selectivity in anodic addition,
alcohols [125]. sometimes mediators like Pd2+ , Ce4+ , or
For the dehydrogenation of CH−XH Ru3+ are used (see Chapter 15) [127, 128].
structures, for example, of alcohols to ke- Chemical reagents that lead to similar con-
tones, of aldehydes to carboxylic acids, or versions include MnO4 − , OsO4 /N -methyl
of amines to nitriles, there is a wealth of an- morpholinoxide, Hal2 , and peracids [139].
odic reactions available, such as the nickel Cathodic elimination can remove a va-
hydroxide electrode [126], indirect electrol- riety of vicinal nucleophiles (X = Br [140],
ysis [127, 128] (Chapter 15) with I− , NO− 3, Cl [141], S-C6 H5 [142], or oxalate [143]) to
thioanisole [129, 130], or RuO2 /Cl− [131]. form a double bond. Controlled poten-
Likewise, selective chemical oxidations tial cathodic reduction allows the selective
(Cr(VI), MnO2 , MnO− 4 , DMSO/Ac2 O, elimination of vic-dihalides depending on
Ag2 O/Celite , and O2 /Pt) [94] are avail- the degree of alkylation [144]. Chemically,
able for that purpose. The advantages of these reductions are more limited in scope;
the electrochemical conversion are a lower they can be conducted with I− in DMF,
price, an easier scale-up, and reduced prob- with Zn, Mg, or Cr2+ [145].
lems of pollution. The cleavage of 1,2-diols can be inex-
The hydrogenation of C=X and C=C pensively achieved at a nickel hydroxide
double bonds can be achieved cathodically electrode [126], while chemically more ex-
and with a number of chemical reagents, pensive reagents such as Pb(OAc)4 or
such as catalytic hydrogenation, metal IO4 − must be used. The latter can be
hydrides, and dissolving metals [19]. Here, used as mediator for the indirect an-
the best method must be selected for each odic cleavage of starch [146]. Double bonds
individual case. The advantages of the can be cleaved at the anode to carboxylic
electrochemical method are the potential acids by applying the double mediator:
selective conversion at the cathode, the RuCl3 , IO4 − [147].
possibility of reducing carbon–heteroatom The conversion of heteroatoms to
double bonds in the presence of C=C different oxidation states, for exam-
bonds [132], the trans-hydrogenation of ple, NH2 → NO2 , -S- → -SO-, -SO2 - or
C=C bonds via radical anions [133] in NO2 → NHOH, NH2 is possible at the
contrast to the cis-hydrogenation with electrode. Of advantage, especially in the
catalytically transferred hydrogen, or the reduction of nitro functions, is the po-
potential selective reduction of the phenyl tential selective conversion to certain
group in the presence of an isolated double oxidation states such as the hydrox-
bond [134]. ylamino or amino group (see Chap-
Anodic addition converts enolacetates ters 7, 9, 10) [148–150].
into α-acetoxyketones or enones, depend- Cathodic cleavage and elimination com-
ing on the reaction conditions [135], con- bined with the possibility of varying the
jugated dienes into 1,2- or 1,4-dimethoxy reduction potential of protecting groups
alkenes [65], and hydroquinone dimethyl have proved to be mild and selective meth-
ethers into quinone bisketals [136, 137]. ods for deprotection. This way the tritylone
Anodic addition also affords products, group, which blocks alcohols with sim-
some of which are of industrial in- ilar chemoselectivity as the trityl group,
terest, such as propylene oxide [138a] but has a higher stability against acids,
or 1,4-dimethoxydihydrofuran [138b]. To can be cathodically removed [151]. The
β-polyhaloethyl group is cleaved at differ- metal, for example, Pb, Mg, Al, Hg, In,
ent potentials depending on the kind and Bi [165, 166]. Finally, a metal ion can be
number of halogens [152]. N-benzoyl or N- reduced to a highly reactive metal that
phenylsulfonyl protected amino acids can forms complexes with olefins or other lig-
be deblocked at the cathode [153]. Non- ands [167].
conjugated dienes having double bonds Electrochemical and chemical oxidative
with a different degree of alkylation can or reductive FGIs and C,C-bond form-
be selectively blocked with pyridinium ing reactions differ in some aspects.
hydroperbromide at the higher alkylated The first are heterogeneous reactions
double bond [154], and by potential selec- and mostly outer-sphere ET processes.
tive reduction of the tetrabromide at the The second ones are mostly homoge-
less alkylated one [144]. By controlled po- neous reactions and inner-sphere pro-
tential electrolysis, protecting groups can cesses. Outer-sphere ET mostly leads to
be selectively removed. This makes electro- more or less free reactive intermediates,
chemical deprotection [155, 156] a valuable for which the stereoselectivity of the fol-
supplement to chemical deprotection [157, lowing bond forming process is harder to
158]. Additionally, less interference with control. In inner-sphere ETs, the substrate
other functional groups is encountered forms simultaneously, with the change
than in chemical deprotection. of the oxidation state, a bond to the
Each oxidation generates at the an- hetero- or carbon atom of the oxidiz-
ode, electrophiles or protons, respectively, ing or reducing agent. These ETs are
and each reduction vice versa generates more sensitive to steric and electronic
nucleophiles or bases. With such electro- influences, which often leads to higher
chemically generated acids or bases, EGAs selectivities. This feature is exploited in
or EGBs, acid- or base-catalyzed reactions indirect electrochemical oxidations or re-
can be initiated (see chapter 14). EGBs ductions, where selective chemical oxi-
from probases, for example, azobenzene, dants/reductants are used as mediators
tetralkyl ethene tetracarboxylate, fluo- (see Chapter 15). Thereby, selectivities can
renes, or radical anions have been used for be improved, follow-up ETs suppressed,
deprotonation of aromatic hydrocarbons and second-order reactions shifted to first-
and subsequent carboxylation [159], or of order ones [168]. The smooth regeneration
a phosphonium salt to produce an ylide of the active mediator has been resolved
for a Wittig reaction [160]. EGAs produced in many cases (see Chapter 15); in oth-
in solvents of low nucleophilicity as conju- ers, for example, SmI2 [169], it is a matter
gated acids of the supporting electrolyte an- of intense ongoing research. In hetero-
ion have been used for the generation of ac- geneous electrochemical processes, the
etals from epoxides or ketones [161, 162]. reaction is confined to a more or less
Organometallic compounds can be gen- thin reaction layer (0.1 µm to 0.1 cm
erated at the electrode in three ways. An depending on the reactivity of the inter-
alkyl halide is reduced at an active cath- mediate). This leads to a higher concen-
ode, for example, Pb, Sn, which reacts tration of the reactive intermediate (102
with the intermediate radical [163, 164]. to 105 times higher), compared to the ho-
A Grignard reagent or an at-complex is mogeneous reactions of chemical redox
oxidized at an active anode and the in- reagents, and thus favors second- order
termediate radical reacts with the anode reactions.
3.6 Equipment 85
3.5 for reductions with methanol, tetrahy-

Working Out An Electroorganic Synthesis drofuran, or dimethylformamide. TEATos
and Bu4 NBF4 (tetraethyl tosylate, tetra-
First, one should determine how well elec- butylammonium tetrafluoroborate) have
trochemistry is suited for the planned proved to be useful as supporting elec-
synthetic step. For C,C-bond formations, trolytes. For a thorough treatment of this
this can be deduced from Schemes 1 and topic, see Chapter 2.
2 (Sects. 3.3 and 3.4 of this article). Ac- Products are then identified and roughly
cording to this information, electroorganic quantified by TLC, HPLC, GC, IR,
synthesis should be considered as favor- ESI/MS, GC/MS, and 1 H-NMR.
able for reductive and oxidative inter- and For optimization, the temperature is
intramolecular coupling reactions as well
extended down to −30 ◦ C and up to
as additions via radical ions, radicals, or
80 ◦ C, and the current density down
anions. Each FGI fitting into Scheme 3 is,
to 1 mAcm−2 . If unwanted oxidative or
in principle, suited for an electrochem-
reductive conversions have occurred, a
ical conversion. After this selection, a
potential controlled electrolysis (to prevent
literature search is made in the table of
over-oxidation or reduction) and a divided
contents of this book, in [170–174], and in
cell or a consumable anode (to prevent
an electronic search system to find timely
unwanted conversions at the counter
communications for reactions similar to
electrode) should be applied. If passivation
the given conversion. A closely related,
reported procedure should then be accu- (blocking of the surface of the working
rately reproduced. The conditions of the electrode by insulating films) is suspected,
examined reaction are then applied to the a more porous material for the working
given problem. In general, the following electrode, reversal of electrode polarity or
conditions are favorable: high substrate frequent cleaning of the electrode surface
concentration (∼0.5 mol l−1 ), undivided by polishing or heating to a red glow should
cell (provided substrate and product are be employed. These are just some hints;
fairly stable against the counter electrode), the topic is covered in depth in Chapter 2.
current controlled electrolysis at 50 to
100 mA cm−2 , a temperature of 0◦ to
50 ◦ C, and in the first electrolysis only a 3.6
50% conversion to suppress reductive or Equipment
oxidative follow-up reactions. For oxida-
tions, the materials suitable for the work- For the electrolyses, a cell and a DC
ing electrode are graphite, glassy carbon, power supply are needed. For a thorough
and platinum; and for reductions, the suit- coverage, see again Chapter 2. For most
able materials are graphite, glassy carbon, conversions, especially the exploratory
or a mercury pool. The materials that can ones, the author has used a double-walled
be used as counter electrodes are graphite beaker-type cell (Fig. 1).
or platinum as cathode or as anode, steel The cell is closed with a teflon stop-
as cathode, and aluminum as consum- per with small holes for the two current
able anode. For oxidations, it is suit- feeders, the Luggin capillary (to establish
able to start with the solvents: methanol, an electrolyte bridge between the refer-
acetonitrile, or CH2 Cl2 /CF3 CO2 H, and ence electrode and the working electrode
Insert for
reference electrode
Thermometer
Reflux condenser
Double-walled
cell
Luggin-
capillary
Electrodes
Fig. 1 Undivided beaker-type cell for potential controlled electrolysis.
in potential controlled electrolysis), a ther- The current consumed (measured in fara-

mometer, and gas inlet tube [not shown] days [F]) corresponds to F = current (in
(for purging the electrolyte with nitrogen). ampere) multiplied by electrolysis time (in
These parts are fastened in the stopper hours) multiplied by 0.0374.
with viton rings that are held in place by For a potential controlled electrolysis,
teflon plates, which are screwed to the top one needs a potentiostat [177] and a ref-
and the bottom of the stopper. V2A steel erence electrode. The Ag/AgCl electrode
rods, screwed into the graphite plates end- can be used as a reference electrode with a
ing in a holder for glassy carbon electrodes fixed potential. It is prepared from a silver
or screwed in a teflon frame that supports wire, which is covered with AgCl, when
thin platinum foils, served as current feed- employed as the anode in 2N HCl.
ers. A platinum wire sealed into a glass The reference electrode is connected
tube served as current feeder to the mer- with the cell via a glass tube (Luggin
cury pool electrode. capillary) filled with electrolyte, and the
For current-controlled conversions, a narrowed orifice of the tube is placed about
current-regulated DC source (up to 50V 0.1 to 0.3 mm in front of the side of the
and 2A, with voltage and current dis- working electrode that faces the counter
play) [175] or one or two car batteries (12 electrode. The potential between this point
to 24V) with a volt and ampere meter [176] and the surface of the working electrode is
or a regulated AC power source with a measured with a high resistance voltmeter
rectifier are sufficient as the power supply. that makes contact with the silver wire of
3.7 Some General Comments 87
the reference electrode and the current of electrochemical reactions with regard
feeder of the working electrode. It is to a potential selective conversion of an
this potential that the substrate and the electrophore is much better than that of
intermediates experience at the electrode chemical reactions. However, the chemo-
surface. The regulated DC source can selectivity, the regioselectivity, and espe-
be used as a potentiostat, when the cially the stereoselectivity are often inferior
current is manually adjusted in such to those of chemical reactions. The reasons
a way during the electrolysis that the are that chemical reactions proceed mostly
potential of the working electrode (against in a concerted way and are thus by na-
the reference electrode) maintains a given ture more sensitive to steric and electronic
value. This set-up can also be used to interactions than reactive intermediates
obtain current/voltage (i/U ) curves in the in electrode processes. Furthermore, the
electrolysis cell by changing the voltage lower temperatures that increase the se-
stepwise and recording the current. The lectivity are better attainable in chemical
voltage at the current steps in this curve conversions, and a much more profound
indicates at what potential the substrate is knowledge of the control of chemical reac-
converted and at what potential unwanted tions has been accumulated. The reagent
oxidations/reductions occur. This is the electron is cheap and readily available. Two
potential range in which the electrolysis moles of electron (2F) for the conversion of
should be conducted. The consumed 1 mole of substrate in a 2-electron conver-
current is recorded with a chemical or sion at a cell voltage of 5 volt corresponds to
electronic coulometer [178]. This chapter 0.27 kWh, which costs 0.03 Euro. Prices of
is written for organic chemists who have chemical reagents, on the other hand, are
not used electroorganic synthesis before. much higher except for oxygen, whose use,
It aims to facilitate the integration of the however, is limited due to its comparatively
reagent electron into synthesis by using low oxidation potential.
equipment that is either around in each The investment for equipment is some-
laboratory or can be prepared readily in what higher than for chemical reactors,
the workshop and by a glassblower or but an electrochemical reactor can be ap-
is commercially available at a reasonable plied to many more reaction types than
price. For a detailed introduction, see a chemical one. Technical electrolyses are
Chapter 2. mostly run in continuous flow reactors,
sometimes for years without change of the
electrodes, which saves personnel, main-
3.7 tenance, and solvent costs as compared
Some General Comments to chemical conversions, which are often
performed in batch reactors.
Organic electrochemistry fulfills favorably Electrochemical preparations are of-
the requirements defined for a good syn- ten easier to conduct than chemical
thesis (see Sect. 3.2). The ‘‘Umpolung’’ of conversions. Solubility problems, which
reactivity by ET saves steps because it al- frequently occur with inorganic redox
lows a one-step coupling of two donors reagents in organic solvents, are not en-
or two acceptors. In comparable chem- countered. On the other hand, the inert-
ical conversions, two or more steps are ness of the solvents and the lower attain-
necessary for that purpose. The selectivity able temperatures in chemical reactions
cannot be achieved to this extent in elec- sodium hydroxide, which leads to the co-
trolysis. To reach a sufficient electric production of sodium salts or sulfates as
conductivity, polar and, thus, more reactive waste [179, 180]. At the same time, in-
solvents are necessary for the electrolytes, organic acids and bases, necessary for
and the temperatures for practical reasons chemical production, are provided by this
cannot be lowered much below −40 ◦ C in process. An application of electrodialysis
preparative scale electrolyses. has been demonstrated in the prepara-
Workup of electrolyses is often easier as tion of methoxyacetic acid by oxidation
no products of chemical oxidants or reac- of methoxyethanol at the nickel hydrox-
tants need to be separated. Additionally, ide electrode [181]. Additionally, unwanted
in electrolysis a similar workup can be side products can be converted into the
used for a wide number of applications. wanted product. The economy of the
Furthermore, the scale-up of electrochem- process reduces the problem of waste sepa-
ical reactions is often easier to achieve ration and treatment. This is accomplished
than for chemical conversions. The elec- in the manufacture of chloroacetic acid
tron is a nontoxic reagent, which is not the by chlorination of acetic acid. There, the
case for many chemical reagents. Often side product, dichloroacetic acid, formed
used solvents and supporting electrolytes by overchlorination, is cathodically con-
in electrosynthesis such as methanol, wa-
verted to chloroacetic acid [182].
ter, and alkali or tetraalkylammonium salts
Also, the substrate in general needs no
are nontoxic. Expensive reagents are re-
additional atoms for activation because
cycled in catalytic amounts as mediators
the potential of the working electrode
in indirect electrolyses. Reaction condi-
can be adjusted by the power supply to
tions for electroorganic synthesis are, in
each electrophore for the activation of the
general, harmless. They are mostly con-
substrate by electron transfer.
ducted at room temperature and at normal
The broad scope of electrochemical
pressure. Reactive intermediates that un-
dergo exothermic reactions are not accu- C,C-bond forming reactions and FGIs is
mulated, but are immediately consumed demonstrated in many chapters of Vol-
after generation. ume 8 and partly summarized in Sect. 3.4.
Atom economy is high. As a reagent, no Furthermore, it should be mentioned that
compounds are needed and consequently at the electrode a synthetic building unit
none are produced as the electron is imma- can be used with several reactivities, be-
terial. This results in a greater advantage cause this can be changed via electron
of electrochemical reactions compared to transfer. In chemical preparation, build-
chemical conversions, namely, an effec- ing units are usually designed for only one
tive contribution to pollution control. The reactivity. While the reagent electron can
direct ET from the electrode to the sub- be applied to many diverse reactions, a
strate avoids the problem of separation chemical reducing or oxidizing reagent is
and waste treatment of the, frequently, mostly limited to a narrow selection of very
toxic end products of chemical reductions similar conversions. So for a chemical syn-
or oxidations. Furthermore, by electro- thesis, a number of different reagents have
dialysis, organic acids or bases can be to be either prepared in mostly multistep
regenerated from their salts without the procedures or have to be bought, mostly at
use of, for example, sulfuric acid or high cost.
Finally, the equipment to generate 16. B.M. Trost, I. Fleming, (Eds.), Comprehen-
the reagent electron for the majority of sive Organic Synthesis, Pergamon Press,
Oxford, 1991.
conversions in the milligram- to 100-gram
17. C.A. Buehler, D.E. Pearson, (Eds.), Survey of
scale consists (as shown in Sect. 3.6) of a Organic Syntheses, Wiley-Interscience, New
readily available and inexpensive, simple York, 1970, Vol. 1; 1977, Vol. 2.
cell and power supply. 18. Houben-Weyl, Methoden der Organischen
Chemie, Thieme, Stuttgart, Vol. 1–E 23.
19. R.C. Larock, Comprehensive Organic Trans-
References formations, 2nd ed., Wiley-VCH, New York,
1999.
1. J. Fuhrhop, G. Penzlin, Organic Synthesis: 20. Organic Reactions, Wiley, Vols. 1–61.
Concepts, Methods, Starting Materials, 2nd 21. Organic Synthesis, Wiley, Vols. 1–79.
ed., VCH, Weinheim, 1993. 22. M.M. Baizer, J. Electrochem. 1964, 111,
2. S. Warren, Organic Synthesis, The Dis- 215–222.
connection Approach, Wiley, New York, 23. D.E. Danly, C.R. Campbell in Technique of
1982. Electroorganic Synthesis (Eds.: N.L. Wein-
3. E.J. Corey, X.M. Cheng, The Logic of Chemi- berg, B.V. Tilak, A. Weissberger et al.),
cal Synthesis, Wiley, New York, 1989. Part III in Techniques of Chemistry, Wiley,
4. K.C. Nicolaou, E.J. Sorensen, Classics in New York, 1975, pp. 283–339, Vol. 5.
Total Synthesis, VCH, Weinheim, 1996. 24. M.M. Baizer, J.D. Anderson, J. Electrochem.
5. P. Renaud, M. Sibi, (Eds.), Radicals in Soc. 1964, 111, 223–226.
Organic Synthesis, Wiley-VCH, Weinheim, 25. M.F. Nielsen, J.H.P. Utley in Organic Elec-
2001, Vols. 1, 2. trochemistry (Eds.: H. Lund, O. Ham-
6. W. Oppolzer in Comprehensive Organic Syn- merich), 4th ed., Marcel Dekker, New York,
thesis (Eds.: B.M. Trost, I. Fleming), Perga- 2001, pp. 795–882.
mon, New York, 1991, p. 315, Vol. 5. 26. R.D. Little, M.K. Schwaebe, Top. Curr.
7. B. Cornils, W.A. Herrmann, (Eds.), Applied Chem. 1996, 185, 1–48.
Homogeneous Catalysis with Organometallic 27. P. Mikesell, M. Schwaebe, M. DiMare,
Compounds, VCH, Weinheim, 1996, Vols. 1, R.D. Little, Acta Chem. Scand. 1999, 53,
2. 792–799.
8. K. Chiba, T. Miura, S. Kim, Y. Kitano, 28. H.P. Utley, C.Z. Smith, M. Motevalli, J.
M. Tada, J. Am. Chem. Soc. 2001, 123, Chem. Soc., Perkin Trans. 2 2000,
11314–11315. 1053–1057.
9. J.H.P. Utley, S. Ramesh, X. Salvatella, 29. M.F. Nielsen, B. Batanero, T. Löhl, H.J.
S. Szunerits, M. Motevalli, M.F. Nielsen, Schäfer et al., Chem. Eur. J. 1997, 3,
J. Chem. Soc., Perkin Trans. 2, 2001, 2011–2024.
153–163. 30. J. Delaunay, A. Orliac, J. Simonet, J. Elec-
10. J.Y. Nedelec, J. Perichon, M. Troupel, Top. trochem. Soc. 1995, 142, 3613–3619.
Curr. Chem. 1997, 185, 141–173. 31. M.N. Elinson, S.K. Feducovich, A.A. Za-
11. C. Amatore, A. Jutand, J. Am. Chem. Soc. kharenkov et al., Tetrahedron 1995, 51,
1991, 113, 2819–2825. 5035–5046.
12. A. Galia, G. Filardo, S. Gambino, R. Mascol- 32. M. Wessling, H.J. Schäfer, DECHEMA
ino, F. Rivetti, G. Silvestri, Electrochim. Acta Monogr. 1992, 125 (Elektrochem. Stoff-
1996, 41, 2893–2896. gewinnung: Grundlagen Verfahrenstech.),
13. R. Scheffold, S. Abrecht, R. Orlinski, H.R. 807–813.
Ruf, P. Stamouli, O. Tinembart, L. Walder, 33. J.M. Kern, H.J. Schäfer, Electrochim. Acta
C. Weymuth, Pure Appl. Chem. 1987, 59, 1985, 30, 81–88.
363–372. 34. J.H. Stocker, R.M. Jenevein, J. Org. Chem.
14. E. Steckhan in Organic Electrochemistry 1968, 33, 294–297.
(Eds.: H. Lund, O. Hammerich), Marcel 35. R.E. Sioda, B. Terem, J.H.P. Utley et al.,
Dekker, New York, 2001, pp. 1103–1146. J. Chem. Soc. Perkin Trans. 1 1976, 561–563.
15. R.D. Little, K.D. Moeller, Electrochem. Inter- 36. D.W. Sopher, J.H.P. Utley, J. Chem. Soc.,
face 2002, 11, 36–42. Perkin Trans. 2 1984, 1361–1367.
37. J. Grimshaw, Electrochemical Reactions and 61. D.A. Tyssee, M.M. Baizer, J. Org. Chem.
Mechanisms in Organic Chemistry, Elsevier, 1974, 39, 2819–2828.
Amsterdam, 2000, pp. 330–370. 62. F. Koster, E. Dinjus, E. Dunach, Eur. J. Org.
38. H. Tanaka, T. Nakahara, H. Dhimane et al., Chem. 2001, 2507–2511.
Synlett 1989, 51–52. 63. H. Senboku, H. Komatsu, Y. Fujimura
39. L. Horner, D.H. Skaletz, Liebigs Ann. Chem. et al., Synlett 2001, 418–420.
1975, 1210–1228. 64. R. Engels, H.J. Schäfer, E. Steckhan, Liebigs
40. T. Shono, N. Kise, N. Kumini et al., Chem. Ann. Chem. 1977, 204–224.
Lett. 1991, 12, 2191–2194. 65. H. Baltes, E. Steckhan, H.J. Schäfer, Chem.
41. T. Sin, W. Li, A.K. Yudin, J. Comb. Chem. Ber. 1978, 111, 1294–1314.
2001, 3, 554–558. 66. D. Koch, H.J. Schäfer, E. Steckhan, Chem.
42. A. Fröling, Recl. Trav. Chim. Pays-Bas 1974, Ber. 1979, 107, 3640–3657.
93, 47–51. 67. D. Koch, H.J. Schäfer, Angew. Chem., Int.
43. T. Shono, H. Ohmizu, S. Kawakami et al., Ed. Engl. 1973, 12, 254–255.
Tetrahedron Lett. 1980, 21, 5029–5032. 68. K. Nyberg, Acta Chem. Scand. 1970, 24,
44. Asahi Chem. Ind. Co. Ltd., JP 82.108.274; 1609–1617.
Chem. Abstr. 1982, 97, 171368h. 69. K. Nyberg, Acta Chem. Scand. 1971, 25,
45. K.B. Wiberg, G.A. Epling, Tetrahedron Lett. 534–542.
1974, 1119–1122. 70. A. Ronlan, O. Hammerich, V.D. Parker, J.
46. S. Satoh, M. Itoh, M. Tokuda, J. Chem. Soc., Am. Chem. Soc. 1973, 95, 7132–7138.
Chem. Commun. 1978, 481–482. 71. L.L. Miller, R.F. Stewart, J.P. Gillespie et al.,
47. T. Shono, I. Nishiguchi, H. Ohmizu, J. Org. Chem. 1978, 43, 1580–1586.
M. Mitani, J. Am. Chem. Soc. 1978, 100,
72. T.W. Bentley, St.J. Morris, J. Org. Chem.
545–550.
1986, 51, 5005–5007.
48. S. Kashimura, Y. Murai, M. Ishifune et al.,
73. K.D. Moeller, Tetrahedron 2000, 56,
Acta Chem. Scand. 1999, 53, 949–951.
9527–9554.
49. R. Gorny, H.J. Schäfer, R. Fröhlich, Angew.
74. W. Eilenberg, H.J. Schäfer, Tetrahedron Lett.
Chem., Int. Ed. Engl. 1995, 34, 2007–2009.
1984, 25, 5023–5026.
50. R.D. Little, P. Mikesell in Organic Electro-
75. Y. Sun, B. Liu, J. Kao et al., Org. Lett. 2001,
chemistry (Eds.: H. Lund, O. Hammerich),
3, 1729–1732.
Marcel Dekker, New York, 2001,
pp. 725–764. 76. D.A. Frey, S.H.K. Reddy, K.D. Moeller, J.
51. S.T. Nugent, M.M. Baizer, R.D. Little, Tetra- Org. Chem. 1999, 64, 2805–2813.
hedron Lett. 1982, 23, 1339–1342. 77. D.L. Wright, C.R. Whitehead, E.H. Sessions
52. T. Nonaka, M. Asai, Bull. Chem. Soc. Jpn. et al., Org. Lett. 1999, 1, 1535–1538.
1978, 51, 2976–2982. 78. H.J. Schäfer, Top. Curr. Chem. 1990, 152,
53. J.P. Petrovich, J.D. Anderson, M.M. Baizer, 91–151.
J. Org. Chem. 1966, 31, 3897–3903. 79. H. Schäfer, A. Al Azrak, Chem. Ber. 1972,
54. J. Heimann, H.J. Schäfer, R. Fröhlich et al., 105, 2398–2418.
Eur. J. Org. Chem. 2003, 2919–2932. 80. H. Schäfer, H. Küntzel, Tetrahedron Lett.
55. T. Shono, I. Nishiguchi, H. Ohmizu, J. Am. 1970, 3333–3336.
Chem. Soc. 1977, 99, 7396–7397. 81. H. Schäfer, R. Pistorius, Angew. Chem., Int.
56. L.H. Kristensen, H. Lund, Acta Chem. Ed. Engl. 1972, 11, 841–842.
Scand. B 1975, 33, 735–741. 82. M. Chkir, D. Lelandais, J. Chem. Soc., Chem.
57. T. Troll, W. Elbe, Electrochim. Acta 1977, 22, Commun. 1971, 1369–1370.
615–618. 83. R. Shundo, I. Nishiguchi, Y. Matsubara
58. T. Shono, Y. Usui, T. Mizutani et al., Tetra- et al., Tetrahedron 1991, 47, 831–840.
hedron Lett. 1980, 21, 1351–1354 and 84. A. Matzeit, H.J. Schäfer, C. Amatore, Syn-
3073–3076. thesis 1995, 11, 1433–1444.
59. T. Shono, H. Ohmizu, N. Kise, Tetrahedron 85. L.L. Miller, V. Ramachandran. J. Org. Chem.
Lett. 1982, 23, 4801–4804. 1974, 39, 369–372.
60. H. Claus, H.J. Schäfer, Tetrahedron Lett. 86. A. Hembrock, H.J. Schäfer. Angew. Chem.,
1985, 26, 4899–4902. Int. Ed. Engl. 1985, 24, 1055–1056.
87. H.J. Schäfer in The Chemistry of Alkanes and 112. T. Nishitani, H. Horikawa, T. Iwasaki et al.,
Cycloalkanes (Eds.: S. Patai, Z. Rappoport), J. Org. Chem. 1982, 47, 1706–1712.
Wiley, New York, 1992, pp. 781–808. 113. J. Slobbe, J. Chem. Soc., Chem. Commun.
88. E. Keinan, Y. Mazur, Synthesis 1976, 1977, 82–83.
523–524. 114. R. Michaelis, U. Müller, H.J. Schäfer,
89. L. Stella, Angew. Chem. 1983, 95, 368–380; Angew. Chem., Int. Ed. Engl. 1987, 26,
Angew. Chem., Int. Ed. Engl. 1983, 22, 1026–1027.
337–349. 115. J.K. Kochi, J. Am. Chem. Soc. 1965, 87,
90. N.C. Deno, W.E. Billups, R. Fishbein et al., 2500–2502; J.K. Kochi, J. Org. Chem. 1965,
J. Am. Chem. Soc. 1971, 93, 438–440. 30, 3265–3271.
91. H.J. Schäfer, E. Cramer, Fat Sci. Technol. 116. J. March, Advanced Organic Chemistry, Wi-
1988, 90, 351–357. ley, New York, 1985, pp. 983–984.
92. L. Hinkamp, H.J. Schäfer, B. Wippich et al., 117. D. Pletcher, M. Razaq, J. Appl. Electrochem.
Liebigs Ann. Chem. 1992, 559–563. 1980, 10, 575–582.
93. R. Breslow, Acc. Chem. Res. 1980, 13, 118. M. Nagao, N. Sato, T. Akashi et al., J. Am.
170–177. Chem. Soc. 1966, 88, 3447–3449.
94. Several authors, in Comprehensive Organic 119. L. Horner, H. Röder, Chem. Ber. 1968, 101,
Synthesis (Eds.: B.M. Trost, I. Fleming), 4179–4183.
Pergamon, New York, 1991, Vol. 7, Chap. 2. 120. L. Horner, J. Haufe, Chem. Ber. 1968, 101,
95. S. Torii, Electroorganic Syntheses, Part I, 2903–2920.
Oxidations, VCH, Weinheim, pp. 75–87, 121. L. Horner, R.J. Singer, Chem. Ber. 1968,
223, 224, 246. 101, 3329–3331.
96. D. Degner, H. Siegel, H. Hannebaum, 122. K. Boujlel, J. Simonet, Electrochim. Acta
BASF AG, DE 2948455, 1981; Chem. Abstr. 1979, 24, 481–487.
1981, 95, 32 604. 123. S. Torii, T. Iguchi, S. Kurozumi, JP
97. T. Shono, A. Ikeda, Y. Kimura, Tetrahedron 63223191; Chem. Abstr. 1989, 110, 65731.
Lett. 1971, 3599–3602. 124. W.P. Neumann, Synthesis 1987, 665–683.
98. M. Mitzlaff, K. Warning, H. Jensen, Liebigs 125. W. Hartwig, Tetrahedron 1983, 39,
Ann. Chem. 1978, 1713–1733. 2609–2645.
99. K. Irie, J. Ban, Heterocycles 1981, 15, 126. H.J. Schäfer, Top. Curr. Chem. 1987, 142,
201–206. 102–129.
100. S.D. Ross, M. Finkelstein, R.O.C. Petersen, 127. E. Steckhan, Top. Curr. Chem. 1987, 142,
J. Am. Chem. Soc. 1966, 88, 4657–4660. 1–69.
101. K. Nyberg, R. Servin, Acta Chem. Scand. 128. S. Torii, Electroorganic Syntheses, Part I,
1976, B30, 640–642. Oxidations, Kodansha, VCH, Tokyo, Wein-
102. T. Shono, Y. Matsumura, K. Tsubata et al., heim, 1985, Chap. 11.
J. Org. Chem. 1986, 51, 2590–2592. 129. T. Shono, Y. Matsumura, J. Hayashi et al.,
103. T. Shono, Tetrahedron 1984, 40, 811–850. Tetrahedron Lett. 1979, 165–168.
104. T. Shono, Top. Curr. Chem. 1988, 148,(Elec- 130. T. Shono, Y. Matsumura, J. Hayashi et al.,
trochemistry III), 131–151. Tetrahedron Lett. 1980, 21, 1867–70.
105. L. Eberson, K. Nyberg, Acc. Chem. Res. 1973, 131. S. Torii, T. Inokuchi, T. Yukawa, Chem.
6, 106–112. Lett. 1984, 1063–1066.
106. L. Eberson, B. Helgee, Acta Chem. Scand. B 132. T. Pienemann, H.J. Schäfer, Synthesis 1987,
1978, 32, 157–161. 1005–1008.
107. Z. Blum, L. Cedheim, K. Nyberg et al., Acta 133. K. Junghans, Chem. Ber. 1973, 106,
Chem. Scand. B 1975, 29, 715–716. 3465–3472.
108. S. Andreades, E.W. Zahnow, J. Am. Chem. 134. R.A. Benkeser, S.J. Mels, J. Org. Chem.
Soc. 1969, 91, 4181–4190. 1969, 34, 3970–3974.
109. O. Hammerich, V.D. Parker, Acta Chem. 135. T.A. Shono, M. Okawa, I. Nishiguchi, J. Am.
Scand. B 1982, 36, 519–527. Chem. Soc. 1975, 97, 6144–6147.
110. S. Torii, Electroorganic Syntheses, Part I, Oxi- 136. N.L. Weinberg, B. Belleau, Tetrahedron
dations, VCH, Weinheim, 1985, pp. 57–71. 1973, 29, 179–185.
111. P. Renaud, D. Seebach, Angew. Chem., Int. 137. J.S. Swenton, Acc. Chem. Res. 1983, 16,
Ed. Engl. 1986, 25, 843–845. 74–81.
138. a) K.H. Simmrock, Hydrocarbon Proc. 1978, 160. R.R. Mehta, V.L. Pardini, J.H.P. Ut-
57, 105–113; Chem. Abstr. 1979, 90, 63490; ley, J. Chem. Soc., Perkin Trans. 1 1982,
H. Simmrock, Chem.-Ing.-Tech. 1976, 48, 2921–2926.
1085–1096. b) D. Degner, Technique of 161. K. Uneyama, A. Isimura, K. Fujii et al.,
electroorganic synthesis, Part III in Tech- Tetrahedron Lett. 1983, 24, 2857–2860.
niques of Chemistry (Eds.: N.L. Weinberg, 162. S. Torii, T. Inokuchi, Chem. Lett. 1983,
B.C. Tilak, A. Weissberger), Wiley, New 1349–1350.
York, 1982, pp. 251–282, Vol. V. 163. H. Ulery, J. Electrochem. Soc. 1972, 119,
139. Several authors, in Comprehensive Organic 1474–1478.
Synthesis (Eds.: B.M. Trost, I. Fleming), 164. M. Fleischmann, D. Pletcher, C.J. Vance,
Pergamon, New York, 1991, Vol. 7, Chap. 3. J. Electroanal. Chem. 1971, 29, 325–334.
140. J. Casanova, H.R. Rogers, J. Org. Chem. 165. US Pat. 3,007,858; Chem. Abstr. 1962, 56,
1974, 39, 2408–2410. 4526h.
141. A. Merz, Angew. Chem., Int. Ed. Engl. 1977, 166. H. Lehmkuhl, Synthesis 1973, 377–396.
16, 57–58. 167. H. Lehmkuhl, W. Leuchte, J. Organomet.
142. T. Shono, Y. Matsumura, S. Kashimura 1970, 23, C30–C32.
et al., Tetrahedron Lett. 1978, 19, 2807–2810. 168. E. Steckhan, Top. Curr. Chem. 1987, 142,
143. Nazar-ul-Islam, D. Sopher, J.H.P. Utley, 4–10, 1–69.
Tetrahedron 1987, 43, 2741–2748. 169. J.D. Parrish, R.D. Little, Abstr. Pap.–Am.
144. U. Husstedt, H.J. Schäfer, Synthesis 1979, Chem. Soc. 2000, 220th ORGN-019.
964–966. 170. J. Grimshaw, Electrochemical Reactions and
145. E. Bacciochi in The Chemistry of Functional Mechanisms in Organic Chemistry, Elsevier,
Groups, The Chemistry of Halides, Pseudo- Amsterdam, 2000.
halides and Azides, Suppl. D, Part 1 (Eds.: 171. T. Shono, Electroorganic Synthesis, Aca-
S. Patai, Z. Rapport), Wiley, New York, demic Press, London, 1991.
1983, pp. 161–201. 172. S. Torii, Electroorganic Syntheses, Part I:
146. V.F. Pfeifer, V.E. Sohns, H.F. Conway et al., Oxidations, Kodansha, VCH, Tokyo, 1985.
Ind. Eng. Chem. 1960, 52, 201–206. 173. H. Lund, O. Hammerich, (Eds.), Organic
147. U. St. Bäumer, H.J. Schäfer, Electrochim. Electrochemistry, 4th ed., Marcel Dekker,
Acta 2003, 48, 489–495. New York 2001.
148. P.E. Iversen, H. Lund, Tetrahedron Lett. 174. J. Volke, F. Liska, Electrochemistry in Organic
1967, 4027–4030. Synthesis, Springer, Berlin, 1994.
149. US Pat. 2.589.635; Chem. Abstr. 1952, 46, 175. The author has used a DC source from
4937g. Zentro-Elektrik (www.zentro-elektrik.de).
150. W. Löb, Z. Elektrochem. 1898, 4, 428–437. 176. D.A. Frey, N. Wu, K.D. Moeller, Tetrahe-
151. C. van der Stouwe, H.J. Schäfer, Chem. Ber. dron Lett. 1996, 37, 8317–8320.
1981, 114, 946–958. 177. The author has used potentiostats from
152. J. Engels, Angew. Chem., Int. Ed. Engl. 1979, Bank Electronic (www.bank-ic.de), Met-
18, 148–149. rohm (www.metrohm.de) and HEKA (www.
153. L. Horner, R.J. Singer, Liebigs Ann. Chem. heka.com).
1969, 723, 1–10. 178. The author has used a home built electronic
154. U. Husstedt, H.J. Schäfer, Synthesis 1979, coulometer (Dr. H. Luftmann, Univer-
964–968. sität Münster).
155. V.G. Mairanovsky, Angew. Chem., Int. Ed. 179. J.W. Blackburn, J. Air Waste Manage. Assoc.
Engl. 1976, 15, 281–292. 1999, 49, 934–942.
156. M.I. Montenegro, Electrochim. Acta 1986, 180. S. Resbeut, G. Pourcelly, R. Sandeaux et al.,
31, 607–620. Desalination 1998, 120, 235–245.
157. T.W. Greene, Protective Groups in Organic 181. M. Steiniger,H. Voss, BASF, DE 3620013
Synthesis, 2nd ed., Wiley, New York, 1999. A1, 1987; Chem. Abstr. 1988, 108, 175945n.
158. P.J. Kocienski, Protecting Groups, Thieme, 182. S. Dapperheld, R. Rossmeissel, Hoechst
Stuttgart, 1994. AG, EP 457320 B1; Chem. Abstr. 1992, 116,
159. R.C. Hallcher, M.M. Baizer, Liebigs Ann. 138732k.
Chem. 1977, 737–746.
93
4
Cathodic Reactions of
Hydrocarbons, Olefins, and
Aromatic Compounds
..
J urgen Heinze
..
Universit at Freiburg, Freiburg, Germany
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
4.2 Reductive Generation of Anionic Species . . . . . . . . . . . . . . . . . . . 95

4.2.1 Experimental Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
4.2.2 Redox Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
4.2.3 Electron-transfer Kinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
4.3 Chemical Reactions of Electrogenerated Anions . . . . . . . . . . . . . . 108

4.3.1 Homogeneous Electron Transfer . . . . . . . . . . . . . . . . . . . . . . . . 108
4.3.2 Electrophilic and Related Reactions . . . . . . . . . . . . . . . . . . . . . . . 110
4.3.2.1 Protonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
4.3.2.2 Alkylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
4.3.2.3 Acylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
4.3.2.4 Addition of CO2 and SO3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
4.3.3 Reductive Coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
4.3.4 Intramolecular Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
4.3.4.1 Conformational Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
4.3.4.2 Bond-breaking and Bond-making Reactions . . . . . . . . . . . . . . . . . 116
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
95
4.1 processes [6]. Techniques were developed

Introduction and improved to measure both the kinet-
ics of coupled chemical reactions [7] and
The electrochemical reduction of pure thermodynamic parameters such as redox
hydrocarbons without functional groups potentials of higher-charged aromatics [8,
is almost exclusively restricted to unsat- 9]. The discovery of the redox properties of
urated compounds. The reason is that conducting polymers in the year 1977 and
aliphatic hydrocarbons have extremely low later of the fullerenes [10, 11], gave new
electron affinities that render their reduc- impetus to the electrochemistry of unsat-
tion impossible, despite a gain of solvation urated hydrocarbons, initiating extended
energy within the stability limits of con- studies on the redox properties of these
ventional solvent-electrolyte systems. species [12–14].
Thus, electrochemical data involving
both thermodynamic and kinetic parame-
ters of hydrocarbons are available for only 4.2
olefinic and aromatic π-systems. The re- Reductive Generation of Anionic Species
duction of aromatics, in particular, had
already attracted much interest in the 4.2.1
late fifties and early sixties. The correla- Experimental Background
tion between the reduction potentials and
molecular-orbital (MO) energies of a se- Thermodynamic reduction potentials of
ries of aromatic hydrocarbons was one numerous aromatics were first measured
of the first successful applications of the by Hoijtink and van Schooten in 96%
Hückel molecular orbital (HMO) theory, aqueous dioxane, using polarography [15,
and allowed the development of a coher- 16]. These fundamental works were de-
ent picture of cathodic reduction [1]. The cisive tests of the HMO theory, showing
early research on this subject has been that the polarographic half-wave potentials
reviewed several times [2–4]. vary linearly with the HMO energies of
Later, during the golden age of mech- the lowest unoccupied molecular orbitals
anistic chemistry, interest focused on the (LUMO) of the hydrocarbons [1]. Hoijtink
elucidation of reaction paths of cathodi- et al. had already noticed that most aro-
cally generated species, including dispro- matics can be further reduced to their
portionations [5] and chemical follow-up respective dianions [17]. They proposed a
96 4 Cathodic Reactions of Hydrocarbons, Olefins, and Aromatic Compounds
two-step reduction scheme, where both re- A fundamental improvement in the fa-
dox potentials 1 and 2 are, on average, cilities for studying electrode processes of
separated by about 500 mV: reactive intermediates was the purification
technique of Parker and Hammerich [8,
E10 9]. They used neutral, highly activated alu-
−− −•
A−−−
−A (1) mina suspended in the solvent-electrolyte
system as a scavenger of spurious im-
E20
purities. Thus, it was possible to gen-
A−• −
−
−−−
−A
2−
(2)
erate a large number of dianions of
aromatic hydrocarbons in common elec-
However, their careful analysis also trolytic solvents containing tetraalkylam-
showed that most of the dianions were monium ions. It was the first time that
not stable in the polarographic or voltam- such dianions were stable in the timescale
metric timescale, and even less so after of slow-sweep voltammetry. As the pres-
bulk electrolysis, and underwent follow-up ence of alumina in the solvent-electrolyte
reactions with water or other electrophilic systems may produce adsorption effects at
impurities, details of which are discussed the electrode, or in some cases chemisorp-
in Sect. 4.3. tion and decomposition of the electroactive
Aprotic solvents such as acetonitrile [18, species, Kiesele constructed a new electro-
19] or dimethylformamide (DMF) [20–22] chemical cell with an integrated alumina
considerably improved the stability of the column [29].
radical anions but normally had little Heinze modified the technique by puri-
effect on the reactions of the more fying the solvent by transferring it under
basic dianions [22, 23]. The increased high vacuum from the electrochemical cell
irreversibility of the dianion formation to superactive alumina in a separate ves-
is probably because of the ability of sel [27, 28]. Such sophisticated methods
dianions to abstract protons even from made it possible to generate reversible
the solvent, or, by Hoffmann elimination, polyanions up to octaanions of aromatic
from the tetraalkylammonium salts that and olefinic hydrocarbons [27, 28, 30–33].
are common supporting-electrolytes in Further progress in stabilizing highly
aprotic solvents [24]. charged anions was achieved by the appli-
Progress in electrochemical instrumen- cation of unconventional solvents such as
tation soon stimulated the application of ammonia or dimethylamine at low temper-
more elaborated measurement methods atures. Using these solvents it was possible
than simple dc polarography, which facil- to observe the reversible generation of su-
itated studies of heterogeneous kinetics percharged anions at low scan rates in
and detection of follow-up reactions of voltammetric experiments [34, 35].
the electrogenerated species. Thus, con-
clusions originally drawn from the shape 4.2.2
and height of polarographic curves have Redox Properties
been amply confirmed by straightforward
diagnostic criteria in cyclic voltammetry [7, For the purpose of description, the electro-
25, 26], nowadays the standard method chemistry of hydrocarbons may usefully be
for mechanistic studies in organic electro- classified in three categories: benzenoid,
chemistry [27, 28]. nonbenzenoid, and olefinic hydrocarbons,
4.2 Reductive Generation of Anionic Species 97
each of which exhibit characteristic prop- 42, 43]. Rather surprisingly, the differ-
erties upon reduction. ences in half-wave potentials of hydro-
Benzenoid hydrocarbons have been carbons from one solvent to another are
studied in the greatest detail [2, 4, 36]. very small. This constancy in energy val-
In aprotic solvents they can be reversibly ues as well as slopes of correlation lines
reduced to their respective anions within widely varying solvents and supporting
out difficulties. Even the electrochemical electrolytes implies that solvation energies,
reduction of benzene in dimethoxyethane provided they are not small, change in the
has been described [37, 38]. In many cases same way from system to system.
the electrogenerated radical anions are As already observed by Hoijtink [17],
stable enough to allow the simultaneous nearly all benzenoid hydrocarbons can be
measurements of their extent solvent rereduced to their respective dianions – only
organization (ESR) spectra [39–41]. The benzene and naphthalene are exceptions.
most striking feature of benzenoid hy- In all experiments, these second reduc-
drocarbons is the excellent correlation tion steps appear approximately −0.55 ±
between their thermodynamic reduction 0.10 V negatively to the first reduction, pro-
potentials and the predictions of semiem- vided that the supporting electrolytes used
pirical π-electron theories, especially of were tetraalkylammonium salts. There-
the Hückel approximation (HMO). As the fore, these reduction potentials were also
thermodynamic reduction potentials are correlated with the LUMO energies of the
a measure of the electron affinities of HMO model [3]. It was suggested that the
the respective compounds, they can be energy difference of 0.55 eV corresponds
compared with the theoretically calculated to the repulsion energy between both elec-
energies in the simple MO picture, where trons in the LUMOs of the dianions [1],
additional electrons have been added to despite the differences in their structures.
antibonding MOs of the π-systems. There- On the other hand, quantum-mechanical
fore, assuming that the solvation energies calculations show that the repulsion ener-
for a series of aromatic hydrocarbons are gies are much larger. Dewar has calculated
constant, there should be a linear corre- values in the range of 5 eV [44]. The dis-
lation between the thermodynamic reduc- crepancy between experiment and theory
tion potentials (half-wave potentials E1/2 ) results from the fact that ion-pairing ef-
and the calculated energies mm+1 of the fects and solvation influences have been
lowest unoccupied MO (LUMO) in units of neglected in the calculation. Experimental
an effective β in the HMO approximation: data clearly reveal that counterion effects
E1/2 = −bmm+1 + C (3) that efficiently shield the negative excess
charge have in the past been underesti-
where b corresponds to an effective value mated and are considerably stronger for
of the resonance integral β and C is a condi- and polyanions than for radical an-
stant within a series of hydrocarbons. Inde- ions [44–47].
pendent voltammetric and polarographic In polar solvents such as DMF or ace-
measurements carried out in different tonitrile, the interaction increases in the
solvents such as 2-methoxyethanol, 96% order tetrabutylammonium < K < Na <
dioxane and DMF confirm the relation- Li and, consequently, reduction potentials
ship through excellent linear correlations shift in a positive direction [6, 48]. Ob-
with slopes b of approximately 2.40 [1, 20, viously, ion pairing is greatest for the
small lithium ions in agreement with the additional effects are observed, showing
prediction of Born’s equation [49]. In the influences of the supporting electrolyte
case of solvents with low dielectricity con- concentration and of the nature of the
stants the pattern is different, and ion cations [6]. In the tetraalkylammonium
pairing becomes dominant as the radius series the strongest (contact) ion pairs are
of alkali cations increases [47, 50, 51]. The formed by Et4 N+ , and KD is largest for
reasons for this behavior have not yet been that cation [9, 55].
studied in detail, but it has been proposed Drastic changes in the disproportiona-
that in ethereal solvents the solvation of tion constants occur when alkali cations
small cations remains stronger than that are used instead of tetraalkylammonium
of larger ones, and therefore ion pairing ions. Typically, the potentials of the radical
of potassium should be more pronounced anion formation are less affected than that
than that of lithium. of the dianion formation. In the presence
Ion-pairing effects may considerably of alkali cations, E 0 shifts may reach
influence disproportionation mechanisms values of more than 600 mV, which corre-
that involve homogeneous redox reactions spond to an increase in the K constant of
of anions to their respective dianionic and more than 10 orders of magnitude [52, 53].
neutral species (Eq. 4) [52, 53]. The electrochemistry of nonbenzenoid
hydrocarbons has attracted much inter-
2A−•
−−
−−−
2−
−A + A (4) est because their structures offer unusual
insights into π-electron systems, which
Disproportionation mechanisms have
undergo geometric changes upon reduc-
been proposed for protonation reactions
tion and obey both the Hückel 4n and
and intramolecular rearrangements (see
4n + 2 rules (Table 2).
Sects. 4.3.2 and 4.3.3) [54]. The prominent
The most widely studied examples are
feature is that follow-up processes at the
cyclooctatetraene (COT, 1) and its deriva-
level of the dianion can already take place at
tives. In such conventional aprotic solvents
potentials corresponding to radical anion
as DMF, dimethyl sulfoxid (DMSO), or ace-
formation. In order to evaluate data for
tonitrile containing tetraalkylammonium
disproportionation reactions it is necessary
salts, two distinct one-electron reduc-
to know the value of the disproportionation
tion waves are observed at approximately
equilibrium constant,
−1.64 V and −1.80 V vs. saturated calomel
[A2− ][A] electrode (SCE), with E 0 separations
KD = (5a) varying from −130 mV to −240 mV. [46,
[A−• ]2
56–60] In tetrahydrofuran (THF) and
RT
ln KD = E20 − E10 (5b) NH3 , this separation reduces further [61],
nF and in the presence of all alkali salts [62,
This can be determined from the differ- 63] even two-electron reduction waves with
ence in reversible potentials of the couples positive E 0 differences were obtained,
A/A−• and A−• /A2− (Eq. 5). indicating large disproportionation con-
In the case of benzenoid aromatics, KD stants. The unusually small separation of
values range between 10−9 and 10−13 the two redox steps in comparison to the
provided tetraalkylammonium salts have data of benzenoid aromatics was ascribed
been used as supporting electrolytes [9]. to the fact that the planar COT dianion
In solvents of low dielectricity constant, forms a 4n + 2 π-electron system that is
stabilized by its gain in Hückel resonance 4n + 2 π-systems. As predicted by the sim-

energy [64]. Obviously, strong ion-pairing ple MO theories, the transfer of an electron
effects additionally favor the formation of to a [4n]annulene should be energetically
the dianion [62, 63]. On the other hand, favorable because the electron is inserted
it was argued that a negative shift of the into a low-lying nonbonding orbital. The
first reduction step, leading to small E 0 further reduction to the dianion leads to
values, is caused by energy requirements a stabilized (aromatic) 4n + 2 π-system,
accompanying the transition from the which therefore should also be easily ac-
tube-shaped to the planar molecule. This cessible. In contrast, during the reduction
is supported by electrochemical results of an aromatic, [4n + 2]annulene electrons
obtained with methyl-substituted COT are injected into a LUMO with high en-
derivatives. Thus, all methyl-substituted ergy, and in the second reduction step an
derivatives due to a steric barrier are unstable 4n dianion is generated.
harder to reduce than (1) itself, and in Consequently, the reduction of [4n]annu-
1,2,3,4-tetramethylcyclooctatetraene (2) re- lenes should be observed at relatively
duction occurs at the extremely negative positive potentials with small E 0 sepa-
potential of −3.6 V (hexamethyl phospho- rations for the dianion formation, while
ric acid triamide, HMPA vs. SCE) [65]. In the reduction of the [4n + 2]annulenes
the case of phenyl-substituted COTs, the should occur at more negative potentials
steric demand is by and large energetically with large E 0 separations for the di-
compensated through the planarization of anion formation. This is exactly what is
the system and the subsequent resonance observed in (see Table 1). Although ben-
interaction between the phenyl moieties zene [37, 38], the classical Hückel aromatic
and the COT ring. Therefore, the reduction with 4 ∗ 1 + 2 = 6 π-electrons, is reduced
potentials are similar to that of an unsub- at −3.42 V (vs. Ag/AgCl), the reduction of
stituted (1). In addition, the resonance- the [8]annulene COT occurs at −1.81 V.
stabilizing effect upon the dianion is Similarly, the [16]annulene (3) [67, 68] is
sufficient to shift the second redox poten- more easily reduced than the correspond-
tial E20 positively to E10 , thus producing a ing [18]annulene (4) [69], although the
single two-electron reduction wave [59]. It reduction of the larger π-systems should
is interesting to note that the electrochem- be more favorable for electrostatic reasons.
istry of the doubly decked [8]annulene For larger annulenes, even the reduction
(=[22 ] (1,5)-cyclooctatetraenophane) also to tetraanions is possible [47, 75–77]. This
indicates some sterical strain [66]. The is especially favorable for the neutral
formation of the monoanion occurs at a 4n + 2 species, which, after the injection of
potential of −2.43 V (DMA, vs. Ag/AgCl). four electrons, reform a stabilized 4n + 2
It can be reduced up to its tetraanion at a π-system. On the other hand, the existence
potential of −3.22 V. of four excess charges in one molecule
The redox behavior of a number of gives rise to strong electron repulsion.
higher annulenes than (1) has been stud- It can only be shielded by ion pairing
ied during the past twenty-five years. that drives the formation of the tetraanion
The evaluation of their electronic prop- to a potential sufficiently positive for
erties has attracted much interest be- reduction to occur within the stability
cause it offers a good comparison of the range of the solvent-electrolyte system.
fundamental differences between 4n and Thus, the electrochemical reduction of
Tab. 1 Redox potentials E0 (in volt) for the reduction of aromatic and olefinic hydrocarbons
0
Compounds ER/R E0 − E0 2− E0 3− References
−
R /R2− R2 /R33
−
R /R4
Benzenea −3.42 – – – 35, 37

Naphthalenea −2.53 – – – 35
Anthracenea −2.04 −2.64 – – 35
Chryseneb −2.27 −2.77 – – 9
Coreneneb −2.07 −2.72 – – 9
1,2-benzanthraceneb −2.05 −2.67 – – 9
Phenanthrenea −2.49 −3.13 – – 35
Triphenylenea −2.42 −2.97 – – 35
Pyrenea −2.29 −2.91 – – 35
Biphenylc −2.68 −3.18 – – 12
p-terphenyla −2.40 −2.70 – – 35
o-terphenyl −2.62 −2.72 – – 70
Quaterphenyla −2.28 −2.455 – – 35
Stilbenea −2.26 −2.72 – – 35
Bianthryla −1.92 −2.14 −2.82 −3.17 35
Biphenanthryla −2.35 −2.51 −3.23 – 35
Decacyclenec −1.74 −2.14 −2.35 −2.68(−2.88) 27
2,2 -distyryl-biphenyla −2.12 −2.21 −2.81 −3.13 71
4,4 -distyryl-biphenylc −2.30 −2.52 −3.06 – 71
p-oligophenylenevinylene (n = 1)a −2.00 −2.24 – – 31
(n = 2)a −1.86 −1.97 −2.79 −3.10 226
(n = 3)a −1.85 −1.91 −2.46 −2.88 31
Acepleiadylenec −1.85 −2.51 −3.11 −3.14 47
COTd −1.81 −1.94 – – 59
[12]annulenee −1.35 −2.00 – – 72
1,7-methano[12]annulenef −1.51 −1.84 – – 73
15,16-dihydropyrene[14]annulene)g −2.22 −3.01 – – 64
[16]annulenef −1.27 −1.56 – – 67
[18]annulenef −1.60 −1.94 – – 69
Heptalenef −1.49 −2.19 – – 74
C60 h −0.98 −1.37 −1.87 −2.35 (−2.85, −3.26) 14
C70 h −0.97 −1.34 −1.78 −2.21 (−2.70, −3.10) 14
a Cyclic voltammetry was performed at a Pt electrode with solutions of 10−3 –10−4 M in substrate. All
potentials are expressed in V versus Ag/AgCl; solvent: dimethylamine-TBABr, temperature between
−40 and −65 ◦ C.
b DMF-Me NBr, potentials versus Ag/AgCl (corrected from SCE).
4
c THF-NaBPh or LiBPh , potentials versus Ag/AgCl, in brackets potentials for penta- and hexaanion
4 4
formation.
d ACN-TEAP, potentials versus Ag/AgCl (corrected from SCE).
e THF-TBAClO , potentials versus Hg pool.
4
f DMF-TBAClO , potentials versus Ag/AgCl (corrected from SCE).
4
g DMF-TBAClO , potentials versus Ag/0.1 M AgNO .
4 3
h Toluene/ACN-TBAPF , potentials vs. Fc/Fc+ at −10 ◦ C, in brackets potentials for penta- and
6
hexaanion formation.
Tab. 2 Structure formula of annulenes and cyclic conjugated systems (1–17)
(1)
(2) (3)
(4)
(6) (7) (9)

(8)
(5)
(13)
(10) (11) (12)
+ − −
(14)
(16)
(15) (17)
acepleiadylene (5) to its tetraanion was stabilization in the radical anion of

only achieved in THF in the presence (6). Analogously, dibenzonorcaradiene
of LiBPh4 as a supporting electrolyte [47]. (8) is easier to reduce than biphenyl,
Attempts to generate the same species in but harder to reduce than phenan-
the presence of tetrabutylammonium ions threne [41]. The electrochemical reduc-
were unsuccessful. tion of 1,6-dimethylbicyclo[4,4,1]undeca-
Several studies have been published con- 2,4,7,9-tetraene (9) was also interpreted in
cerning the problem of homoaromaticity terms of homoconjugation in the anions.
and its influence on reduction potentials. The reduction appears to proceed via an
The term ‘‘homoaromaticity’’ is applied to ECE scheme where the initial reduction
cyclic resonance-stabilized systems where produces an unstable radical anion, which
a carbon–carbon double bond is replaced undergoes a structural change, producing
by a cyclopropane ring, or a saturated another radical anion with a conjugatively
carbon atom is introduced into the conju- stabilized p-system. The second electron
gated chain. Paquette et al. investigated the transfer (ET) occurs more easily than the
reduction of cis-bicyclo- [6.1.0]-nona-2,4,6- first one, thus producing a typical ‘‘two-
triene (6) and similar derivatives [73]. They electron’’ reduction [78, 79].
found that it is reduced (−2.59, −2.79 V) Of the condensed nonbenzenoid aro-
more negatively than (1) but more eas- matics, azulene (10) has gained greatest
ily than cyclooctatriene (7) (−2.77 V), thus popularity [80]. Although it is an isomer of
proving a degree of homoconjugative naphthalene, its electrochemical behavior
differs markedly from its benzenoid coun- slowly producing a dimeric-species involv-
terpart. Azulene is reversibly reduced at ing coupling via the phenyl groups [87].
−1.62 V (vs. Ag/AgCl), while the reduction Similarly, 2,3 diphenylethyl-cyclopropenyl
of naphthalene takes place at −2.53 V [35, is irreversibly reduced in CH3 CN at Ep =
81]. Furthermore, the anion of azulene −0.04 V. On the other hand, the reduc-
is extremely stable against the attack of tion of trimethylcyclopropenyl occurs at
protons [81]. The bicyclus octalene (11) −1.32 V, which is in better agreement
has 14 π-electrons. H1 -NMR data show with the prediction of the Hückel the-
that it possesses a nonplanar structure ory [88–91]. Otherwise, relatively positive
with polyolefinic properties and therefore reduction potentials seem to be typical for
resembles its monocyclic relative COT. Po- most carbocations [92, 93]. The easy re-
larography and cyclic voltammetry reveal ducibility is probably caused by the excess
that it is reversibly reduced to the radi- positive charge.
cal anion at E1/2 = −1.67 V and, rather The discovery of the metal-like prop-
surprisingly, in a three-electron process erties of conducting polymers has once
at E1/2 = −1.70 V to its stable tetraan- again focused attention on the oxidation
ion [82, 83]. This unusual behavior can and reduction characteristics of aromatic
be only explained by assuming that the systems. It turns out that most of these
conducting materials consist of chainlike
energy gain from delocalization in the pla-
connected carbocyclic or heterocyclic aro-
nar 18 π-system is higher than torsional
matics [94–97].
and electronic repulsions. Other bicyclic
The simplest molecules in these se-
systems such as heptalene (12) [74] and
ries are dimers, followed by oligomers
pentalene (13) [84] can also be reduced
of increasing chain length and polymers.
to their respective anions. Nevertheless,
As the current–voltage curves of poly-
in comparison with equivalent monocyclic
mers are difficult to interpret, quantitative
p-systems such as (1), their reduction be-
information on the redox properties of
havior is still not properly understood. such systems was preferentially obtained
A further group of nonbenzenoid aro- from reduction experiments with dimers
matics is the series of odd-membered and defined oligomers. Redox data on
cations and anions such as cycloprope- dimers are available for biphenyl [12–14],
nium (14) and tropylium cations (15) bianthryl [53, 98, 99], biazulenyl [100] bi-
as well as cyclopentadienyl (16) and cyclooctatetraenyl [101], and dimeric [19]
cyclononatetracenyl anions (17). Regard- annulenes [102]. All species can be re-
ing the arguments for the properties of duced to at least their respective dianions.
Hückel-like 4n + 2 π-systems, all these In the case of bianthryl and bicyclooctate-
molecules should be energetically stabi- traene, even the formation of tetraanions
lized. Obviously, this is not fulfilled in has been observed. In general, the ob-
all cases. The tropylium cation (15) can served redox potentials of the monoanion
be reduced in a one-electron step to the formation differ significantly from those
tropyl radical even at E = +0.06 V vs. of the monomeric parent compounds
SCE [85, 86]. The radical is unstable and and shift to less negative values. This
rapidly dimerizes to bitropyl. The hep- is evidence of conjugative stabilization
taphenyl tropylium radical is stable on in the charged oligomeric unit [103]. On
the voltammetric timescale, but decays the other hand, large E 0 separations
between the redox potentials of the respec- anion has gained a considerable amount
tive mono- and dianions indicate strong of conjugative stabilization energy, while
electron repulsion between both elec- in the dianion, strong electron–electron
trophores. A typical example is biphenyl, repulsion dominates.
which is reduced to the radical anion at During the last decade, the concept of
−2.68 V and to the dianion at −3.18 V the oligomeric approach has been de-
(Fig. 1) [12–14, 35], whereas the reduc- veloped, which includes electrochemical
tion of the monomeric benzene occurs at studies of a great number of monodisperse
−3.42 V [37, 38]. Obviously, the biphenyl chainlike hydrocarbons. Voltammetric
5 µA
0.5 µA
0.2 µA
−3.5 −3.0 −2.5 −2.0 −1.5

E (vs. Ag/AgCl)
[V]
Fig. 1 Cyclic voltammograms for the reduction of biphenyl
(T = −70 ◦ C, v = 2 Vs−1 ); terphenyl (T = −40 ◦ C,
v = 100 mVs−1 ); and quaterphenyl (T = −5 ◦ C,
v = 100 mVs−1 ) in dimethylamine/0.1 M TBABr.
measurements carried out with several of the aromatic subunit, the overall
oligomers of the p-phenylenevinylene number of π-electrons, the π-topology,
(18, n = 1 − 6) [30, 31] and the p- and steric effects are important factors
phenylene [35] series, respectively, clearly for the redox behavior of all these species.
demonstrate that the reduction properties Thus in the series of oligoarylenevinylenes,
of such oligomers and polymers depend replacement of the phenylene unit by
on the chain length of the systems. Three larger arylene units enlarges the charge
effects are especially significant. First, the capacity of the respective systems. While
potentials of already existing redox states the p-oligophenylenevinylene (18) (n =
shift to less negative values when the next 1) with three phenylene units can be
higher homologue is reduced. Obviously, electrochemically reduced up to a dianion,
the redox energies of different states grad- the corresponding naphthalene derivative
ually approach a common convergence (19) (n = 1) reaches a trianion level and the
limit with increasing chain length. Sec- anthracene derivative (20) (n = 1) reaches
ond, the redox states degenerate pairwise even a hexaanion state [105–108].
with increasing chain length, and third,
p p =
in agreement with expectations, adding p
successive monomeric subunits in the p
n
molecular chain enlarges the number of (18)
accessible redox states (Fig. 1). However,
the energetic gap increases strongly be-
p =
tween the lowest and the highest charged
states. From these results, it becomes
clear that in conducting polymers like (19)
poly-p-phenylene, a reasonable number of
energetically low-lying redox states are de-
p =
generated, followed by redox states with
increasingly higher energies [12]. This ex-
(20)
plains the broad, plateaulike waves that
are so often characteristic of the potential An important reason for this phe-
range following the peaklike main wave in nomenon is the fact that the better the ex-
voltammetric experiments. cess charges in condensed aromatic units
Quite a large number of publications are stabilized, the larger the π-structure
that have appeared since that time support is. Of course, the energetic stabilization
these findings, but have also introduced of an excess charge in a large aromatic
new aspects that show the complexity of unit diminishes the trend for its delocal-
redox mechanisms in such systems [104]. ization and Coulombic repulsion effects
Very systematic studies have been carried along the chain. Therefore, the shift of
out by Müllen et al., who have varied, in the first redox potential dependent on
chainlike oligomers, the type and coupling the chain length is less pronounced for
position of the electroactive monomeric the naphthalene and anthracene deriva-
building blocks and the modes of linkage, tives than for the phenylene system or the
using both saturated and unsaturated pure oligoene chain, and, the separation
species with different lengths [105, 106]. between successive redox steps becomes
Their results clearly show that the size substantially smaller as the number of
Fig. 2 Reduction of
p-oligophenylenevinylenes (18), 0.2 µA
T = −65 ◦ C, v = 100 mVs−1 ; n = 3 in
DMA/TBABr, n = 4, 5 in THF/TBAPF6 ,
(dashed line: background current). n=3
(From Ref. [31].)
π-subunits increases (Fig. 2). A further in-

fluence on the redox properties results
0.1 µA
from the coupling pattern between the
vinylene and the arylene units. Mea-
surements on para-, meta-, and ortho- n=4
coupled phenylenevinylenes reveal that it
is more difficult to charge meta- and ortho-
homologues than the corresponding para-
homologues. However, the conjugative un-
coupling of two metagroups in a phenylene
0.005 µA
ring diminishes Coulombic repulsion, and
therefore the energetic separation between n=5
successive redox steps decreases.
The redox properties of oligo-p-pheny-
lenes change when sterically relevant
methyl groups exist in the central rings.
Thus, in comparison with the unsub-
stituted oligomers in methyl-substituted
homologues, for example (21), with four or
more phenylene units, the first reductive −3.5 −3.0 −2.5 −2.0 −1.5
redox step is shifted to a more negative po- E (vs. Ag/AgCl)
tential and a two-electron wave appears in [V]
the voltammetric response [109]. This can
be interpreted by assuming that, because
of steric hindrance, additional energy is high conductivity, up to 100 000 S cm−1 ,
needed to planarize the phenylene chain which emerges on oxidative or reductive
for the first electron transfer, and that the charging of the polymer [94–96, 110].
second electron is able to enter the then As already found by MacDiarmid [10],
flattened system at the same or even a PA can be reversibly reduced to a
more positive potential. polyanionic material.
Despite the great interest in PA, there
are only a few electrochemical studies
of monodisperse oligoene systems. The
reason is the high reactivity of doped alkyl-
(21)
substituted oligoenes in the presence of
Within the hydrocarbons containing nucleophiles or electrophiles. Normally,
olefinic double bonds, polyacetylene (PA) these oligomers consist of a carbon chain
is the most thoroughly studied system. The with alternating single and double bonds
great interest results from its extremely and two terminating groups, which are
equal in most cases. Thus, a t-butyl likely to occur for the longer polyenes
group [111–114] or, in the case of α- and (n ≥ 19).
β-carotenoids, a cyclohexenyl group [115, A further interesting point concerns
116], has been used, while phenyl or unusually small differences between the
other aromatic substituents have been reduction potentials of mono- and dianions
used as end groups in the so-called of some molecules containing olefinic
arylpolyenes [117]. The chain length n (n = double bonds. Although in trans-stilbene
number of double bonds in the conjugated the formation of the dianion occurs ap-
system) again determines the electronic proximately 500 mV negatively to the
properties of the oligomers. radical anion formation [35, 120], for
tetraphenylethylene the standard poten-
tials for the R/R − couple (ER/R
0
− ) and the
− 2− 0
R /R couple (ER− /R2− ) are very closely
n n spaced. The E 0 separation amounts in
(n = 0–4)
HMPA to −138 mV, in DMF to −35 mV,
(22) and in ACN reaches even positive val-
ues of approximately 150 mV [121–123].
A series of carotenes [118, 119] (22) Consequently, the disproportionation con-
(number of double bonds N = 5 and stant K varies within five orders of
higher) may serve as an illustration magnitude, a phenomenon mainly as-
of this redox behavior. For all related cribed to increasing ion pairing ongo-
states within the series, a strictly linear ing from HMPA to ACN [123]. Never-
dependence of the redox potentials versus theless, intermolecular phenomena alone
the chain length of the oligomers is are not sufficient to explain the dra-
observed (Fig. 3). As can be seen, the matic decrease of the E 0 separation in
reduction for the oligomer with N = 5 tetraphenylethylenes in comparison to stil-
starts with two well-separated one-electron bene. It is now generally accepted that
redox steps. With increasing chain length, structural changes involving twisting of
there are additional weakly separated the ethylenic bond and accompanying
redox pairs. The potential gaps in the the dianion formation are the main rea-
single pairs and between them decrease. sons for the energetic stabilization of
Thus, two-electron transfer steps are most the dianion of tetraphenylethylene [124].
Ered(1)
E (vs. Ag/AgCl)
−1.0 Ered(2)
−1.5 Ered(3)
−2.0 Ered(4)
−2.5
−3.0
0.00 0.05 0.10 0.15 0.20
1/N
Fig. 3 Apparent reduction potentials of (22) vs. 1/N (N: number of
double bonds), from CV measurements in dimethylamine/TBABr,
T = −60 ◦ C, v = 100 mVs−1 .
Similar effects are also observed with 9,9 - of heterogeneous charge transfer, addi-
bifluorenylidene [125]. tional double layer effects are operative,
which depend, inter alia, on type and con-
centration of the supporting electrolyte,
but may also be influenced by the elec-
trode material used as well as adsorption
phenomena. Theoretical concepts have
been developed by Hush, Marcus, and
(23) Dogonadze [130–134]. Applications of the
Marcus theory to problems in organic
A new class of conjugated hydrocar- electrochemistry have been discussed by
bons is that of the fullerenes [11], which Eberson [135]. As most studies on the re-
represent an allotropic modification of duction of hydrocarbons were carried out
graphite. Their electrochemistry has been in aprotic solvents in the presence of ex-
studied in great detail during the last cess supporting electrolyte, double-layer
decade [126]. The basic entity within this influences on electron-transfer kinetics
series is the C60 molecule (23). Because were usually regarded as less important [2,
of its high electron affinity, it can be re- 136]. Normally, the rates of heterogeneous
duced up to its hexaanion (Fig. 4) [14, 127]. ET to aromatic and olefinic hydrocar-
Solid-state measurements indicate that the bons are high. It is assumed that the
radical anion of C60 reversibly dimerizes. activation barrier is mainly caused by
NMR measurements confirm a σ -bond the solvent reorganization. Such reactions
formation between two radical anion moi- are termed outer-sphere processes. Reduc-
eties [128, 129]. tions of systems that require in addition
a large conformational energy change in
4.2.3 the transition state are rare [137]. The
Electron-transfer Kinetics most widely discussed example from this
class is the COT molecule (1), which ex-
Conversion of an oxidized species into hibits a slow heterogeneous ET for the
the reduced form and vice versa re- anion formation, while the rate between
quires the reorganization of the solvent the anion and the dianion is signifi-
in the immediate neighborhood of the cantly faster [56–58, 63]. In the literature
reactant, together with some structural it has been suggested that upon reduc-
changes within the reactant. In the case tion the tube-shaped ring passes through
10 µA
Fig. 4 Voltammogram for the

reduction of C60 in −0.5 −1.0 −1.5 −2.0 −2.5 −3.0 −3.5
toluene/acetonitrile
0.1 M TBABr; v = 100 mVs−1 , E versus Fe/Fe+
T = −10 ◦ C. (From Ref. [14].) [V]
at least a partially flattened transition state 4.3

to form a planar anion radical. The ex- Chemical Reactions of Electrogenerated
perimentally determined activation energy Anions
(10–11 kca mole−1 ), which is similar to
the activation energy of ring inversion With one or more electrons in antibonding
(13.7 kcal mole−1 ), has been interpreted orbitals, reduced hydrocarbons are a highly
as supporting evidence [136]. However, in- reactive species capable of both inter- and
dependent studies by Fry et al. [46] and intramolecular reactions. The preferred
Parker et al. [138] have shown that the rate pathway of the follow-up reaction depends
constant for the first reduction step in- not only on the electronic and steric
creased as the cation size of the supporting structure of the reduced species but also
electrolyte decreased from tetraheptylam- on its chemical environment, especially on
monium to tetramethylammonium. This the counterion and the solvent.
contradicts the assumption of pure struc-
tural reorganization effects during the 4.3.1
reduction of (1) and points to adsorp- Homogeneous Electron Transfer
tion phenomena of the electrolyte cations.
Moreover, in a very recent EPR investi- The most elementary follow-up reaction is
gation, homogeneous rate constants for the homogeneous ET to another solution
the COT− /COT electron self-exchange species, which may be identical with the
process were found to be close to the diffu- donor molecule itself [52]. The equilibria of
sion limit (∼109 M−1 s−1 ) [139]. It seems homogeneous ET reactions are governed
that the influence of structural reorga- by the standard potentials of the involved
nization on the activation process was redox couples and are easily calculated with
overestimated in earlier works. In a recent given data according to Eqs. (6–9):
paper, Evans discussed electron-transfer K
reactions of some fully α-methylated A1 −• + A2
−−
−−−
− A1 + A2
−•
(6)
cycloalkane-1,2-diones in which the con-
tributions of internal reorganization are E10
substantial [140]. In that case, both ho- A1 + e−
−−
−−−
− A1
−•
(7)
mogeneous (self-exchange) and hetero-
geneous electron-transfer rate constants E20
−
−− −•
are affected by the structural differences
A2 + e −−−
− A2 (8)
among these diketones. RT
Tetraphenylethylene is another example ln K = E20 − E10 (9)
F
of a slow charge transfer. Here, the rad-
ical anion formation is fast, whereas the The kinetics are much more complex and
second charge transfer is slow [121]. In depend on the reorganization of the molec-
agreement with the thermodynamic find- ular framework [141], the solvation shell,
ings, the second charge transfer suggests and the electrostatic interaction. A semi-
that considerable structural reorganization quantitative estimation of rate constants
occurs at the activation barrier of the sec- may be obtained with the well-known
ond reduction step. Nor is it yet clear as Marcus equation [142]. The calculated data
to what extent solvent reorganization also compare quite well with experimental val-
influences the activation energy [121]. ues. Most of the experimental hydrocarbon
4.3 Chemical Reactions of Electrogenerated Anions 109
data have been provided by Szwarc and his barrier may be circumvented by addi-
school [5]. The state of the art has been tion of aromatic hydrocarbons such as
discussed in an excellent review [135]. phenanthrene [145], anthracene [146], and
Homogeneous ET has to be taken into naphthalene [145]. These compounds are
account whenever dealing with electrode easily reduced at the cathode and transfer
reactions, as was pointed out by Mar- their excess electron to the organic halide.
coux [143]. It is of special importance when The resulting halide anion radical under-
the heterogeneous ET is slow, providing an goes a fast follow-up reaction. The whole
additional and more effective pathway to reaction sequence is as follows:
reduced species.
A + e−
−−
−−−
−A
−•
(11)
+e−
1 −−−→ 1−• (10a) A−• + PhCl
−− −•
slow −−−
−A + PhCl (12)
+e− PhCl−• −−−→ Ph• + Cl− (13)
1− −−−→ 12− (10b)
↑----------------
↓
12− + 1 −
←−−→ 2 ∗ 1−• (10c)
The homogeneous rate constant for the

second charge transfer in (1), similar to the
heterogeneous charge transfer, is consid-
erably larger than the first one. The differ-
ence greatly depends on the experimental
conditions. It has been shown by cyclic
voltammetry in super-dry THF/TBAPF6
that the first ET can be catalyzed by the
dianion of COT itself in a homogeneous
synproportionation (Eq. 10), giving rise to
a catalytic spike (Fig. 5). The mechanism
has been confirmed by digital simula-
tion [144]. 0.5 µA
Quite often the resulting anionic species
undergoes a fast follow-up reaction. Thus,
homogeneous ET becomes a crucial step
in many electrode reactions: a well-known
example is the cathodic reduction of or-
ganic halides. In mercury, heterogeneous
ET to most halides is slow. This kinetic
Fig. 5 Spike effect during the reduction

of (1) indicating an (autocatalytic)
homogeneous generation of the radical −1.0 −1.5 −2.0
anion of (1), cyclic voltammetry in
THF/0.1 M TBAPF6 , T = 20 ◦ C, E (vs. Ag/AgCl)
v = 100 mVs−1 . [V]
Ph• + A−•
−− − then be produced by diffusion-controlled
−−−
−Ph + A (14)
triplet–triplet annihilation. Emissions ob-
Ph− + H+ −−−→ Ph H (15) served at wavelengths other than that
of the main singlet have been ascribed
to excited dimers (excimers) [163, 164],
Regeneration of hydrocarbon in Eqs. (12 excited charge-transfer complexes (exi-
and 14) makes the process catalytic. plexes) [165–167], and fluorescent prod-
The reduction of organic halides in ucts of radical-ion decay. Acceptors in
the presence of aromatic hydrocarbons, electrochemiluminescence may be the cor-
the subject of detailed kinetic studies, responding hydrocarbon radical cations,
provide rate constants for the homoge- added alkyl halides [168] or benzoyl perox-
neous ET [147–150] and the follow-up ide [169, 170], or adventitious impurities,
reaction [151]. The theoretical basis for which need be present at only 10−7 M lev-
this kind of experiment (‘‘homogeneous els. The experimental technique for the
redox catalysis’’) was laid by Savéant’s method is demanding [171].
group in a series of papers during the
years 1978–80 [152–157]. Homogeneous 4.3.2
ET also plays an important role in the Electrophilic and Related Reactions
protonation of anion radicals [158].
When an anion radical undergoes het- 4.3.2.1 Protonation
erogeneous ET, formation of the neutral Under protic conditions, aromatic hydro-
molecule in the ground state is strongly carbons and compounds with activated
favored over formation of an excited double bonds usually undergo Birch-like
state [159, 160]. No such restriction applies reactions [172]. The reaction sequence has
to homogeneous ET, which, if sufficiently been elucidated by the classical work of
exothermic, may yield excited states of Hoijtink [15–17, 173, 174], who used the
hydrocarbons. One may naively suppose HMO theory to rationalize both chemical
that an electron is removed from the
and electrochemical steps.
bonding molecular orbital of highest en-
The anion radical produced by homo-
ergy to give either the first excited singlet
geneous ET is monoprotonated to give
or triplet; electrochemiluminescence [161]
a Wheland-like π-radical. It readily ac-
may then occur.
cepts another electron because its bonding
The emission observed is usually the
or nonbonding SOMO (single occupied
fluorescent band of the hydrocarbon, cor-
molecular orbital) always has a lower en-
responding to the decay of the first excited
ergy than the antibonding LUMO of the
singlet. The energy released by homoge-
parent hydrocarbon. The second ET prefer-
neous electron transfer is given by the
ably occurs by disproportionation [158].
difference between the redox potentials
In a fast follow-up reaction, the result-
of donor and acceptor plus a small en-
ing carbanion takes another proton to
tropy term [162], and in many cases of
eventually yield the final dihydroproduct
electrochemiluminescence falls short of
(Eqs. 16–20):
the energy needed to populate the singlet
state directly. In these ‘‘energy-deficient’’
A + e− −
−
−−−
−A
−•
(16)
cases, there is sufficient energy to popu-
late the lowest triplet state, and singlets can A−• + H+
−−
−−−
−AH
•
(17)
AH• + e− −
−
−−−
−AH
−
(18) be used [42, 184]. The attempt to cor-
relate rate constants with highest local
or charge densities failed [185]. Therefore,
Eberson suggested the application of the
AH• + A−•
−−
−−−
−
−AH + A (19) Dewar–Zimmermann rules [186].
Under highly protic conditions, the ma-
AH− + H+ −−−→ AH2 (20)
jor products of cathodic reductions of
cyclic conjugated hydrocarbons are usu-
If the reduction potential of the resulting
ally dihydro derivatives [56, 57, 187]. In
dihydroproduct is sufficiently positive, it
2-methoxyethanol, for example, naphtha-
can undergo another reduction cycle. One
lene yields 1,4-dihydronaphthalene [187]
of many examples is provided by the
reduction of benz[a]anthracene in 75% and COT mainly provides 1,3,6,-
aqueous dioxane [15–17, 175]. cyclooctatriene [56, 57].
Because of its general importance to These findings are in contrast to ther-
organic electrochemistry, the reaction modynamics favoring, in the case of
scheme just outlined has been the sub- naphthalene, the formation of conjugated
ject of detailed mechanistic studies [21, 1,2-isomers. Therefore, kinetic control has
176–182, 183]. As a model reaction, pro- to be assumed. The site selectivity for the
tonation of anthracene anion radicals by first as well as the second protonation
phenol in DMF has been selected. Of five step has been predicted by HMO theory.
limiting kinetic variants, ECErev , ECEirr , One approach refers to local charge den-
DISP1, DISP2, and DISP3, the favored sities [188]; the other one uses localization
pathway was found to be DISP1 [158]. energies as a reactivity index [189]. In any
It involves the protonation of the an- event, the inductive effect of the methylene
ion radical as the rate-determining step group, formed in the first protonation step,
(Eq. 17), followed by homogeneous ET has to be taken into account if two sites
between the anion radical and the pro- provide comparable reactivity indices.
tonated anion radical (Eq. 19), yielding These techniques proved to be success-
the monohydrogenated anion, which is ful for the majority of the hydrocarbons,
itself rapidly and irreversibly protonated but they failed for some compounds such
to the final dihydrogenated product. This as phenanthrene, terphenyl, or quater-
mechanism has been disputed because of phenyl. The failure has been interpreted
apparent deviations from predicted reac- by the effect of the electric field on the
tion orders [176–179]. Recently, it turned charge distribution [190]. Actually, these
out that the inconsistencies are largely due molecules have strongly anisotropic polar-
to the formation of homoconjugated com- izabilities. In a more recent study, it was
plexes between phenol and the phenolate demonstrated that the isomeric ratio also
anion [181]. Thus, DISP1 now seems to be depends on the counterion [191].
generally accepted. Under nominally aprotic conditions, 1,2-
The rate-determining step of the DISP1 protonation dominates in naphthalene.
mechanism, the protonation of the radical Reduction of naphthalene in anhydrous
anion, largely depends on its electronic acetonitrile containing tetraethylammo-
structure. As a guideline, LUMO en- nium p-toluenesulfonate yields 1,2-di-
ergies of the parent hydrocarbon may hydronaphthalene, which is subsequently
reduced to tetralin [192]. Similarly, reduc- formal ‘‘anti’’ addition of protons was ob-
tion of (1) in anhydrous DMF gives 1,3,5- served, whereas addition of phenol led
cyclooctatriene almost exclusively [56, 57]. to the prevalent formation of products,
The formation of the thermodynamically formally derived from ‘‘syn’’ protonation.
more stable products is most probably be- Obviously, steric effects and/or acidities of
cause of base-catalyzed isomerization. the proton donor and the dihydroproduct
An interesting situation arises from play an important role.
the reduction of CH-acidic hydrocarbons Quite often, ion pairing causes a sub-
because these compounds can undergo stantial positive shift of the reduction po-
self-protonation. Actually, a voltammetric tential. For electrostatic reasons, the shift is
investigation of 1,3-diphenyl-2-methylin- especially large for the formation of higher
dene and 4,5-methylenephenanthrene in valency ions. Therefore, with increasing in-
DMF/TBAP or DMSO/TBAP clearly interaction of the counterion, di- and polyan-
dicated a DISP1 mechanism, analogous ion formation becomes thermodynami-
to that described earlier [193]. Similar re- cally more favorable. Under these con-
sults have been obtained for variously ditions, cathodic reduction immediately
substituted indenes in which the stoi- produces dianions via disproportionation
chiometry is in perfect agreement with and heterogeneous ET. Because of their
a two-electron, two-proton reduction pro- high basicity, the dianions readily undergo
cess involving one-third starting mate- protonation. Such a dianion mechanism
was observed when tetraphenylethylene
rial under self-protonation conditions, the
was reduced in acetonitrile-TEAP in the
remaining two-thirds acting as an pro-
presence of water or alcohols. Kinetic mea-
ton donor [194]. Generally, under self-
surements led to a mixed-order rate law,
protonation conditions the DISP1 pathway
rationalized by the existence of a hydrogen-
operates (Eqs. 21–24) in which the proto-
bonded complex between the ion-paired
nation reaction between the radical anion
dianion and the proton donor [123, 124].
(AH•− ) and the neutral species (AH) is the
The classical Hoijtink mechanism and
rate-determining step.
the dianion mechanism have been ob-
served at electrodes with a high hydrogen
AH + e−
−−
−−−
−AH
−•
(21)
overvoltage, such as mercury. If mercury
−• −
AH + AH−
−
−−−
−AH2 + A
•
(22) is replaced by platinum with its low hydro-
gen overvoltage, a radical pathway seems to
AH2 • + AH−•
−−
−−−
−
−AH2 + AH (23) be favored [199], which is closely related to
− −
AH2 + AH −−−→ AH3 + A (24) catalytic hydrogenations of hydrocarbons.
Spectroelectrochemical experiments pro-
On the other hand, reduction of flu- vided evidence for an additional hydride
orene [195, 196] results in a homolytic mechanism (Eqs. 25–27) [200].:
cleavage of the CH bond (discussed in 2 H+ + 2e− −−
−−−
−H2 ads (25)
Sect. 4.3.4.2).
− −−− −
To study the stereochemistry of proto- H2 ads + e −−−H + Hads •
(26)
nation reactions, substituted indenes have A + H−
−− −
−−−
−AH (27)
been cathodically reduced in DMF/TBAP
with water or phenol being added [194, These results illustrate that the reaction
197, 198]. In the presence of water, a sequence and the stereochemistry of
cathodic hydrogenations are controlled synchronous shift of a single electron

by the solvent, electrolyte, proton donor, and bond formation (Eqs. 32 and 33). In
electrode material, and so on. Thus, addition, the generated anions may be
with increasing mechanistic knowledge, protonated (Eq. 34).
electrochemistry offers the chance to Because of these fundamental aspects,
realize highly selective hydrogenations. the mechanism of cathodically induced
The addition of protons is certainly the alkylations has been the subject of de-
most common ‘‘nucleophilic’’ reaction of tailed studies [147–150, 207]. In a stereo-
reduced hydrocarbon species due to the chemical investigation it was found that
almost ubiquitous availability of proton racemization is much more effective than
donors, which may or not be wanted. inversion. This result was interpreted as
However, under strictly aprotic conditions evidence of competition between the SET
it is also possible to add other electrophilic pathway and the SN 2 mechanism, with
reagents such as alkyl halides, acyl halides, SET being the more important route [207].
CO2 , and SO2 . The SET mechanism is represented in
Eqs. (28–34):
4.3.2.2 Alkylation A + e− −
−
−−−
−A
−•
(28)
The addition of alkyl halides to aromatic
anion radicals, generated by alkalimetal A−• + BX −−−→ A + B • + X −
reduction in ethereal solvents, was already (29)
known in the 1950s [201] and was reviewed A−• + B • −−−→ AB − (30)
by Garst in 1971 [202]. The first electro-
chemical analogue was observed by Lund A−• + B •
−−
−−−
−A + B
−
(31)
et al. [203]. These authors cathodically re- −• −
A + BX −−−→ AB + X •
(32)
duced hydrocarbons such as naphthalene,
anthracene, stilbene [145, 146], and pery- A−• + AB • −
−
−−−
−A + AB
−
(33)
lene [147–150] in the presence of alkyl − − +
B , AB + H −−−→ BH, ABH (34)
halides and isolated hydrogenated and
alkylated products. Similar reactions are The rate-determining step (Eq. 29) of the
observed when the halides are replaced by SET mechanism consists of an ET con-
ammonium or sulfonium [204]. certed with a cleavage of the carbon–halide
These alkylations can be looked upon bond in the alkyl halide, and resulting
as aliphatic nucleophilic substitutions, in the generation of an alkyl radical.
usually thought to proceed via SN 1, SN 2, or Numerous investigations have focused
hybrids of these mechanisms. However, in on the measurement of these rate con-
recent years more and more evidence for a stants [147–150]. As expected, the rate
single-electron transfer (SET) mechanism, constant increases when the redox poten-
represented in Eqs. (28–31), was obtained, tial of the aromatic compound becomes
and it was suggested that SN 2 and SET more negative. The coupling step between
are just limiting cases of the same single- alkyl radicals and aromatic anions is fast,
electron transfer mechanism [205, 206]. with rate constants at the level of dif-
The SET pathway involves first a transfer fusion control. This indicates the lack
of an electron from the nucleophile to the of significant activation barriers, which
electrophile followed by bond formation, consequently results in insensitivity to
whereas the SN 2 reaction involves a structural differences in the alkyl radical
and in the aromatic radical anion [208]. acetylene [217–220]. The mechanism is
Moreover, radical anions with very differ- assumed to be analogous to that for
ent redox potentials (EA0 = 0.9 V) couple protonation, the essential steps being nu-
with primary radicals with approximately cleophilic addition by an anion radical
the same rate constant. The competing and subsequently by an anion [221]. 1,4-
SN 2 mechanism Eqs. (32 and 33) may be Addition to naphthalene suggests that
favored if the reacting species are not too carboxylation is kinetically controlled; for-
sterically hindered, and the driving force mation of dihydromonocarboxylates in-
for an electron-transfer reaction is low. dicates competition with protonation.
In general, the more positive the redox Mechanisms involved have CO2 −• to be
potential of the aromatic compound is
considered for those hydrocarbons that
or the poorer the alkylhalide is an elec-
are reduced at more negative poten-
tron acceptor, the more important the SN 2
tials than CO2 [222], and for the elec-
mechanism becomes [209].
troinactive norbornadiene, which gives 3-
4.3.2.3 Acylation nortricyclenecarboxylic acid [223]. Chem-
Formally related reactions are ob- ically CO2 −• formed is known to
served when anthracene [210] or arylole- undergo typical radical addition reac-
fines [211–213] are reduced in the pres- tions [222, 224]. Like CO2 , SO3 adds
ence of carboxylic acid derivatives such as to reduced anthracene to give 9,10-
anhydrides, esters, amides, or nitriles. Un- dihydroanthracenebissulfonate [215, 216].
der these conditions, mono- or diacylated
compounds are obtained. It is interesting 4.3.3
to note that the yield of acylated products Reductive Coupling
largely depends on the counterion of the re-
duced hydrocarbon species. It is especially Cathodically reduced hydrocarbons not
high when lithium is used, which is sup- only undergo homogeneous ET and nucle-
posed to prevent hydrodimerization of the ophilic attack but also coupling reactions
carboxylic acid by ion-pair formation. In resulting in hydrodimerization and poly-
contrast to alkylation, acylation is assumed merization.
to prefer an SN 2 mechanism. However, it Reduction of stilbene [18] or dipheny-
is not clear if the radical anion or the dian- lacetylene [214] in DMF yields 1,2,3,4-
ion are the reactive species. The addition tetraphenylbutane, whereas phenan-
of nitriles is usually followed by hydrolysis threne [214] provides 9,9 ,10,10 -tetra-
of the resulting ketimines [211–213]. hydro-9.9 -biphenanthrene. Hydrodimer-
4.3.2.4 Addition of CO2 and SO3 ization was also observed with benzalfluo-
In the pioneering papers of Wawzonek rene [225]. If DMF is replaced by acetoni-
et al. [18, 214] it was demonstrated that trile, protonation completely dominates
CO2 can be added to cathodically re- hydrodimerization [18]. In carefully dried
duced hydrocarbons to yield dihydrodi- ethers, using alkali or alkaline earth
carbonylates. Examples of this kind of metals salts as supporting electrolyte,
reaction include naphthalene [215–220], 1,1-diphenylethylene can be reduced ca-
anthracene [18], 9,10-diphenylanthracene thodically to give stable solutions of
[18], phenanthrene [215, 216], butadi- 1,1,4,4-tetraphenylbutane dianions [226].
ene [217–220], stilbene [18], and diphenyl These dianions can be cleaved by flash
photolysis in the presence of excess 1,1- polymerization. Styrene is polymerized in

diphenylethylene to give transient anion ethers by alkali metal reduction [242] or
radicals of 1,1-diphenylethylene. Kinetic addition of cumyl potassium [243]. The
analysis of the subsequent recombination mechanism of ET-induced polymerization
confirmed the postulated radical–radical was extensively studied by Szwarc and his
mechanism; the rate constant was found school [244–246]. It turned out that the
to be 0.5 * 109 M−1 s−1 [227]. 9-Cyanoan- first step is dimerization of the styrene
thracene undergoes a reversible elec- anion radical, usually obtained by addi-
trodimerization with almost no side re- tion of sodium naphthalene. Under aprotic
actions, making a perfect model com- conditions, the resulting dianion adds to
pound [228–233]. Again, it turned out that monomers, forming polymeric ‘‘living an-
the dimerization follows a radical–radical ions.’’ It is interesting to note that the rate
mechanism. It is also interesting to note of the polymerization largely depends on
that water accelerates the dimerization. the counterion.
This effect was rationalized by specific sol- With conventional techniques and elec-
vation [233]. A careful study of the dimer- trolytes, it was not possible to obtain living
ization kinetics of 9-cyanoanthracene in anions because they are rapidly protonated
different solvents and at low temperatures by tetraalkylammonium salts and residual
gives evidence that the coupling reaction water. The first report of the production of
is diffusion controlled and that its rate living polymers by an electrolytic method
constant increases with increasing polar- has to be attributed to Yamazaki et al. [247],
ity of the solvent as predicted by the who used tetrahydrofuran as solvent, and
Debye–Smoluchovsky theory [234, 235]. It LiAlH4 or NaAl(C2 H5 )4 as electrolyte for
should be noted that several authors have the polymerization of α-methylstyrene. A
suggested a more complex reaction pat- similar technique was used to polymerize
tern, which at least involves a two-step styrene as well as derivatives [248–252].
mechanism [236, 237]. A final decision on The suggested mechanism agrees with the
the validity of these different reaction paths pathway described earlier.
will be a task of future research.
Many alkenes, activated by electron- 4.3.4
withdrawing groups, readily undergo hy- Intramolecular Reactions
drodimerizations. The best-known exam-
ple is the electrodimerization of acryloni- For many years, intramolecular reactions
trile, the base of the commercial Monsanto such as conformational changes, bond
process [238–240]. Evidence is presented cleavage, bond formation, and valence
there that the essential step is a cou- isomerizations have been observed only
pling of two radical anions (radical–radical when hydrocarbons were reduced with al-
route). In a very recent study, A. J. Bard kali metals in ethereal solvents. In most
has shown, using the scanning electro- electrochemical experiments, these reac-
chemical microscope (SECM) technique tions were dominated by the electrophilic
(see Volume 3, Chapter 3.3), that only processes already described. However,
the radical anions of acrylonitrile dimer- progress in experimental techniques [8, 9,
ize (radical–radical route) [241]. Sterically 27–29] has made these reactions accessible
less demanding arylalkenes and dienes to electroanalytical investigations, provid-
undergo not only dimerization but also ing new mechanistic insight.
4.3.4.1 Conformational Changes diarylalkanes in ethereal solvents was

In recent years it has become increasingly already observed by Ziegler and Thiel-
obvious that ET is frequently accompanied mann in the 1920s [258]. As was shown
by conformational changes. The inter- by Lagendijk and Szwarc [259] for 1,2-
conversion may precede or follow ET; di(α-naphthyl)ethane, the primary anion
the majority of these processes have to radical undergoes homogeneous dispro-
be classified as CE (as yet this mech- portionation that is supported by ion
anism has not been observed in the pairing. The resulting dianion decomposes
hydrocarbon series), EC, EEC, or ECE by the fission of the CH2 –CH2 bonds into
mechanisms, whereas only a few sys- the salts of α-naphthylmethyl carbanions.
tems follow an EE pathway. An example Similarly, 9,9 -bianthryl can be cathodi-
for an EC process is the interconver- cally cleaved into anthracene and 9,9 -
sion of the anion radical of cis-stilbene, dihydroanthracene plus small amounts of
which is quite slow on the voltammetric reduced dimers. The dianion mechanism
timescale [120], whereas cis-azobenzene is quite slow, whereas the tri- and tetraan-
anion radicals isomerize very rapidly [253, ions are supposed to decay rapidly [260].
254]. Tetraphenylethylene undergoes two ESR spectroscopical investigations of
closely separated reversible additions of the anion radical of fluorene indicated a
one electron [122, 255, 256]. The small first-order decay, and it was concluded
difference of standard potentials, equiva- that the CH bond undergoes homolytic
lent to a high disproportionation constant cleavage [261]. Voltammetric studies of
(see Eq. 5), has been interpreted as in- fluorene in DMF reached the same
terconversion from an almost planar to conclusion [195].
an orthogonal conformation when go- The thermal and photochemical ring
ing from the neutral molecule to the opening reactions of cyclobutene are
dianion [257]. The thermodynamics and the classical examples of pericyclic pro-
kinetics of ET-induced interconversions cesses [262]. In 1976, Bauld et al. described
of substituted tetraphenylethylenes have an ET-induced analog [263]. They observed
been studied in great detail [141]. Reduc- that benzo- and phenanthrocyclobutene
tion of 1,6-dimethylbicyclo[4.4.1]undeca- undergoes ring opening upon alkali metal
2,4,7,9-tetraene appears to proceed via an reduction and suggested an ECE pathway.
ECE scheme where the initial reduction A voltammetric study of 1,2-tetrahydro-
gives an unstable radical anion, which un- 1,2-diphenylcyclobutanephenanthrene in
dergoes a structural change, giving another THF-NaBPh4 confirmed this mechanism.
anion with a conjugatively stabilized π- However, it turned out that the rate
system [78, 79]. Conformational changes of the ring opening largely depends on
concurrent with ET (EE pathway) are ob- the counterion. If ion pairing is pre-
served upon reduction of (1), as cited vented by addition of 15-crown-5, the
earlier. This emerging field was reviewed reaction rate slows down dramatically.
by Evans and O’Connell [141]. At −50 ◦ C the anion radical of the Z
isomer becomes stable on the voltam-
4.3.4.2 Bond-breaking and Bond-making metric timescale, whereas the dianion
Reactions exhibits a fast ring opening [71, 264]. Two-
Reductive cleavage of carbon–carbon electron reduction [61] or oxidation [265]
bonds upon alkali metal reduction of of 1,3-dimethylidenecyclobutanes yields
bicyclo[1.1.0]butanes. Cyclic voltamme- formation takes place at the di- and tri-
try of 2,4-di-9H-fluoren-9-yliden-1,1,3,3- ionic level, which is comparable with a
tetramethylcyclobutane in DMF at low radical–radical coupling (RR route, EEC
temperatures demonstrated that bond for- mechanism) [71]. The experiments are ev-
mation proceeds via an EEC mecha- idence that RS (radical substrate) coupling
nism; the rate constant was found to be is generally improbable for ionic dimer-
20 s−1 [264]. ization reactions. At low temperatures,
ET-induced cycloadditions of polycyclic the coupling rate between the negatively
olefins and cycloreversions of cyclobutane charged styryl units slows down and the
species have been studied by ESR spec- tetraanion of the starting species can be
troscopy [266]. Upon chemical and electro- obtained. Again, it turns out that ion-
chemical reduction, 2,2 -distyrylbiphenyl pairing effects favor the formation of
rearranges by intramolecular coupling into the bis-benzylic intermediate. Thus, the
a ‘‘bis-benzylic’’ dihydrophenanthrene first-order intramolecular coupling step
dianion B 2− (Scheme 1), which can be between the negatively charged styryl units
either protonated to a 9,10 -dibenzyl-9,10- is significantly faster in THF/NaBPh4 than
dihydrophenanthrene or oxidatively cou- in the presence of additional 15-crown-
pled to a cyclobutane species. It is interest- 5 or in DMA/TBABr [71] (Scheme 1,
ing to note that the intramolecular bond Fig. 6).
+e +e +e +e
−e −e −e
A 3− −e
A 4−
−2, 12 V −2, 12 V −2, 81 V −3, 13 V
hv Na+ (Li+) Na+ (Li+)
+e +e +e
−e −e B 2− −e B 3−
−1, 35 V −2, 98 V
hv Na+ (Li+)
+e +e
−e −e
C 2−
−2, 60 V < −3, 0 V
Scheme 1 ET-induced cycloaddition of 2,2 -distyrylbiphenyl.

0.2 µA
(c)
1 µA
(b)
5 µA
(a)
−3.5 −3.0 −2.5 −2.0 −1.5 −1.0

E versus Ag/AgCl
[V]
Fig. 6 Reduction of 2,2 -distyrylbiphenyl (a, b) and
1,2-tetrahydro-1,2-diphenylcyclobutanephenanthrene (c) see
[Ref. [71]; (a) in THF/NaBPh4 , v = 200 mVs−1 , T = 0 ◦ C (b, c) in
DMA/TBABr, v = 100 mV s−1 , T = −60 ◦ C.
1-Arylindenes undergo sigmatropic 1,5- dianion is formed via homogeneous

shifts, induced oxidatively [267], ther- disproportionation, thermodynamically fa-
mally [268], photochemically [269], and re- vored by ion pairing and kinetically sup-
ductively [270]. The reductive rearrange- ported by the fast follow-up reaction. When
ment of 1,1,3-triphenylindene, yielding ion pairing is suppressed by an applica-
the dianion of 1,2,3-triphenyl-2H-indene, tion of low temperatures or the addition of
has been the subject of voltammetric sodium complexing 15-crown-5, the anion
investigations in DMF-TBAP [271]. The radical becomes persistent and the reac-
reaction follows an EEC or EDisp C tive dianion species has to be generated via
pathway. heterogeneous ET at much more negative
At room temperature in the pres- potentials. The same results are obtained
ence of Na+ cations, the rearranging when the bulky tetrabutylammonium
ion is used as a counterion [271]. Re- 18. S. Wawzonek, R. Berkey, E. W. Blaha et al.,
placing 1,1,3-triphenylindene with 1- J. Electrochem. Soc. 1955, 102, 235.
19. A. C. Allison, T. A. Gough, M. E. Peover,
methyl-1-phenylindene or 1,2-dihydro-
Nature 1963, 197, 764.
1,1 -spirobiindene, the anion radical un- 20. A. Streitwieser, I. Schwager, J. Phys. Chem.
dergoes quite an unusual cleavage of 1962, 66, 2316.
the alkyl–aryl bond, whereas the dian- 21. R. Pointeau, Ann. Chim. 1962, 7, 669.
ion rearranges in the same manner as 22. K. S. V. Santhanam, A. J. Bard, J. Am.
triphenylindene [272]. Chem. Soc. 1964, 88, 2669.
23. R. Dietz, B. E. Larcombe, J. Chem. Soc. B
1970, 1369.
References 24. H. Lund, O. Hammerich, (Eds.), Organic
Electrochemistry, Marcel Dekker, New York,
1. G. J. Hoijtink, Recl. Trav. Chim. Pays-Bas 2001.
1955, 74, 1525. 25. R. S. Nicolson, I. Shain, Anal. Chem. 1964,
2. M. E. Peover in Electroanalytical Chemistry 36, 706.
(Ed.: A. J. Bard), Marcel Dekker, New York, 26. R. N. Adams, Electrochemistry at Solid Elec-
1967, Vol. 2. trodes, Marcel Dekker, New York, 1969.
3. G. J. Hoijtink in Advances in Electrochem- 27. J. Heinze, Angew. Chem. 1984, 96, 823.
istry and Electrochemical Engineering (Ed.: 28. J. Heinze, Angew. Chem., Int. Ed. 1984, 23,
P. Delahay), Wiley-Interscience, New York, 831.
1970, Vol. 7. 29. H. Kiesele, Anal. Chem. 1981, 53, 1952.
4. M. E. Peover in Reactions of Molecules at 30. J. Heinze, J. Mortensen, K. Müllen et al., J.
Electrodes (Ed.: N. S. Hush), John Wiley, Electrochem. Soc. Chem. Commun. 1987, 701.
New York, 1971, pp. 259–281. 31. K. Meerholz, H. Gregorius, K. Müllen et al.,
5. M. Szwarc, J. Jagur-Grodzinski in Ions Adv. Mater. 1994, 6, 671.
and Ion Pairs in Organic Reactions (Ed.: 32. B. Schlicke, A.-D. Schlüter, P. Hauser et al.,
M. Szwarc), Wiley- Interscience, New York, Angew. Chem. 1997, 109, 2019.
1974, Vol. 2, Chap. 1. 33. B. Schlicke, A.-D. Schlüter, P. Hauser et al.,
6. N. L. Holy, Chem. Rev. 1974, 74, 243. Angew. Chem., Int. Ed. 1997, 36, 1996.
7. D. H. Evans, Acc. Chem. Res. 1977, 10, 313.
34. A. Demortier, A. J. Bard, J. Am. Chem. Soc.
8. O. Hammerich, V. D. Parker, Electrochim.
1973, 95, 3495.
Acta 1973, 18, 537.
35. K. Meerholz, J. Heinze, J. Am. Chem. Soc.
9. B. S. Jensen, V. D. Parker, J. Am. Chem. Soc.
1989, 111, 2325.
1975, 97, 5211.
36. A. J. Fry, Synthetic Organic Electrochemistry,
10. D. MacInnes Jr., M. A. Druy, P. J. Nigrey
Harper & Row, New York, 1972, Chap. 7.
et al., J. Chem. Soc. Chem. Commun. 1981,
317–319. 37. J. Mortensen, J. Heinze, Angew. Chem.
11. K. M. Kadish, R. S. Ruoff, (Eds.), Fullerenes, 1984, 96, 65.
The Electrochemical Society, Pennington, 38. J. Mortensen, J. Heinze, Angew. Chem., Int.
NJ, 1994. Ed. 1984, 23, 84.
12. J. Heinze, M. Störzbach, J. Mortensen, Ber. 39. D. H. Geske, A. Maki, J. Am. Chem. Soc.
Bunsen-Ges Phys. Chem. 1987, 91, 960. 1960, 82, 2671.
13. D. Dubois, K. M. Kadish, S. Flanagan et al., 40. R. E. Sioda, D. O. Cowan, W. S. Koski, J.
J. Am Chem. Soc. 1991, 113, 4364. Am. Chem. Soc. 1967, 89, 230.
14. Q. Xie, E. Perez-Cordero, L. Echegoyen, J. 41. R. D. Allendorfer, L. L. Miller, M. E.
Am. Chem. Soc. 1992, 114, 3978. Larscheid et al., J. Org. Chem. 1975, 40, 97.
15. G. J. Hoijtink, J. van Schooten, Recl. Trav. 42. I. Bergman, Trans. Faraday Soc. 1954, 50,
Chim. Pays-Bas 1952, 71, 1089. 829.
16. G. J. Hoijtink, J. van Schooten, Recl. Trav. 43. P. H. Given, J. Chem. Soc. 1958, 2684.
Chim. Pays-Bas 1953, 72, 691, 903. 44. M. J. S. Dewar, C. de Llano, J. Am. Chem.
17. G. J. Hoijtink, J. van Schooten, E. de Boer Soc. 1969, 91, 789.
et al., Recl. Trav. Chim. Pays-Bas 1954, 73, 45. A. J. Fry, L. L. Chung, V. Boekelheide,
355. Tetrahedron Lett. 1974, 5, 445.
46. A. J. Fry, C. S. Hutchins, L. L. Chung, J. 72. J. F. M. Oth, G. Schröder, J. Chem. Soc. B.

Am. Chem. Soc. 1975, 97, 591. 1971, 904.
47. J. Mortensen, J. Heinze, Tetrahedron Lett. 73. L. Anderson, M. J. Broadhurst, L. A. Paque-
1985, 26, 415. tte, J. Am. Chem. Soc. 1973, 95, 2198.
48. M. E. Peover, J. D. Davies, J. Electroanal. 74. F. M. Oth, K. Müllen, K. Königshofen et al.,
Chem. 1963, 6, 46. Helv. Chim. Acta 1974, 57, 2387.
49. J. O‘M. Bockris, A. K. N. Reddy, Modern 75. K. Müllen, W. Huber, T. Meul et al., J. Am.
Electrochemistry, Plenum Press, New York, Chem. Soc. 1982, 104, 5403.
1998. 76. K. Ankner, B. Lamm, B. Thulin et al., Acta
50. K. H. J. Buschow, J. Dieleman, G. J. Hoi- Chem. Scand. 1978, B32, 155.
jtink, J. Chem. Phys. 1965, 42, 1993. 77. W. Huber, K. Müllen, O. Wennerström,
51. D. N. Bhattacharyya, C. L. Lee, J. Smid et al., Angew. Chem., Int. Ed. 1980, 19, 624.
J. Phys. Chem. 1965, 69, 608. 78. W. Huber, K. Müllen, R. Busch et al.,
52. M. Szwarc, Acc. Chem. Res. 1972, 5, 169. Angew. Chem. 1982, 94, 294.
53. J. Mortensen, J. Heinze, H. Herbst et al., J. 79. W. Huber, K. Müllen, R. Busch et al.,
Electroanal. Chem. 1992, 324, 201. Angew. Chem., Int. Ed. Engl. 1982, 21, 301.
54. A. Rainis, R. Tung, M. Szwarc, J. Am. Chem. 80. K. Hafner, Angew. Chem., Int. Ed. Engl.
Soc. 1973, 95, 659. 1959, 70, 419.
55. L. A. Avaca, A. Bewick, J. Electroanal. Chem. 81. A. J. Fry in Topics in Organic Electrochemistry
1973, 41, 405. (Eds.: A. J. Fry, W. E. Britton), Plenum
56. R. D. Allendoerfer, P. H. Rieger, J. Am. Press, New York, 1986.
Chem. Soc. 1965, 87, 2336. 82. K. Müllen, J. F. M. Oth, H.-W. Engels et al.,
57. R. D. Allendoerfer, J. Am. Chem. Soc. 1975, Angew. Chem. 1979, 91, 251.
83. K. Müllen, J. F. M. Oth, H.-W. Engels et al.,
97, 218.
Angew. Chem., Int. Ed. Engl. 1979, 18, 229.
58. B. J. Huebert, D. E. Smith, J. Electroanal.
84. R. W. Johnson, J. Am. Chem. Soc. 1977, 99,
Chem. 1971, 31, 333.
1461.
59. R. D. Rieke, R. A. Copenhafer, J. Elec-
85. S. I. Zhdanov, Z. Phys. Chem. (Leipzig)
troanal. Chem. 1974, 56, 409.
Sonderheft, 1958, 235.
60. L. A. Paquette, G. D. Ewing, S. Traynor
86. P. H. Plesch, A. Stasko, J. Chem. Soc. B
et al., J. Am. Chem. Soc. 1977, 99, 6115.
1971, 2052.
61. L. A. Paquette, S. V. Levy, R. H. Meisinger 87. J. M. Lead, T. Teherane, A. J. Bard, J. Elec-
et al., J. Am. Chem. Soc. 1974, 96, 5806. troanal. Chem. 1978, 9, 275.
62. H. Lehmkuhl, S. Kintopf, E. Janssen, J. 88. R. Breslow, W. Bahary, W. Reinmuth, J.
Organomet. Chem. 1973, 56, 41. Am. Chem. Soc. 1961, 83, 1763.
63. W. H. Smith, A. J. Bard, J. Electroanal. 89. R. W. Johnson, T. Widlanski, R. Breslow,
Chem. 1977, 76, 19. Tetrahedron Lett. 1976, 4685.
64. A. J. Fry, J. Simon, T. Tashiro et al., Acta 90. R. Breslow, W. Chu, J. Am. Chem. Soc. 1973,
Chem. Scand. 1983, B37, 445. 95, 411.
65. L. A. Paquette, J. M. Photis, G. D. Ewing, J. 91. M. R. Wasielewski, R. Breslow, J. Am.
Am. Chem. Soc. 1975, 97, 3538. Chem. Soc. 1976, 98, 4222.
66. L. A. Paquette, M. A. Kesselmayer, G. E. 92. G. Kothe, W. Sümmermann, H. Baum-
Underiner et al., J. Am. Chem. Soc. 1992, gärtel et al., Tetrahedron Lett. 1969, 2185.
144, 2644. 93. H. Volz, W. Lotsch, Tetrahedron Lett. 1969,
67. J. F. M. Oth, H. Baumann, J.-M. Gilles et al., 2275.
J. Am. Chem. Soc. 1972, 94, 3498. 94. T. A. Skotheim, Handbook of Conducting
68. D. Tanner, O. Wennerström, E. Vogel, Polymers, Marcel Dekker, New York, 1986.
Tetrahedron Lett. 1982, 23, 1221. 95. T. A. Skotheim, Handbook of Conducting
69. J. F. M. Oth, E. P. Woo, F. Sondheimer, J. Polymers, 2nd ed., Marcel Dekker, New
Am. Chem. Soc. 1973, 95, 7337. York, 1998.
70. O. Reiser, B. König, K. Meerholz et al., J. 96. J. E. Frommer, R. R. Chance in Encyclope-
Am. Chem. Soc. 1993, 115, 3511. dia of Polymer Science and Engineering (Eds.:
71. A. Böhm, K. Meerholz, J. Heinze et al., J. M. Grayson, J. Kroschwitz), John Wiley,
Am. Chem. Soc. 1992, 114, 688. New York, 1986, p. 462 ff.
97. J. Heinze, Top. Curr. Chem. 1990, 152, 1. 124. W. E. Britton in Topics in Organic Chemistry
98. J. Mortensen, J. Heinze, J. Electroanal. (Eds.: A. J. Fry, W. E. Britton), Plenum
Chem. 1984, 175, 333. Press, New York, 1986, pp. 227–253.
99. K. Itaya, A. J. Bard, M. Szwarc, Z. Phys. 125. D. H. Evans, R. W. Busch, J. Am. Chem. Soc.
Chem. N. F. 1978, 112, 1. 1982, 104, 5057.
100. F. Gerson, J. Lopez, A. Metzger, Helv. 126. L. Echegoyen in Organic Electrochemistry
Chim. Acta 1980, 63, 2135. (Eds.: H. Lund, O. Hammerich), Marcel
101. L. A. Paquette, G. D. Ewing, S. Traynor, J. Dekker, New York, 2000, pp. 323–339.
Am. Chem. Soc. 1976, 98, 279. 127. K. Meerholz, P. Tschuncky, J. Heinze,
102. A. J. Fry, T. A. Powers, K. Müllen et al., J. Electroanal. Chem. 1993, 347, 425.
Tetrahedron Lett. 1985, 26, 5879. 128. J. Heinze, A. Smie in Fullerenes (Eds.:
103. A. F. Diaz, J. Crowley, J. Bargon et al., J. K. M. Kadish, R. S. Ruoff), The Elec-
Electroanal. Chem. 1981, 121, 355. trochemical Society, Pennington, NJ,
104. J. Heinze, P. Tschuncky in The Oligomer pp. 1117–1132.
Approach (Eds.: K. Müllen, G. Wegner), 129. K. F. Thier, M. Mehring, F. Rachdi, Phys.
Wiley-VCH, Weinheim, Germany, 1998, Rev. 1997, B55, 124.
pp. 479–514. 130. N. S. Hush, Trans. Faraday Soc. 1961, 57,
105. A. Bohnen, H. J. Räder, K. Müllen, Synth. 557.
Met. 1992, 42, 37. 131. R. A. Marcus, Can. J. Chem. 1959, 37, 155.
106. M. Baumgarten, K. Müllen, Top. Curr. 132. R. A. Marcus, Angew. Chem. 1993, 105,
Chem. 1992, 169, 1. 1161.
107. A. Ohlemacher, R. Schenk, H.-P. Weitzel 133. R. A. Marcus, Angew. Chem., Int. Ed. Engl.
et al., Macromol. Chem. 1992, 193, 81. 1993, 32, 1111.
108. H. P. Weitzel, A. Bohnen, K. Müllen, 134. R. R. Dogonadze, A. M. Kuznetsov, A. A.
Makromol. Chem. 1990, 191, 2815. Chernenko, Russ. Chem. Rev. 1965, 34, 759.
109. A. Bohnen, W. Heitz, K. Müllen et al., 135. L. Eberson, Adv. Phys. Org. Chem. 1982,
Makromol. Chem. 1991, 192, 1679. 18, 7.
110. H. Naarmann, N. Theophilou, Synth. Met. 136. F. A. L. Anet, J. Am. Chem. Soc. 1962, 84,
1987, 22, 1. 671.
111. A. Kiehl, A. Eberhardt, M. Adam et al., 137. J. M. Hale in Reactions of Molecules at
Angew. Chem. 1992, 104, 1623. Electrodes (Ed.: N. S. Hush), John Wiley,
112. A. Kiehl, A. Eberhardt, M. Adam et al., New York, 1971, pp. 229–257.
Angew. Chem., Int. Ed. 1992, 31, 1588. 138. B. S. Jensen, A. Ronlan, V. D. Parker, Acta
113. T. Bally, K. Roth, W. Tang et al., J. Am. Chem. Scand. 1975, B29, 394.
Chem. Soc. 1992, 114, 2440. 139. B. Großmann, J. Heinze, G. Grampp, un-
114. K. Knoll, R. Schrock, J. Am. Chem. Soc. published results.
1989, 111, 7989. 140. B. Brielbeck, J. C. Rühl, D. H. Evans, J. Am.
115. E. Ehrenfreud, D. Moses, A. J. Heeger et al., Chem. Soc. 1993, 115, 11898.
Chem. Phys. Lett. 1992, 196, 84. 141. D. H. Evans, K. O‘Connell in Electroana-
116. A. Jeevarajan, M. Khaled, L. D. Kispert, J. lytical Chemistry, (Ed.: A. J. Bard), Marcel
Phys. Chem. 1994, 98, 7777. Dekker, New York, 1986, pp. 113–207,
117. L. M. Tolbert, Acc. Chem. Res. 1992, 25, 561. Vol. 14.
118. G. Broszeit, F. Diepenbrock, O. Gräf et al., 142. R. A. Marcus, J. Phys. Chem. 1963, 67, 853.
Liebigs Ann. Chem. 1997, 2205. 143. L. S. Marcoux, R. N. Adams, S. W. Feldberg,
119. J. Heinze, P. Tschuncky, A. Smie, J. Solid J. Phys. Chem. 1969, 73, 2611.
State Electrochem. 1998, 2, 102. 144. J. Heinze, M. Dietrich, K. Hinkelmann
120. B. S. Jensen, R. Lines, P. Pagsberg et al., et al., DECHEMA-Monographie 1989, 112,
Acta Chem. Scand. 1977, B31, 707. 61.
121. M. Grezesczuk, D. E. Smith, J. Electroanal. 145. J. Simonet, M.-A. Michel, H. Lund, Acta
Chem. 1984, 162, 189. Chem. Scand. 1975, B29, 489.
122. T. Troll, M. M. Baizer, Electrochim. Acta. 146. E. Hobolth, H. Lund, Acta Chem. Scand.
1974, 19, 951. 1977, B31, 395.
123. G. Farnia, F. Maran, G. Sandonà, J. Chem. 147. T. Lund, H. Lund, Acta Chem. Scand. 1986,
Soc. Faraday Trans. I 1986, 82, 1885. B40, 470.
148. T. Lund, H. Lund, Acta Chem. Scand. 1987, 173. G. J. Hoijtink, Recl. Trav. Chim. Pays-Bas
B41, 93. 1954, 73, 895.
149. K. Daasbjerg, S. U. Pedersen, H. Lund, Acta 174. G. J. Hoijtink, Recl. Trav. Chim. Pays-Bas
Chem. Scand. 1989, B43, 876. 1957, 76, 885.
150. S. U. Pedersen, T. Lund, Acta Chem. Scand. 175. S. Valcher, A. M. Ghe, J. Electroanal. Chem.
1991, B45, 397. 1974, 55, 407.
151. C. P. Andrieux, C. Blocman, J. M. Dumas- 176. B. Aalstadt, V. D. Parker, J. Electroanal.
Bouchiat et al., J. Am. Chem. Soc. 1979, 101, Chem. 1981, 121, 73.
3806. 177. E. Ahlberg, V. D. Parker, Acta Chem. Scand.
152. C. P. Andrieux, J. M. Dumas-Bouchiat, J. M. 1981, B35, 117.
Savéant, J. Electroanal. Chem. 1978, 87, 39. 178. V. D. Parker, Acta Chem. Scand. 1981, B35,
153. C. P. Andrieux, J. M. Dumas-Bouchiat, J. M. 349.
Savéant, J. Electroanal. Chem. 1978, 87, 55. 179. V. D. Parker, Acta Chem. Scand. 1981, B35,
154. C. P. Andrieux, J. M. Dumas-Bouchiat, J. M. 373.
Savéant, J. Electroanal. Chem. 1978, 88, 43. 180. C. Amatore, M. Gareil, J. M. Savéant, J.
155. C. P. Andrieux, J. M. Dumas-Bouchiat, Electroanal. Chem. 1984, 176, 377.
J. M. Savéant, J. Electroanal. Chem. 1980, 181. M. F. Nielsen, O. Hammerich, V. D. Parker,
113, 1. Acta Chem. Scand. 1986, B40, 101.
156. C. P. Andrieux, J. M. Dumas-Bouchiat, 182. M. F. Nielsen, O. Hammerich, V. D. Parker,
F. M‘Halla et al., J. Electroanal. Chem. 1980, Acta Chem. Scand. 1987, B41, 64.
113, 19. 183. C. Amatore, J. M. Savéant, J. Electroanal.
157. C. P. Andrieux, C. Blocman, J. M. Dumas- Chem. 1980, 107, 353.
Bouchiat et al., J. Am. Chem. Soc. 1979, 101, 184. I. Bergman, Trans. Faraday Soc. 1952, 52,
3431. 690.
158. C. Amatore, M. Gareil, J. M. Savéant, 185. A. J. Fry, A. Schuettenberg, J. Org. Chem.
J. Electroanal. Chem. 1983, 147, 1. 1974, 39, 2452.
159. R. A. Marcus, J. Chem. Phys. 1965, 43, 2654. 186. L. Eberson, Z. Blum, B. Helge et al., Tetra-
160. R. A. Marcus, Electrochim. Acta. 1968, 13, hedron 1978, 34, 731.
1217. 187. I. Bergman, Polarography 1964, MacMillan,
161. L. R. Faulkner, A. J. Bard in Electroanalyt- London, 1966, pp. 925–947.
ical Chemistry (Ed.: A. J. Bard), Marcel 188. A. Streitwieser, S. Suzuki, Tetrahedron 1961,
Dekker, New York, 1977, pp. 1–95, Vol. 10. 16, 153.
162. G. J. Hoijtink, Discuss. Faraday Soc. 1968, 189. E. Heilbronner, H. Bock, Das HMO-Modell
45, 14. und seine Anwendung, Verlag Chemie,
163. H. Tachikawa, A. J. Bard, Chem. Phys. Lett. Weinheim, Germany, 1968.
1974, 26, 568. 190. G. J. Hoijtink, Recl. Trav. Chim. Pays-Bas
164. E. A. Chandross, J. W. Longworth, R. E. 1961, 76, 775.
Visco, J. Am. Chem. Soc. 1965, 87, 3259. 191. P. E. Hansen, O. Blaabjerg, A. Berg, Acta
165. A. Weller, K. Zachariasse, Chem. Phys. Lett. Chem. Scand. 1978, B32, 720.
1971, 10, 590. 192. A. Misono, T. Osa, T. Yamagishi, Bull.
166. S. M. Park, A. J. Bard, J. Am. Chem. Soc. Chem. Soc. Jpn. 1968, 41, 2921.
1975, 97, 2978. 193. C. Amatore, G. Capobianco, G. Farnia et al.,
167. S. M. Park, M. T. Paffett, G. H. Daub, J. Am. Chem. Soc. 1985, 107, 1815.
J. Am. Chem. Soc. 1977, 99, 5393. 194. G. Farnia, G. Sandonà, F. Marcuzzi et al.,
168. T. M. Siegel, H. B. Mark, J. Am. Chem. Soc. J. Chem. Soc. Perkin Trans. 1988, 2,
1977, 99, 5393. 247.
169. D. L. Atkins, R. L. Birke, Chem. Phys. Lett. 195. A. Lagu, H. B. Mark Jr., J. R. Jezorek, J. Org.
1974, 29, 428. Chem. 1977, 42, 1063.
170. T. D. Santa-Cruz, D. L. Atkins, R. L. Birke, 196. K. J. Borhani, M. D. Hawley, J. Electroanal.
J. Am. Chem. Soc. 1976, 98, 1677. Chem. 1979, 101, 407.
171. G. H. Brilmyer, A. J. Bard, J. Electrochem. 197. A. D. Moro, G. Farnia, F. Marcuzzi et al.,
Soc. 1980, 127, 104. Nouv. J. Chim. 1980, 4, 3.
172. A. J. Birch, R. G. Subba, Adv. Org. Chem. 198. G. Capobianco, G. Farnia, G. Sandonà et al.,
1972, 8, 1. J. Electroanal. Chem. 1982, 134, 363.
199. F. Beck, H. Gerischer, Ber. Bunsen-Ges. 230. C. Amatore, J. Pinson, J. M. Savéant, J.

Phys. Chem. 1961, 65, 504. Electroanal. Chem. 1982, 137, 143.
200. S. Pons, S. B. Khoo, J. Am. Chem. Soc. 1982, 231. C. Amatore, J. Pinson, J. M. Savéant, J.
104, 3845. Electroanal. Chem. 1982, 139, 193.
201. D. J. Morantz, E. Warhurst, Trans. Faraday 232. J. M. Savéant, Acta Chem. Scand. 1983, B37,
Soc. 1955, 51, 1375. 365.
202. J. F. Garst, Acc. Chem. Res. 1971, 4, 400. 233. C. Amatore, D. Garreau, M. Hammi et al.,
203. H. Lund, M.-A. Michel, J. Simonet, Acta J. Electroanal. Chem. 1985, 184, 1.
Chem. Scand. 1974, B28, 900. 234. P. Debye, Trans. Electrochem. Soc. 1942, 82,
204. P. Martigny, J. Simonet, J. Electroanal. 265.
Chem. 1979, 101, 275. 235. J. Heinze in Microelectrodes: Theory and
205. A. Pross, S. S. Shaik, Acc. Chem. Res. 1983, Applications (Eds.: I. Montenegro, M. A.
16, 363. Queiros, J. L. Daschbach), NATO ASI Se-
206. A. Pross, Acc. Chem. Res. 1985, 18, 212. ries, Kluwer Academic Publishers, Dor-
207. E. Hebert, J.-P. Mazaleyrat, Z. Welvart et al., drecht, 1991, pp. 283–294, Vol. 197.
Nouv. J. Chim. 1985, 9, 75. 236. R. Eliason, O. Hammerich, V. D. Parker,
208. S. U. Pedersen, T. Lund, K. Daasbjerg et al., Acta Chem. Scand. 1988, 42, 7.
Acta Chem. Scand. 1998, 52, 657. 237. O. Hammerich, M. F. Nielsen, Acta Chem.
209. H. S. Sørensen, K. Daasbjerg, Acta Chem. Scand. 1998, 52, 831.
Scand. 1998, 52, 51. 238. F. Beck, Angew. Chem. 1972, 84, 798.
210. H. Lund, Acta Chem. Scand. 1977, B31, 424. 239. F. Beck, Angew. Chem., Int. Ed. Engl. 1972,
211. R. Engels, H. J. Schäfer, Angew. Chem., Int. 11, 760.
Ed. Engl. 1978, 17, 460. 240. M. M. Baizer, J. P. Petrovich in Progress in
212. R. Engels, Dissertation Univ. Münster, Physical Organic Chemistry (Eds.: A. Streit-
1978. wieser, R. W. Taft), Wiley-Interscience, New
213. B. Brauer, Dissertation Univ. Münster, York, 1970, pp. 189–227, Vol. 7.
1982. 241. F. Zhou, A. J. Bard, J. Am. Chem. Soc. 1994,
214. S. Wawzonek, D. Wearring, J. Am. Chem. 116, 393.
Soc. 1959, 81, 2067. 242. W. Schlenk, J. Appenrodt, A. Michael et al.,
215. J. W. Loveland, U. S. Pat. 3,214,356 1965. Ber. Dtsch. Chem. Ges. 1914, 47, 473.
216. J. W. Loveland, Chem. Abstr. 1966, 64, 671d. 243. K. Ziegler, K. Bähr, Ber. Dtsch. Chem. Ges.
217. J. W. Loveland, U. S. Pat. 3,032,489 1962. 1928, 61, 253.
218. J. W. Loveland, Chem. Abstr. 1962, 57, 4470. 244. M. Szwarc, Ber. Bunsen-Ges. Phys. Chem.
219. W. C. Niekam, U. S. Pat. 3,334,045 1967. 1963, 67, 763.
220. W. C. Niekam, Chem. Abstr. 1968, 68, 8809. 245. M. Szwarc, Carbanions, Living Polymers and
221. R. Dietz, M. E. Peover, Discuss. Faraday Soc. Electron Transfer Processes, Wiley, New York,
1968, 45, 167. 1968.
222. H. Lund, J. Simonet, J. Electroanal. Chem. 246. M. Szwarc, in Progress in Physical Or-
1975, 65, 205. ganic Chemistry, (Eds.: A. Streitwieser,
223. D. A. Tyssee, J. H. Wagenknecht, M. M. R. W. Taft), Wiley-Interscience, New York,
Baizer et al., Tetrahedron Lett. 1972, 4809. 1968, pp. 323–438, Vol. 6.
224. A. J. L. Beckwith, R. O. C. Norman, J. Chem. 247. N. Yamazaki, S. Nakahama, S. Kambara, J.
Soc. B 1969, 400. Polym. Sci., Part B 1965, 3, 57.
225. M. M. Baizer, J. D. Anderson, J. Org. Chem. 248. B. L. Funt, S. W. Laurent, Can. J. Chem.
1965, 30, 1348. 1964, 42, 2728.
226. L. D. McKeever, R. Waack, J. Organomet. 249. B. L. Funt, S. N. Bhadani, Can. J. Chem.
Chem. 1969, 17, 142. 1964, 42, 2733.
227. H. C. Wang, E. D. Lillie, S. Slomkowski 250. B. L. Funt, D. Richardson, S. N. Bhadani,
et al., J. Am. Chem. Soc. 1977, 99, 4612. Can. J. Chem. 1966, 44, 711.
228. A. Yildiz, H. Baumgärtel, Ber. Bunsen-Ges. 251. J. D. Anderson, J. Polym. Sci., Part A-1 1968,
Phys. Chem. 1977, 81, 1177. 6, 3185.
229. O. Hammerich, V. D. Parker, Acta Chem. 252. B. L. Funt, S. N. Bhadani, D. Richardson, J.
Scand. 1981, B35, 381. Polym. Sci., Part A-1 1966, 4, 2871.
253. E. Laviron, Y. Mugnier, J. Electroanal. Chem. 263. N. L. Bauld, J. Cessac, F. R. Farr et al., J.
1978, 93, 69. Am. Chem. Soc. 1976, 98, 4561.
254. P. Netta, H. Levanon, J. Phys. Chem. 1977, 264. R. Schenk, H. Gregorius, K. Meerholz et al.,
81, 2288. J. Am. Chem. Soc. 1991, 113, 2634.
255. A. J. Bard, J. Phelps, J. Electroanal. Chem. 265. M. Horner, S. Hünig, J. Am. Chem. Soc.
1970, 25, App. 2. 1977, 99, 6120.
256. B. L. Funt, D. Gray, J. Electrochem. Soc. 266. K. Müllen, W. Huber, Helv. Chim. Acta
1970, 117, 1020. 1978, 61, 1310.
257. J. F. Garst, J. G. Pacifici, E. R. Zabolotny, J. 267. L. L. Miller, E. A. Mayeda, J. Am. Chem. Soc.
Am. Chem. Soc. 1966, 88, 3872. 1970, 92, 5818.
258. K. Ziegler, F. Thielmann, Chem. Ber. 1923, 268. L. L. Miller, R. F. Boyer, J. Am. Chem. Soc.
56, 1740. 1971, 93, 650.
259. A. Lagendijk, M. Szwarc, J. Am. Chem. Soc. 269. L. L. McCullough, Acc. Chem. Res. 1980, 13,
1971, 93, 5359. 270.
260. O. Hammerich, J. M. Savéant, J. Chem. 270. L. L. Miller, R. F. Boyer, J. Am. Chem. Soc.
Soc., Chem. Commun. 1979, 938. 1971, 93, 646.
261. D. Casson, B. J. Tabner, J. Chem. Soc. B 271. G. Farnia, F. Marcuzzi, G. Melloni et al., J.
1969, 887. Am. Chem. Soc. 1989, 111, 918.
262. R. B. Woodward, R. Hoffmann, The Conser- 272. H. Kiesele, Angew. Chem., Int. Ed. Engl.
vation of Orbital Symmetry, Verlag Chemie, 1983, 22, 254.
Weinheim, Germany, 1970.
125
5
Anodic Reactions of Alkanes,
Alkenes, and Aromatic
Compounds
..
Hans J. Sch afer
.. .. ..
Organisch-Chemisches Institut der Universit at M unster, M unster, FRG
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
5.2 Anodic Oxidation of Alkanes . . . . . . . . . . . . . . . . . . . . . . . . . . . 128

5.2.1 Anodic Substitution of CH Bonds . . . . . . . . . . . . . . . . . . . . . . . . 128
5.2.2 Oxidation of Remote CH Bonds in Ketones, Carboxylic Acids, and
Steroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
5.2.3 C,C Bond Cleavage in Hydrocarbons . . . . . . . . . . . . . . . . . . . . . . 132
5.2.4 Oxidation of Hydrocarbons in Fuel Cells . . . . . . . . . . . . . . . . . . . 133
5.3 Anodic Oxidation of Alkenes . . . . . . . . . . . . . . . . . . . . . . . . . . . 134

5.3.1 General Reaction Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
5.3.2 Anodic Coupling of Alkenes by Way of Radical Cations . . . . . . . . . 134
5.3.2.1 Intermolecular Coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
5.3.2.2 Intramolecular Coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
5.3.3 Anodic Substitution and Addition via Radical Cations . . . . . . . . . . 138
5.3.4 Addition via Oxidation of Nucleophiles to Radicals . . . . . . . . . . . . 140
5.3.5 Mediated Oxidation of Alkenes . . . . . . . . . . . . . . . . . . . . . . . . . . 145
5.3.6 Anodically Induced Cycloadditions . . . . . . . . . . . . . . . . . . . . . . . 146
5.4 Anodic Oxidation of Aromatic Compounds . . . . . . . . . . . . . . . . . 149

5.4.1 General Principles of Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . 149
5.4.2 Anodic Coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
5.4.2.1 Nuclear Aromatic Substitution . . . . . . . . . . . . . . . . . . . . . . . . . . 155
5.4.2.2 Anodic Side Chain Substitution of Aromatic Compounds . . . . . . . . 159
5.4.3 Anodic Addition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
126 5 Anodic Reactions of Alkanes, Alkenes, and Aromatic Compounds
5.5 Comparison of Anodic Conversions of Alkanes, Alkenes, and Aromatic

Compounds with their Chemical Transformations . . . . . . . . . . . . 161
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
127
5.1 and involve radical cations, radicals, and

Introduction cations. At the anode, these intermediates
are generated in the following way (Eq. 1):
This chapter deals with anodic oxidation of
saturated hydrocarbons, olefins, and aro- −e
RH+
•
matic compounds. Substituted hydrocar- (a) RH
bons are included, when the substituents −H+ −e
strongly influence the reactivity. Anodic (b) RH R− R•
functional group interconversions (FGI) of −e
(c) R• R+
the substituents are covered in Chapters 6,
8–10 and 15. (1)
Transfer of an electron from a σ - or
The principal reactions encountered in
π-bond leads to a radical cation (Eq. 1a),
anodic reactions of hydrocarbons involve
oxidation with a preceding (Eq. 1b) or
1. substitution of a hydrogen atom in a a succeeding deprotonation generates a
C−H bond for a heteroatom, radical, and oxidation of the radical forms
2. addition of carbon or heteroatoms to a a cation (Eq. 1c). The radical cations can
C,C double bond, react according to Scheme 1 [1, 2].
3. coupling of alkenes or aromatic com- Radical cations can dimerize in a radi-
pounds, cal–radical coupling reaction (Scheme 1a)
4. dehydrogenation, to afford dimer dications. An alternative
5. C,C bond cleavage and pathway to form the dimer dication is a rad-
6. rearrangement. ical–substrate coupling in an electrophilic
addition of the radical cation to the nu-
Mechanistically, there are several pathways cleophilic substrate. The dimer dication
leading to the products. Such mechanisms can lose two protons to form a bis-dehydro
are, however, only in a limited number dimer or react with two nucleophiles to
of cases, clearly established and can yield a disubstituted dimer.
furthermore change depending on the The radical cation can alternatively
reaction conditions. react with a heteroatom nucleophile
The pathways consist mostly of suc- (Scheme 1b) and after deprotonation lead
cessive reactions being chemical- and to a radical bound to the nucleophile.
electron-transfer steps (C and E steps) This radical can be further oxidized to
−2H+
R R
+
RH•
+HR RH+
2NuH
RH+• −e NuHR RHNu
−2H+
RH
(a) +RH RH•
−H+
RNu
NuH • −e +
RH+• RHNu RHNu
−H+
NuH
RHNu2
(b) −H+
Scheme 1 Reactions of radical cations (a) C,C-bond formation, (b) substitution and addition.
a cation, that is, deprotonated to a sub- 5.2

stituted alkene or reacts with a second Anodic Oxidation of Alkanes
nucleophile to an addition product. The
5.2.1
cationic intermediates can also rearrange
Anodic Substitution of CH Bonds
in this sequence.
The radicals undergo the usual re-
The nonactivated CH bond in aliphatic
actions as dimerizations, disproportion-
hydrocarbons is oxidized at a potential that
ations, atom-transfer reactions, or ad-
lies mostly more anodic than 2.5 V [vs. SCE
ditions [3]. Compared to homogeneous (saturated calomel electrode)] [5, 6]. This
radical reactions, bimolecular dimeriza- necessitates electrolytes with high anodic
tions and disproportionations are favored decomposition potentials.
at the electrode. Stationary radical con- In fluorosulfonic acid the anodic oxi-
centrations are higher in heterogeneous dation of cyclohexane in the presence of
electrochemical conversions because the different acids (RCO2 H) leads to a single
radicals are confined to a narrow reaction product with a rearranged carbon skele-
layer at the electrode surface. This layer ton, a 1-acyl-2-methyl-1-cyclopentene (1)
arises from the slow diffusion of the radi- in 50 to 60% yield (Eq. 2) [7, 8]. Also other
cals generated in high concentration at the alkanes have been converted at a smooth
electrode surface into the bulk of the solu- platinum anode into the corresponding
tion and their fast reaction on this way. The α,β-unsaturated ketones in 42 to 71% yield
more reactive the radical is, the narrower (Table 1) [8, 9]. Product formation is pro-
the reaction layer will be and thus the posed to occur by oxidation of the hydrocar-
higher is the concentration of the radical. bon to a carbocation (Eq. 1 and Scheme 1)
Carbocations also react as usual by that rearranges and gets deprotonated to
solvolysis, deprotonation, and rearrange- an alkene, which subsequently reacts with
ment [4]. an acylium cation from the carboxylic acid
These general reactions will be illus- to afford the α,β-unsaturated ketone (1)
trated by representative examples from the (Eq. 2) [8–10]. In the absence of acetic acid,
aforementioned groups of hydrocarbons. for example, in fluorosulfonic acid/sodium
5.2 Anodic Oxidation of Alkanes 129
Tab. 1 Anodic oxidation of alkanes in fluorosulfonic acid, 1.1 M acetic acid
Alkane Product Current yield [%]
(CH3 )3 CH (CH3 )2 C=CHCOCH3 64

n-C5 H12 C2 H5 (CH3 )C=CHCOCH3 40
C5 H9 COCH3 18
n-C6 H14 C6 H11 COCH3 51
n-C7 H16 C7 H13 COCH3 56
Cyclohexane 2-Methyl-1-acetyl-1-cyclopentene 71
Cyclooctane C8 H13 COCH3 42
fluorosulfonate, only oligomeric products through oxidation of the CH bond by

are isolated even at −20◦ [8]. The carbe- higher-valent nickel fluorides. Partial fluo-
nium ions formed can also be trapped by rination can be achieved by electrolysis in
carbon monoxide under pressure to yield molten KF · 2HF in the Phillips process at
highly selective carboxylic acids with cyclic porous carbon electrodes [12–15].
hydrocarbons but less selective with acyclic In trifluoroacetic acid [0.4 M TBABF4
ones [11]. (tetrabutyl ammonium tetrafluoroborate)]
unbranched alkanes are oxidized in fair
−2e + rearrange- to good yields to the corresponding triflu-
−H+ ment oroacetates (Table 2) [16]. As mechanism,
a 2e-oxidation and deprotonation to an
CH3 CH3 intermediate carbenium ion, that under-
+ −H+ RCO+ goes solvolysis is proposed. The isomer
distribution points to a fairly unselective
CH oxidation at the methylene groups.
CH3 CH3 Branched hydrocarbons are preferentially
+
COR −H+ COR oxidized at the tertiary CH bond [17].
Dichloromethane/trifluoroacetic acid
appears to be the solvent mixture of choice
(1) (50−60%)
for these substitutions. Dichloromethane
R: CH3, C2H5, C5H11 dissolves sufficiently the hydrocarbon
(2) and can be easily removed by distilla-
Electrochemical fluorination in anhy- tion. Trifluoroacetic acid is a nucleophile
drous hydrogen fluoride (Simons process) with a fairly high resistance towards
involves electrolysis of organic compounds oxidation. Platinum is the only suit-
(aliphatic hydrocarbons, haloalkanes, acid able anode material, while gold, glassy
halides, esters, ethers, amines) at nickel carbon, graphite, and lead dioxide cor-
electrodes. It leads mostly to perfluori- rode heavily. Electrolysis of cyclohex-
nated compounds, but is accompanied ane (2) in CH2 Cl2 /20% CF3 CO2 H/4%
to a high extent by cleavage and re- (CF3 CO)2 O/0.05 M TBABF4 at 0 ◦ C in
arrangement reactions. The mechanism an undivided cell at controlled cur-
of the formation of carbocations accord- rent afforded 92% cyclohexyl trifluoroac-
ing to Eq. (1) and Scheme 1 is assumed etate (3) (Eq. 3). While cyclohexane and
Tab. 2 Yields and isomer distribution of trifluoroacetates in the oxidation of

alkanes in CF3 CO2 H/0.4 M TBABF4
Alkane Current yield [%] Isomer distribution [%]

2-isomer 3-isomer 4-isomer
n-Octane 75 33 33 33
n-Heptane 75 45 45 10
n-Hexane 60 Not resolved
n-Pentane 50 Not resolved
cyclopentane (84%) lead to high yields Cl

−e, CH2Cl2/
of the cycloalkyl trifluoroacetates, those
of medium-sized rings are low (8-ring: CF3CO2H
Cl
30%, 10-ring: 6%, 12-ring: 9%) within (6)
a complex product mixture. The elec-
trolysis of norbornane (4) (Eq. 4) leads CF3CO2 Cl CF3CO2 Cl
in dichloromethane/trifluoroacetic acid to +
83% exo-2-norbornanol (5) after hydrolysis Cl Cl
of the trifluoroacetate [16]. The stereo- (7a) (7b)
chemistry of (5) indicates that possibly a
(5)
nonclassical norbornyl cation is involved. Trans-decalin tends to form oligomers as
Oxidation of trans-1,2-dichlorocyclohexane major products in CH2 Cl2 /CF3 CO2 H. In
(6) produces in CH2 Cl2 /20% CF3 CO2 H, the less acidic solvent, CH2 Cl2 /HOAc with
0.05 M TBABF4 at 0 ◦ C (7a,b) as main Bu4 NPF6 , the oligomerization can be sup-
product in 49% yield (Eq. 5) [16]. The in- pressed and 67% decalyl acetates together
ductive effect of the two chlorine atoms with 10% fluorodecalins are formed.
directs the oxidation mainly to C(4) and The chemoselectivity of the acetoxyla-
C(5). Thus the reaction provides a syn- tion is for C(4a) : C(1) : C(2) = 12 : 1 : 1.
thetically useful route from olefins to With Bu4 NOAc as supporting electrolyte,
homoallylic alcohols via protection of the 77% decalyl acetate is obtained in equal
double bond, anodic oxidation, hydrolysis, chemoselectivity but without fluorination
and deprotection. products. However, 35 to 40 F Mol−1 are
required in this case for complete conver-
O2CCF3 sion [18, 19].
The CH bonds of steroids sur-
−e
(3) prisingly can be oxidized even in
CH2Cl2/CF3CO2H methanol as a solvent. The electrol-
(2) (3) ysis of androstane in 0.1 M NaClO4
methanol/dichloromethane at a glassy car-
1. −e, CH2Cl2/ bon anode produces after 53% conver-
CF3CO2H sion 14% 6-methoxyandrostane and 27%
(4)
2. 2N NaOH OH 6-(methoxymethoxy) androstane [18, 19].
(4) (5) This remarkable regioselectivity is possibly
Tab. 3 Yields and isomer distribution of acetamidoalkanes obtained by

cpe of alkanes at a Pt-anode in CH3 CN/0.1 M TBABF4
Alkane Yield [%] Isomer distribution [%]

2-isomer 3-isomer 4-isomer
n-Octane 45 33 35 32
n-Heptane 48 45 45 10
n-Hexane 45 55 45
n-Pentane 50 Not resolved
due to the stacking of steroid molecules at and 1-hydroxymethyladamantane are of in-

the electrode surface. terest because they mimic the results in
Controlled potential electrolysis (cpe) mass spectrometry. Comparison of the ox-
of alkanes in acetonitrile/0.1 M TBABF4 idation of substituted adamantanes with
yields acetamidoalkanes (Table 3). Voltam- lead (IV), cobalt (III) and manganese (III)
metry and coulometry indicate a 2e- trifluoroacetates and with anodic oxida-
oxidation to a carbenium ion that tion in acetonitrile or trifluoroacetic acid,
subsequently reacts with the nitrogen shows that the anodic oxidation proceeds
atom of acetonitrile in a Ritter reaction via a radical cation intermediate, while
(Eq. 6) [20]. the metal salts form products by CH ab-
straction [22]. As a preparative result, the
−e −H+ anodic oxidation yields mainly fragmen-
RH RH+ • tation products, while with metal salts,
−e
+
hydrogen substitution is achieved prefer-
CH3C N
R+ RN CCH3 entially.
H2 O
RNHCOCH3 5.2.2
−H+ Oxidation of Remote CH Bonds in Ketones,
(6) Carboxylic Acids, and Steroids
The oxidation of substituted adaman-
tanes has been studied in detail by Ketones that lack α-branching are oxidized
Miller [21, 22] and Mellor [23–25]. Cpe in in acetonitrile/0.1 N LiClO4 at a platinum
a divided cell produces two types of prod- anode to afford acetamido ketones with
ucts by substitution at the tertiary carbon the acetamido group in remote position
atom: substitution of hydrogen for acet- (Table 4) [26, 27]. The products can be
amide with retention of the substituent X rationalized via oxidation of the carbonyl
in the adamantane molecule [substituent group to a radical cation. This initiates a
X (yield in %): H (90), Cl (91), F (65), γ -hydrogen abstraction that is analogous
CH3 (91), CO2 CH3 (64), CN (41)] and to this, found in mass spectrometry and
substitution of X for acetamide [Br (89), photochemistry. The formed radical is
CH2 OH (37), COCH3 (44), OH (41), OCH3 oxidized to a carbenium ion which possibly
(58)] [22]. Cleavages of 1-acetyl-, 1-bromo rearranges and undergoes a Ritter reaction
Tab. 4 Remote oxidation of ketones in acetonitrile/lithium perchlorate
Ketone Product [% yield]
2-Hexanone 5-Acetamido-2-hexanone (40)

2-Heptanone 6-Acetamido-2-heptanone (30)
2-Octanone 7-Acetamido-2-octanone (21)
6-Acetamido-2-octanone (30)
5-Acetamido-2-octanone (7)
4-Heptanone 2-Acetamido-4-heptanone (31)
2-Methyl-4-pentanone 2-Acetamido-2-methyl-4-pentanone (20)
4-Acetamido-2-hexanone (20)
2,6-Dimethyl-4-heptanone 2-Acetamido-2,6-dimethyl-4-heptanone (20)
6-Acetamido-2-methyl-4-octanone (20)
2,5-Dimethyl-3-hexanone 5-Acetamido-2-methyl-3-heptanone (25)
5-Acetamido-2,5-dimethyl-3-hexanone (35)
4,4-Dimethyl-2-pentanone 4-Acetamido-4-methyl-2-hexanone (50)
with acetonitrile (Eq. 7). 5.2.3

C,C Bond Cleavage in Hydrocarbons
−e
RCOCH2CH(CH3)2
By analogy with their behavior in mass
• H + +
O CH2 HO CH2 spectrometry, branched hydrocarbons are
−e
cleaved when oxidized in CH3 CN/TEABF4
R C CH R C CH
+
CH2 CH3 CH2 CH3 at −45 ◦ C. The resulting acetamides of
the fragments (Table 6) are formed by
O CH2CH3 cleavage of the initial radical cation at
CH3CN
H2O R C CH the C,C bond between the secondary
−2 H+ CH2 NHCOCH3 and tertiary C atom, to afford after a
(7) second electron transfer, carbocations,
In CH2 Cl2 /CF3 CCO2 H dodeca- and which react in a Ritter reaction with
tetradecanoic acid are preferentially tri- acetonitrile [29].
fluoroacetoxylated at the (ω-2) to (ω-4) Anodic oxidation of alkyl substi-
positions in 40 to 15% yield; no or only tuted cyclopropanes and spiroalkanes
very minor attack is found at C-2 to C- in methanol/TEATos (tetraethyl ammo-
6 [18]. The remarkable regioselectivity is nium tosylate) affords monomethoxy and
assumed to be due to the inductive ef- dimethoxy products in yields ranging
fect of the carboxylic group, which can from 6 to 86% [30, 31]. The products
be protonated in the more acidic region result from the cleavage of the most
close to the anode surface. Esters with an highly substituted C,C bond. In contrast
acyclic alkyl chain have been oxidized by to the anodic cleavage the acid-catalyzed
cpe in a divided cell in CH3 CN/LiClO4 cleavage occurs selectively at the less
or TEABF4 at a platinum anode with substituted carbon. The cleavage of hetero-
a high selectivity for the (ω-1)-position substituted cyclopropanes is reported in
(Table 5) [28]. Ref. [32–35].
Tab. 5 Remote oxidation of esters in acetonitrile/LiClO4 or TEABF4
Ester Acetamido ester [% yield]
Ethyl butanoate Ethyl 3-acetamidobutanoate (70)

Methyl hexanoate Methyl 5-acetamidohexanoate (42)
Methyl 4-acetamidohexanoate (11)
Methyl nonanoate Methyl 8-acetamidononanoate (25)
Methyl 3-methylbutanoate Methyl 3-acetamido-3-methylbutanoate (68)
Methyl 2-methylpropanoate Methyl 2-acetamido-2-methylpropanoate (58)
Methyl 3-acetamidobutanoate (4)
Tab. 6 Anodic oxidation of branched hydrocarbons in acetonitrile/TEABF4
Hydrocarbon Products
2,3-Dimethylbutane 2-Propylacetamide
2,2,4-Trimethylpentane t-Butylacetamide, 2-propylacetamide, 2-butylacetamide
2,2-Dimethylbutane t-Butylacetamide, t-pentylacetamide, isopentylacetamide
t-Butylcyclohexane t-Butylacetamide, cyclohexylacetamide
n-Octane 2-Octylacetamide, 3-octylacetamide, 4-octylacetamide
Tricyclene (8) has been oxidized in groups [37]. With Co(OAc)2 the hy-
acetic acid/Et3 N to the Nojigiku alcohol drocarbons: cyclohexane and norbor-
(9) in 77% yield (Eq. 8) [36]. The reaction nane have been indirectly oxidized in
was also conducted in a 2.25-kg scale CF3 CO2 H/CH3 CO2 H to the correspond-
to afford pure (9) in 65% yield from ing ketones in 47 to 52% yield [38].
crude (8) containing alkenes. The olefins
remained unconverted due to their higher 5.2.4
oxidation potential. Oxidation of Hydrocarbons in Fuel Cells
1. −2e, In fuel cells, the combustion energy of

AcOH, hydrocarbons can be converted directly
4F/mol into electrical energy. At the fuel cell
HO
2. −OH anode, the hydrocarbon is in most cases
H converted to carbon dioxide because the
(8) (9) intermediates are more easily oxidized
(8) than the starting hydrocarbon (Eq. 9a); at
By indirect oxidation with electro- the fuel cell cathode oxygen is reduced
generated NO•3 radicals in t-butanol/ to water (Eq. 9b). Most fuel cell research
water/HNO3 /O2 , saturated hydrocarbons has involved the use of hydrogen as fuel.
were oxidized to ketones with a sta- However, solid oxide fuels cells (SOCFs)
tistical H-abstraction at the methylene can operate at higher temperature and can
use dry hydrocarbons as fuels [39, 40]. potential of alkenes can vary from less
than 0 V (vs. Ag/AgCl) for strong electron-
(a) CnH2n + 2 + 2n H2O
donating substituents, like the dimethy-
n CO2 + (6n + 2) e + (6n + 2) H+ lamino group, till up to 2.5 V for hydrogen
and electron withdrawing groups as the
(b) (6n + 2) e + (6n + 2) H+ + 0.5 (3n + 1) O2
ester group. A selection of oxidation po-
(3n + 1) H2O
tentials for substituted alkenes is found in
(9) Refs. [5, 47, 48].
Only in few cases, substitution, dehy- Electron transfer from the alkene leads
drogenation, or coupling products of the to a radical cation that can undergo
hydrocarbon are obtained. The selective coupling (Scheme 1a). The radical cation
dehydrogenation of short-chain hydrocar- can also react with the nucleophilic
bons is reported for higher temperatures. heteroatom of a reagent to afford addition
Ethane is dehydrogenated at 700 ◦ C in the or substitution products (Scheme 1b).
presence of oxygen to ethene with 10.6% Adducts can be likewise obtained by
conversion and 96.9% selectivity [41]. In a oxidation of the nucleophile to a radical
mixed oxide consisting of Mo/Bi/Ni/Fe that undergoes radical addition. Reactions
Si/K/Na, a propene has been oxidized between alkenes and nucleophiles can be
to acroleine [42]. The dehydrodimeriza- realized too with chemical oxidants that
tion of short-chain hydrocarbons has also are regenerated at the anode (mediators)
been achieved. The oxidative coupling of (see Chapter 15). Finally, cycloadditions
methane at an Ag/Bi2 O3 electrode in a between alkenes can be initiated by a
solid electrolyte yielded at 700 ◦ C and catalytic anodic electron transfer. These
2% conversion in 72% selectivity ethane principal reaction modes are subsequently
and in 18% selectivity ethene [43]. Further illustrated by selected conversions.
dehydrodimerizations of methane at 500
to 900 ◦ C are reported for a Y2 O3 /ZrO2 5.3.2
solid electrolyte and different anode ma- Anodic Coupling of Alkenes by Way
terials like Ag, Ni, Cu, Bi, Pt, Sm, and of Radical Cations
Mn [44–46].
5.3.2.1 Intermolecular Coupling
Olefins with electron-donating sub-
5.3 stituents as the alkoxy, acylamino, phenyl,
Anodic Oxidation of Alkenes or vinyl group can be coupled in methanol
5.3.1 to give 1,4-dimethoxy dimers and/or di-
General Reaction Behavior enes (Scheme 2). The first intermediate in
this coupling reaction is a radical cation,
Alkenes are in general oxidized easier which either by electrophilic addition to
than the corresponding alkanes because the olefin and subsequent 1e-oxidation
the HOMO of the π-bond from which (path A) [49] or by radical dimerization
the electron is transferred to the anode (path B) [50, 51] leads to a dimer di-
has a higher energy than the HOMO cation that undergoes methanolysis or
of the σ -bond in the corresponding deprotonation. Representative examples of
alkane. Depending on the substituents at this coupling reaction are summarized in
the olefinic carbon atom, the oxidation Table 7.
5.3 Anodic Oxidation of Alkenes 135
−e Y Y
Y
OMe +
CH3OH MeO
Y Y
−e
2MeOH
−2H −2H
Y
−e
• Y
Y+ A
B
•
Y
Y+
Y = Ph, OR, OSiMe3, NHCOR
Scheme 2 Anodic coupling of alkenes.
Tab. 7 Anodic oxidation of ethylenic compounds
Nr. Substrate Conditions Products Yield [%] Refs.
1 Styrene MeOH, NaOAc, Ph CH CH2 )2 64 52

NaClO4 , C
OMe
2 α-Methylstyrene MeOH, NaOAc, Ph H 64 52

NaClO4 , C
)
Me 2
3 Styrene CH2 Cl2 -H2 O, 52 53, 54

TBAHSO4 Ph Ph
O
4 Vinyl ethyl ether MeOH, Nal, C MeO 51 56, 58
EtO CH CH2 )2
5 1-Ethoxycyclohexene MeOH, NaClO4 , O 48 58

2,6-lutidine, C
)2
6 OTMS CH2 Cl2 , MeOH, O 50 59

Bu4 NBF4
)
7 OTMS MeCN, MeOH, O 78 59

LiClO4
)2
(continued overleaf )
Tab. 7 (continued)
Nr. Substrate Conditions Products Yield [%] Refs.
8 1,1-Bis(dimethyl- DMF, Et4 NClO4 ((Me2N )2 CH CH )2 – 60, 61

amino)-ethylene
9 Butadiene C, MeOH, )2 17 65
NaClO4
MeO
OMe 16
MeO
)2 16
OMe
10 Methylenecyclohexane C, MeOH, OMe 38 67

NaClO4
)
2
11 α-Methylstyrene, vinyl C, MeOH, OMe OEt 32 68

ethyl ether NaClO4
Ph C(Me) CH2 CH2 CH
OMe
Styrene and indene derivatives compounds in 30 to 60% yield (Table 7,

(Scheme 2, Y = Ph) are dimerized to numbers 4, 5) [55–57].
1,4-dimethoxy-1,4-diphenylbutanes or 1,4- Silyl enol ethers (Scheme 2, Y = OSi
diphenylbutadienes (Table 7, numbers 1 (CH3 )3 ) can be dimerized to 1,4-dicarbonyl
and 2) [52]. The product distribution is compounds in good yields. To suppress
in some cases strongly dependent on the methanolysis of the silyl enol ethers,
the anode potential and the supporting MeCN-5% MeOH is used as solvent and
electrolyte. Dimerization is promoted by the electrolysis is conducted within one
α-substituents that stabilize the interme- hour by the use of a capillary gap cell, which
diate radical cation, for example, phenyl, allows high currents (Table 7, numbers 6
vinyl, alkoxy, dialkylamino groups. ß-Alkyl and 7) [59].
substituents strongly decrease the yield of Examples of the coupling of enam-
dimers and favor formation of dimethoxy- ines are rare [60]. In most cases, the
lated monomers. enamines undergo methanolysis to form
Enol ethers (Scheme 2, Y = OR) with electroinactive aminoacetals prior to the
half-wave potentials between E1/2 = +1.2 coupling reaction. Enamino ketones or
and +1.8 V (Ag/AgCl) couple in methanol enamino esters, however, yield via dimer-
with 2,6-lutidine as base at a graphite ization of the radical cations and sub-
anode to give the acetals of 1,4-dicarbonyl sequent ring closure pyrrole derivatives
(Eq. 10) [62–64]. Unsymmetrical dimers are accessi-

ble through the coelectrolysis of differ-
X X ent olefins (Table 7, number 11). Cou-
HC CH pling can also be achieved by the ad-
NHR2 −2e
CH C dition of anodically generated radicals
R1 C C with subsequent dimerization of the
X R1 R1 adduct radicals (additive dimerization, see
NH NH
Section 5.3.3).
R2 R2
−H+ X X 5.3.2.2 Intramolecular Coupling
−R2NH3+
The intramolecular coupling of enolethers
with enolethers, styrenes, alkyl-substituted
R1 N R1
olefins, allylsilanes, and vinylsilanes was
R2 systematically studied by Moeller [69].
Many of these coupling reactions turned
X = CO2Me, COMe, CN
out to be compatible with the smooth
R1 = CH3, H, 4-MeO-C6H4 formation of quaternary carbon atoms
R2 = H, Me, CH2C6H5, Ph (Eq. 11) [70], which were formed diastere-
9−54% oselectively and led to fused bicyclic ring
(10) skeletons having a cis-stereochemistry [71].
Dienes [Scheme 2, Y = vinyl] are dimer- The cyclization is compatible with acid-
ized to dimethoxyoctadienes or are di- sensitive functional groups as the allylic
methoxylated to dimethoxybutenes at alkoxy group. Moeller has demonstrated
graphite, platinum, or glassy carbon an- in some cases that these reactions can be
odes in an electrolyte consisting of run without loss of selectivity and yield in
methanol–sodium perchlorate (Table 7, a simple beaker with either a carbon rod
number 9) [55, 65]. Dimerization is fa- or reticulated carbon as anode without po-
vored by graphite or carbon cloth anodes, tential control and a 6-V lantern battery as
by high olefin concentrations and by ter- power supply [71].
minally unsubstituted dienes [65, 66]. The
ratio of monomer to dimer is determined MeO
mainly by the anode material. Anodes
with a smooth surface, such as platinum,
gold, and glassy carbon, promote the for-
mation of monomers; porous materials, O TMS
TBDMS
such as soft graphite or carbon cloth, fa-
vor the dimers. Alkenes without (+)-M OTBDMS
substituents can be coupled if they are a, 75% MeO
dialkylated at one carbon atom of the MeO
double bond and are unsubstituted at H
the other (Table 7, number 10). This is
a further indication that the dimerization a : C-anode, 1 M LiClO4, MeOH/THF,
of radical cations responds sensitively to lutidine
steric hindrance. (11)
Unsaturated enol acetates (10) have been addition to the double bond and the result-
cyclized to cyclohexenylketones [72]. ing cation (14) is subsequently trapped by
methanol to afford (12).
OAc Further examples of intramolecular cou-
R2 pling have been summarized in the litera-
R1 ture [75, 76].
(10) 5.3.3
Anodic Substitution and Addition via
Swenton has explored the dependence of Radical Cations
yield and selectivity in the intramolecular
coupling between phenols and olefins on Anodic addition of nucleophiles to olefins
the substituents in the aryl ring and the can be achieved via oxidation of the
olefin (Scheme 3) [73, 74]. alkene to a radical cation.This means
Oxidation of the phenol (11), deprotona- that a nucleophile can be added to
tion and a further electron transfer leads a nucleophilic alkene by reversing its
to (13), which undergoes an electrophilic polarity to an electrophilic radical cation
R1 R2 R2
R1 OMe
a
HO
O
(11) (12)
−2e +MeOH
−H+ −H+
R1 R2 R2
R1
+
O +
O
(13) (14)
R1 R2 Yield
(%)
H H 16
H CH3 85
H Ph 65
CH3 H 35
69
−(CH2)3−
a: Pt anode, CH3CN/MeOH/AcOH, LiClO4
Scheme 3 Intramolecular coupling between phenol and alkene.

at the anode. In the usual additions (Scheme 4, (21), Nu = OCH3 ) are formed
to olefins an electrophile is added in nearly exclusively. In acetic acid, the cor-
the first step. The anodic addition of responding acetate is found and in ace-
methanol to cyclohexene (15, Nu = CH3 O, tonitrile an N -acetyl amine via reaction of
Scheme 4) to afford (21)–(23) illustrates (18) with the nitrogen of acetonitrile is
well the competing pathways. The first obtained [78, 79].
formed radical cation (16) can react with Allylic CH bonds can be substituted
the nucleophile to form via (17) the fairly regioselectively by using an in-
carbenium ion (19). In competition (16) tramolecular reaction (Eq. 12) [80] or suit-
can be deprotonated and the formed able substitution (Eq. 13) [81].
radical oxidized to the allyl cation (18).
−e
Methanolysis of (18) leads to (21) as does
the deprotonation of (19). The carbocation OH TEATOS, O
(19) can furthermore undergo a 1,2- CH3CN
carbon shift to form via (20) the acetal 26%
(23). Furthermore, (19) reacts in a minor (12)
pathway with a second nucleophile to yield OAc O
the bisadduct (22) [77]. −e
The basicity or acidity of the electrolyte, TEATOS,
and in particular, the methanol concen- CH3CN
tration, strongly influences the product 90%
distribution. With an equimolar mixture (13)
of cyclohexene and methanol in tetrahy- Generation of hypochloric acid at the
drofuran, 81% of 3-methoxycyclohexene anode allows allyl substitution via an
−e NuH,
+ • −H+, −e
•
Nu
(15) (16) (17)
+
−H −e
−e −H+
1,2-shift +
+
Nu
Nu
(18) (19) (20)
HNu
NuH −H+
−H+
−H+ NuH Nu
Nu
−H+
Nu
Nu Nu
(21) (22) (23)
Scheme 4 Anodic substitution and addition with cyclohexene (15) via a radical cation.
ene-reaction in high regioselectivity and

yield [82]. ß-Ionone has been acetoxylated
in the allylic C4 position in excellent CH3CN, −e
H3CN NCH3
yield [83]. With α- and β-pinene anodic al-
CH3NHCONHCH3 O
lylic methoxylation is achieved by cleavage
50%
of the four-membered ring [84]. Enam-
ines afford mixtures of allylic and vinylic (15)
methoxylation in 74 to 76% yield [85]; Dienes can undergo 1,2- and/or 1,4-
besides, methanol also enolates from CH- addition [65]. 1,3-Bisnucleophiles, as 1,3-
acidic compounds, for example, methyl dimethylurea, favor 1,2-addition due to
acetoacetate, can be introduced (Table 8, the formation of a five-membered ring
(Eq. 15) [90]. Furan and its derivatives
number 3).
undergo a clean 1,4-addition, which is
Bisalkoxylations are rare with alkyl-
mediated by NH4 Br [91] and has been
substituted alkenes, but can become a
also used for a technical scale conver-
major portion of the products with eno- sion [92]. N -Acetylindole reacts in a 1,2-
lethers [55, 56, 58], 1,3-dienes [55, 65, 86, bisacetoxylation because the phenyl ring
87] or arylolefns [52, 53], especially, when wants to regain aromaticity [93].
the terminal position of the alkene bears
alkyl substituents that disfavor dimeri- 5.3.4
zation. Addition via Oxidation of Nucleophiles to
Intramolecular addition can occur when Radicals
nucleophilic substituents are suitably po-
If anions R− are oxidized in the pres-
sitioned as in Eq. 14 [88]. When the latter
ence of olefins, additive dimers (24) and
electrolysis is conducted in CH2 Cl2 /Bu4 substituted monomers (26) are obtained
NCl, 75% of the chloro-γ -lactone are (Scheme 5, Table 8, and Ref. [94]). The
obtained. Electrolysis of (E)-5-phenyl- products can be rationalized by the fol-
4-pentenoic acid affords a 4-(phenyl- lowing pathway: the radical R• obtained by
methoxymethyl)-4-butanolide [89]. a 1e–oxidation from the anion R− adds
to the alkene to give the primary adduct
(25), which dimerizes to afford the additive
O dimer (24) with regiospecific head-to-head
O connection of the two olefins, or couples
CO2H with R• to form the additive monomer (26).
MeCN, H2O
LiClO4, −e If the substituent Y in the olefin can sta-
bilize a carbenium ion, (25) is oxidized to
44% the cation (27), which reacts intra- or inter-
O molecularly with nucleophiles to give (28)
O
or (29).
+ + O Satisfactory to good yields of adducts
O have been found for styrenes (Scheme 5,
Y = phenyl), conjugated dienes (Y =
38% 12% vinyl), enamines (Y = NR2 ), and enol
(14) ethers (Y = alkoxy), particularly if they are
Tab. 8 Addition of Anodically Generated Radicals to Alkenes
Nr. Radical precursor, Olefin Conditions Product Yield [%] Refs.
Anions of 1,3-dicarbonyl compounds

1 MeO2 CCH2 COMe MeOH, MeONa, Pt O 36 95
H2 C=CHOEt
MeC
Me O OEt
2 O MeCN, Et4 NOTos O 85 96
O O Ph
PhCH CH2
3 CH3 COCH2 CO2 CH3 CH3 ONa, MeOH O 67 97
Morpholino-
cyclopentene COCH3
N
CH
CO2CH3
4 (MeO2 C)2 CH2 MeOH, MeONa, Pt MeO2C 40 95
Styrene
MeO
MeO O Ph
5.3 Anodic Oxidation of Alkenes
141
142
Tab. 8 (continued)
Nr. Radical precursor, Olefin Conditions Product Yield [%] Refs.
Anions of 1,3-dicarbonyl compounds

5 (MeO2 C)2 CH2 MeOH, MeONa, Pt [(MeCO)2 CHCH2 CH=CHCH2 ]2 46 95
Butadiene +isomers
6 CH3 COCH2 CO2 C2 H5 HOAc/EtOAc CO2Et 80–86 98
R2 NaOAc, 0.1 eq.
R2
Mn(OAc)2 Me
R1
CH2 C-anode O
R1
R1 = propyl
pentyl, t-butyl
R2 = H, methyl
7 CO2Et KOAc/HOAc, 0.25 CO2Et 40–91 99
Ph eq. Mn(OAc)2 CO2Et
CO2Et C-anode
R C CH
5 Anodic Reactions of Alkanes, Alkenes, and Aromatic Compounds
R
R: C6H13, (CH3)3Si,
Ph
8 (CH3 )2 CHNO2 , Styrene MeOH, MeONa, Pt NO2 Ph 43 100
(CH3)2C CH2 CH OMe

9 nBuMgBr, Styrene (C2 H5 )2 O, LiClO4 , (nBuCH2 CHPh)2 29 101
Pt
Carboxylates
10 EtO2 CCO2 H, Butadiene MeOH, Pt (EtO2 CCH2 CH=CHCH2 )2 + isomers 66 102
EtO2 CCH2 CH=CHCH2 CO2 Et 4
11 MeO2 C(CH2 )4 CO2 H MeOH, Pt MeO2 C(CH2 )12 CO2 Me 92–95 103
Ethylene MeO2 C(CH2 )10 CO2 Me
12 MeO2 CCH2 CO2 H MeOH, Pt [MeO2 C(CH2 )2 CHPh]2 38 102
Styrene
13 MeO2 C(CH2 )4 CO2 H MeOH, Pt [MeO2 C(CH2 )5 CH=CHCH2 ]2 4747 104
Butadiene MeO2 C(CH2 )5 CH=CH(CH2 )5 CO2 Me
14 F3 CCO2 H, CH2 =CHnPr MeCN, NaOH, Pt [CF3 CH2 CH(nPr)]2 40 105
15 CH3 CO2 H MeCN, H2 O, Pt [CH3 −CH2 C(CH3 )(CHO)]2 80 106,107
Methacroleine
16 CF3 CO2 H, Vinyl acetate MeCN, H2 O, NaOH [CF3 CH2 CH(OAc)]2 14 108
17 CH3 CO2 H, Dimethyl MeCN, H2 O [MeO2 C(CH3 )CH]2 80 109
fumarate
18 CO2H 5% MeONa, MeOH OMe 41 110
H O
O
MeO2C(CH2)CO2H O
H
19 CO2H 5% MeONa, MeOH MeO2C(CH2)4 53 111
N N
COMe COMe
MeO2C(CH2)4CO2H
5.3 Anodic Oxidation of Alkenes
143
Y Y
R R R
−e (24)
Y Y
R• R •
(25)
Y
R•
R R −e R R
(26)
Y Y Y
Nu−
R + R Nu
R1
(27) (28) (29)
Scheme 5 Addition of anodically generated radicals to alkenes.
unsubstituted at the carbon atom in β- additive monomers [114]. NO3 • -radicals

position to Y . Nonactivated alkenes react can be prepared by anodic oxidation of
less satisfactorily. nitrate anion. In the presence of terminal
In the oxidation of anionized 1,3- and vic-disubstituted olefins, nitrate esters
dicarbonyl compounds (Table 8, numbers are obtained [115]. With an aldehyde and
1–7) at potentials between 0.6 and 1.4 V nitrate anion, acyl radicals are generated
(sce) and in the presence of butadiene, that afford 1,2-bisadducts with activated
mainly the additive dimer (24) is ob- olefins [116].
tained; in the presence of ethyl vinyl ether If carboxylates are subjected to Kolbe
chiefly the disubstituted monomers (28) or electrolysis in the presence of olefins, the
(29) arise. generated Kolbe radicals add to the double
In the addition to nonactivated alkenes, bonds to afford mainly additive dimers
where the direct anodic oxidation is (Table 8, entries 10–17).
less, satisfactorily good yields can be Upon electrolysis of trifluoroacetate in
achieved when Mn(OAc)2 is used as MeCN-H2 O-(Pt) in an undivided cell
mediator (Table 8, entries 6, 7). Sorbic in the presence of an electron, defi-
acid precursors have been obtained in cient olefins additive dimers and additive
larger scale and high current efficiency monomers are obtained. The selectivity
by a Mn(III)-mediated oxidation of acetic can be controlled by current density, tem-
acid/acetic anhydride in the presence of perature, and the substitution pattern of
butadiene [112]. the olefin [117].
Also other anions, such as the 2- The influence of mechanism and ki-
nitropropanate anion, Grignard reagents netic data on yields and selectivities in
(Table 8, numbers 8 and 9), and bo- addition reactions of anodically generated
rates [113], can be added to olefins. radicals to olefins has been calculated and
Also azide radicals generated by anodic the predictions tested in preparative elec-
oxidation of sodium azide in the presence trolyses [118].
of olefins afford in acetic acid additive Good yields can be obtained with
dimers, products of allylic substitution and nonactivated alkenes, when the reaction
is conducted intramolecularly. β-Allyloxy- rate of the mostly nucleophilic Kolbe-

and β-allylaminopropionates cyclize in radical. With electron-attracting groups at
a mixed Kolbe electrolysis by way of the double bond, the yield of cyclized
an intramolecular addition (5-exo-trig cy- product increases from 21% to more than
clization) and a subsequent heterocou- 70% (Eq. 16) [121]. For a more detailed
pling of the exocyclic radical to form discussion, see the literature [122].
3-substituted tetrahydrofurans and pyrro- A radical tandem cyclization, consisting
lidines (Table 8, numbers 18 and 19). This of two radical carbocyclizations and a het-
intermolecular addition has been used to erocoupling reaction, has been achieved
synthesize a precursor of prostaglandin by electrolysis of unsaturated carboxylic
PGF2α [119, 120]. acids with different coacids. This provides
The extension of the cyclization from a short synthetic sequence to tricyclic prod-
tetrahydrofurans and pyrrolidines to car- ucts, for example, triquinanes, starting
bocycles leads to a sharp decrease in the from carboxylic acids which are accessible
yield of cyclized product. This is due to the in few steps (Scheme 6) [123]. The selec-
slower cyclization rate of 5-hexenyl radi- tivity for the formation of the tricyclic, bi-
cals compared to 5-(3-oxahexenyl) radicals, cyclic, and monocyclic product depending
which favors the competing bimolecular on the current density could be predicted
coupling to the acyclic product. Three mea- by applying a mathematical simulation
sures help to increase the yield in these based on the proposed mechanism.
cyclizations. Radical cyclizations of this type can be
also achieved in chemical radical chain
CO2H −H+, −e, −CO2
reactions [124, 125], often in a wider
R1 scope. The anodically initiated cyclization,
+R3CO2H however, has advantages. It avoids tin
R2 R2 hydride, which is mostly used as coreagent
in chemical radical chain cyclizations and
R3 because the toxicity of tin organics makes
R1 these reactions less attractive for the
synthesis of pharmaceuticals. In chemical
radical chain reactions, which involve in
R2 R2
most cases an addition and an atom-
transfer reaction, one C,C- and one C,H- or
R1 R2 R3 yield C,X bond is being formed, while in anodic
(%)
addition followed by heterocoupling two
CN CH3 (CH2)4CO2CH3 75 C,C bonds are being formed, where the
CO2Et CH3 (CH2)4CO2CH3 76 second one is established simply and in
CN H (CH2)4CO2CH3 71 wide variety by the appropriate choice of
COCH3 H CH3 71 the coacid.
(16) 5.3.5
These are the use of the geminal dialkyl Mediated Oxidation of Alkenes
effect, the decrease of the current density
and especially the use of an electrophilic Alkenes, as other organic substrates, can
double bond that increases the addition be converted by indirect anodic oxidation.
O 1. LDA O
2.
I CO2Na (85%) 5. eq. CH3CO2H
3. C4H7MgBr −e, −CO2
OEt 4. H+ (74%)
CO2H
O O O
+ +
42% 15% 8%
2 diastereomers 2.7 : 1
Scheme 6 Radical tandem cyclization to tricyclic compounds.
Here a mediator serves as an oxidant In enzymatic syntheses, the use of me-

that enables the selective introduction diated reactions for the regeneration of
of a functional group. The mediator is enzymes and cofactors becomes increas-
thereby reduced and can be regenerated ingly important [129].
at the anode, so that it acts as a
redox catalyst (Eq. 17). The method is 5.3.6
very powerful, as very selective oxidants, Anodically Induced Cycloadditions
whose use is limited to smaller amounts
due to their price, can be applied in [4 + 2]- and [2 + 2]-cycloadditions can be
catalytic quantities amounts for larger induced by electron transfer. In a radi-
scale conversions. cal chain reaction, the olefin is oxidized
to its radical cation, which undergoes a
−e cycloaddition. The distonic dimer radi-
(a) Medred Medox
cal cation then accepts an electron from
(b) Ol + Medox the olefin to undergo ring closure and
to initiate a new cycle (Eq. 18) [130]. This
Olf + Medred way vinyl carbazole (Table 9, number 1)
and 5,6-dimethoxyindene [131] have been
Med = mediator, cyclized. Indenone also reacts in an electro-
Olf = functionalized ofefin catalyzed [4 + 2]- and [2 + 2]-cycloaddition
(17) with styrene derivatives [132]. Further-
This wide field is covered separately in more, a series of dienes has been subjected
Chapter 15 of this book. Further reviews to to [4 + 2]- and [2 + 2]-cycloadditions with
this topic can be found in Ref. [126–128]. Ar3 N+• as mediator (Table 9, numbers 2
Tab. 9 Cycloadditions of anodically generated intermediates
Nr. Olefin Conditions Product Yield [%] Ref.
1 Fe(NO3 )3 , 80 130
MeOH
N
N
2 1,3-Cyclohexadiene MeCN, CH2 Cl2 24 133

lutidine, Ar3 N
3 CH3O LiClO4 73 134

CH3 NO2 MeO
4-CH3O-C6H4
4-CH3O-C6H4
4 HO H2 O, NaOAc OH 95 135
O
HO OH
OH
O O
O O
and 3). are generated electrochemically and then

react with the olefin to form an adduct
Y that stabilizes itself by reaction with a
2 nucleophile or by deprotonation. This way,
Y Y ortho-phenols react with enols presumably
−e +e via an ortho-quinone as intermediate
Y (Table 9, number 4).
Y In the synthesis of an euglobal skeleton,
•
+ • a quinone methide has been generated
Y Y in situ by anodic oxidation mediated
(18) by DDQ. The cycloaddition with un-
In other cases, the cycloadditions are not activated alkenes was promoted by the
electrocatalytic. The reactive intermediates use of lithium perchlorate/nitromethane
and a hydrophobic PTFE-coated electrode The three pathways depended strongly

(Scheme 7) [136]. on the configuration of the double
The intramolecular coupling of phe- bond and the nature of the functional
nol derivatives with olefins is a very groups attached to the double bonds.
useful C,C bond-forming reaction. Ya- The synthetic possibilities have been
mamura has shown that this reac- nicely summarized with some retrosyn-
tion can lead to three different prod- thetic analyses of the target molecules by
uct types (30a–c) (Scheme 8) [137, 138]. Moeller [139].
O a
O OH
HO OH
+ Cl CN Cl CN
Cl CN Cl CN
O OH
O HO
DDQ −2e
a : PTFE-coated Pt-electrode
O O
HO O LiClO4
HO O
CH3NO2
O OH O OH
74%
Scheme 7 [4 + 2] – Cycloaddition with anodically generated quinone methide.
MeO OH 2 MeO O
R R3 −2e, −H+ R2 R3
+
R4 R4
MeO MeO
R1 R5 R1 R5
R2
R1 R2
O O R4 R1
O O
R5
MeO R3 R3
MeO R3
R1 R5
R5 MeO
O R4 R2 R4
O
(30a) (30b) (30c)
Scheme 8 Anodic intramolecular coupling of phenols with olefins.

5.4 Anodic Oxidation of Aromatic Compounds 149
5.4 among others on the charge distribution in

Anodic Oxidation of Aromatic Compounds the radical cation. A high positive charge
density at the unsubstituted aromatic
5.4.1
carbon atom favors products (31) and (36),
General Principles of Reaction
while a high positive charge density at
an aromatic carbon atom adjacent to an
Anodic conversion of aromatics proceeds
alkyl substituent supports the formation of
in most cases by 1e-transfer to the anode
(32) or (37) [143]. The selectivity, however,
to form a radical cation (34) (Scheme 9).
is not always pronounced. Investigations
Oxidation is facilitated by extension of
on the mechanism of these reactions
the π-system (E1/2 vs. Ag/Ag+ benzene
and the evolving general as well as
2.08 V, pyrene 0.86 V) and by electron
individual patterns can be found in
donating substituents (E1/2 vs. Ag/Ag+ p-
Ref. [144–146].
phenylenediamine −0.15 V). Oxidation
potentials of polycyclic aromatics and
substituted benzenes are collected in R R
Ref. [140–142].
CH2 CH2
The radical cation (34) can react along
the following pathways:
a. It can undergo a radical–radical cou-

pling reaction with subsequent rearom- CHR
atization by deprotonation to form
biphenyl compounds (31) (Scheme 9).
This pathway is supported by electron- CH2
(32)
donating substituents that stabilize the R
coupled σ -intermediate. (31)
b. The radical cation can react with
(a)
a nucleophile to afford a nuclear (c) (33), −H+
(34) −2H+
substitution product.
c. It can be deprotonated in the benzylic R R R
position to form, after a further electron
CH2 CH2 CH+
transfer to the anode, a benzyl cation
(35), which can undergo an electrophilic −e −H+
+
•
aromatic substitution at (33) to yield a −e
diphenylmethane derivative. (33) (34) (35)
d. The benzyl cation can react with a
(b) HNu HNu
nucleophile to lead to a side chain −e (d) −H+
−2H+
substitution product.
R R
The product distribution between reaction CH2 CH Nu
in the nucleus or in the side chain depends
Scheme 9 Reaction pathways of

anodically generated aromatic Nu
radical cations. (36) (37)
5.4.2 For mesitylene and durene, the kinetics

Anodic Coupling have been followed by specular reflectance
spectroscopy [159]. The results indicated
Representative couplings of aromatic
hydrocarbons are summarized in Table 10. that mesitylene produces a fairly stable rad-
Alkyl-substituted aromatic hydrocarbons ical cation that dimerizes. That of durene,
can be coupled to diphenyls and/or however, is less stable and loses a proton to
diphenylmethanes depending on their form a benzyl radical, which subsequently
substitution pattern (Table 10, numbers leads to a diphenylmethane. The stability
1–6). Reactions occur according to of the radical cation increases with in-
Scheme 9, paths (a) and (c). creasing charge delocalization, blocking of
Tab. 10 Anodic coupling of aromatic hydrocarbons
Nr. Substrate Conditions Products Yield [%] Ref.
1 p-Xylene C, CH2 Cl2 , TFA, 22 147

TBABF4
2 1,2,4-Trimethyl- C, CH3 NO2 , 17 148

benzene Bu4 NBF4 (CH3)2
(CH3)2
21
(H3C)2 (CH3)2
3 1,3,5-Trimethyl- Pt, Bu4 NBF4 , 71 149

benzene CH3 CN
)2
4 5-Alkyl-substituted 4–82 150

m-xylenes )2
R
R = Me, Et, i-Pr, t-Bu
5 1,2,4,5-Tetramethyl- C, CH2 Cl2 , TBABF4 85 147

benzene
Tab. 10 (continued)
6 2-Methyl- C, CH3 CN/H2 O 2 45 151
(
naphthalene NaBF4
28
(
2
7 Anthracene MeCN, EtOH, O 91 152

LiClO4
( 2
8 9-Phenyl-anthracene TEAClO4 , MeCN Ph 37 153

(
9 1,5-Dichloro- MeCN, EtOH 1,1 ,5,5 -Tetrachlorobianthrone 75 154

anthracene
Mixed coupling
10 Naphthalene, Pt, Bu4 NBF4 , 1, 1 -Binaphthyl 22 155

mesitylene MeCN, AcOH
19
11 Naphthalene, Pt, Bu4 NBF4 , 1, 1 -Binaphthyl 1.6 156

pentamethyl- MeCN, AcOH
benzene
64
Tab. 10 (continued)
12 Hexamethylbenzene Pt, CH2 Cl2 : TFA Ar 8–66 157

and aromatic (9 : 1), TBABF4
hydrocarbons
(benzene,
toluene, p-xylene,
mesitylene)
13 Anthracene, anisole Pt, Bu4 NBF4 , OCH3 70 158

CH2 Cl2 -TFA-
TFAn
(47 : 2 : 1)
OCH3
reactive sites, and stabilization by specific acetamides, which are formed in a Rit-
functional groups (phenyl, alkoxy, and ter reaction, are often the major products.
amino) [160]. The complex reaction mech- The selective dimerization of mesitylene
anisms of radical cations and methods of in acetonitrile is exceptional (Table 10,
their investigation have been reviewed in number 3).
detail [161]. Mixed coupling between naphthalene
To favor the coupling reaction, the and alkyl benzenes has also been demon-
competing side reaction of the radical strated (Table 10, numbers 10–13). The
cation with nucleophiles must be sup- relative yield of mixed coupling prod-
pressed by the use of a medium of ucts increases with the basicity of the
low nucleophilicity. The solvent of choice alkyl benzene; with mesitylene 19%, with
is dichloromethane. Especially in elec- tetramethylbenzene 42%, and with pen-
troanalytic studies, neutral alumina is tamethylbenzene 64%. This suggests an
frequently added to suppress hydroxy- electrophilic reaction between naphtha-
lation of the radical cation [162]. The lene cation radicals and alkylbenzenes.
reversible cyclic voltammetric behavior The mixed coupling reaction of phenan-
of radical cations is also enhanced in threne with anisole has been studied
mixtures of methylene dichloride, triflu- kinetically [163].
oroacetic acid, and trifluoroacetic anhy- Bibenzyls can be obtained in a remark-
dride (TFAn) with TBABF4 as supporting able reaction from toluene, p-xylene or
electrolyte. With acetonitrile as solvent ethylbenzene in 60 to 100% yield [164]. For
Tab. 11 Anodic coupling of phenols
Nr Phenol Conditions Products Yield [%] Ref.
1 o-Cresol PbO2 , H2 SO4 HO 5 171

Me
(
2
2 2,6-Dimethyl-phenol Pt, MeCN, NaClO4 , O 90 172

2,6-lutidine Me Me
(
2
3 2,6-Di-t-butyl-phenol MeOH/CH2 Cl2 , OH 93 173

LiClO4 , Pt, Me3C CMe3
periodic current
reversal in
divided cell
(
4 OH Glassy carbon, OH 41–100 174

MeO CH NR MeCN, NaClO4 MeO CH NR
R = i-Pr, t-But,
(
2
CH2CH(CH3)CO2H,
Me, Et, Benzyl
5 1,2-Dimethyl-7-hydroxy-6- Graphite felt, MeO 69a 175

methoxy-1,2,3,4- MeONa, MeCN,
tetrahydroisoquinoline TEAClO4 NMe
HO
(
2
Me
6 2-Acetyl-4-methyl-phenol 0.1 M NaOH, H2 O, O OH 26 176
MeOH, Pt
Me )2
Me
7 OH CH3 OH-ether, 1% tBu tBu 65 177
KOH
tBu tBu
O
OMe
O
tBu tBu
Tab. 11 (continued)
Nr Phenol Conditions Products Yield [%] Ref.
8 2-Methoxy-4-allyl-phenol Pt, MeOH-LiClO4 , 100 178

NaOH
)2
MeO
OH
9 Vanillin Pt, MeCN, NaClO4 , OH 65 179
Et4 NOH, 0.25 V MeO
(SCE) )2
CHO
a Only one of three possible diastereomers is obtained; additionally, 7% O-C coupling product is
found.
this reaction catalytic amounts of quinones The earlier literature on oxidative cou-
are irradiated in the presence of the alkyl- pling of phenols is reviewed in Ref. [168]
benzenes, and the anode potential is held and that on anodic coupling in Ref. [169,
at that of the quinone–hydroquinone cou- 170]; some examples of the coupling reac-
ple. The photo-excited quinone abstracts a tions are summarized in Table 11, see also
benzylic hydrogen to form a radical that Chapter 6.
dimerizes. The resulting hydroquinone is Phenols are coupled mostly in alkaline
reoxidized to the quinone. media by oxidation of the phenolates to
Cyanation of aromatic hydrocarbons, phenoxy radicals. However, coupling in
also a carbon–carbon coupling reac- neutral or acidic medium by way of phe-
tion, is achieved in the case of an- noxy radical cations and phenoxonium
thracene in MeCN-Et4 NCN to yield 54% cations as intermediates is also known.
9,10-dicyanoanthracene [165]. The cyana- To generate the phenolate ion, bases as
tion is simplified when it is carried alkali hydroxides, Et4 NOH or 2,6-lutidine
out in an emulsion system (aqueous are used. The anodically generated phe-
sodium cyanide, dichloromethane, and noxy radicals react by carbon–carbon and
TBAHSO4 ). Its synthetic utility in this carbon–oxygen coupling to dimers, which
mode has been demonstrated for the additionally can be further oxidized. This
preparation of 4-alkoxy-4-cyanobiphenyls, frequently leads to product mixtures that
a class of liquid crystals [166]. are synthetically not very useful. Blocking
Anions of CH-acidic compounds of the 2-, 4- or 6-position makes the cou-
(dimethyl malonate and nitromethane) can pling reaction more selective. Phenols with
be linked to aromatics (benzene, toluene, unsubstituted para-position usually form
naphthalene, and 1,4-dimethoxybenzene) para, para-coupling products as the ma-
when they are coelectrolyzed in jor dimer (Table 11, numbers 1–4). If the
methanol–sodium methoxide [167]. 4-position is blocked ortho, ortho-coupling
is the main reaction (Table 11, numbers (Scheme 9, path d). An increasing number
5–9). of alkyl substituents at the benzylic car-
The anodic coupling of aryl ethers is bon (toluene 28.6%, ethyl benzene 50.5%,
reviewed in Ref. [180]. Aryl ethers are isopropylbenzene 46.7% [191]) and elec-
more selectively coupled than phenols for trolytes of lower nucleophilicity (TBAOAc,
the following reasons: The carbon–oxygen HOAc [192]) favor side chain substitu-
coupling is made impossible and the or- tion. Table 13 presents some selected ex-
tho-coupling and the oxidation to quinones amples of aromatic nuclear substitution
become more difficult. A mixture of triflu- with different nucleophiles X− or HX
oroacetic acid (TFA) and dichloromethane (Eq. 19).
proved to be the most suitable elec-
trolyte [181]. TFA enhances the radical −2e
cation stability and suppresses the nucle- H + X−
ophilicity of water. Of further advantage (19)
is the addition of alumina or trifluo-
roacetic anhydride [182]. Table 12 com- X + H+
piles representative examples of the aryl
ether coupling. Nuclear methoxylation of substrates
The trimethylsilyloxy (TMSO) group is with high oxidation potentials proceeds
stable under the coupling conditions in unsatisfactorily because the product with
acetonitrile (Table 12, number 6). After the electron-donating methoxy group
oxidative dimerization the TMS-ether can is easier to oxidize than the starting
be mildly hydrolyzed (H+ and H2 O) to the compound. With naphthalene and an-
phenol or converted to a dibenzofuran. 1,2- thracene, this drawback is less pronounced
Dialkoxybenzenes have been trimerized (Table 13, number 1). For the methoxy-
to triphenylenes (Table 5, numbers 7, 8). lation of methyl cinnamates that already
The reaction product is the triphenylene bear methoxy substituents in the aromatic
radical cation, which is reduced to the ring, substitution has been investigated
final product either by zinc powder or in in neutral and basic medium with re-
a flow cell consisting of a porous anode gard to ring substitution (major product)
and cathode [188]. Anodic trimerization of and double-bond addition whose ratio
catechol ketals yields triphenylene ketals, depends on current density, cell type, elec-
which can function as a platform for trode material, solvent, substrate, and base
receptors, for example, in an artificial concentration [206]. Phenols have been
caffeine receptor [190]. converted to quinones (Table 13, number
2) and these by subsequent cathodic re-
5.4.2.1 Nuclear Aromatic Substitution duction to hydroquinones [194]. The direct
Nuclear aromatic substitution occurs by oxidation of naphthalenes yields naph-
way of an ECN ECB -sequence as shown in thoquinones in 20 to 30% yield; better
Scheme 9, path (b). It occurs at the carbon results (up to 95%) are obtained using in-
atom with the highest positive charge den- direct methods [197, 207]. Acetoxylation is
sity and in alkylbenzenes competes with a more favorable general route to produce
side chain substitution via an ECB ECN phenols by anodic substitution; they can
process by deprotonation of the rad- be easily hydrolyzed to phenols and are
ical cation to form a benzyl radical. less susceptible to further oxidations than
Tab. 12 Anodic coupling of arylethers
Nr. Aryl ether Conditions Products Yield [%] Ref.
1 Anisole Pt, CF3 CO2 OMe 63 181

H-CH2 Cl2
(1 : 2), Bu4 NBF4
)
2
2 1,2-Dimethoxy- CF3 CO2 H-CH2 Cl2 OMe 86 181

benzene (1 : 2), Bu4 NBF4 OMe
)2
3 1,2,4- OMe 85 183

Trimethoxy- MeO
benzene
OMe
MeO
OMe
OMe
4 2,5-Dimethoxy- MeCN, water, Me No yield 184
toluene TEAClO4 OMe given
MeO
OMe
MeO
Me
5 9-Methoxy- MeCN, TFA, OMe 95 185
anthracene Bu4 NBF4
(
6 2-Methoxy-1,4- CH3 CN, LiClO4 OMe 65 186

bis(trimethyl- OH
siloxy)benzene
OH
OMe
Tab. 12 (continued)
Nr. Aryl ether Conditions Products Yield [%] Ref.
7 1,2-Dimethoxy- CH2 Cl2 , TFA, MeO OMe 50 187

benzene Bu4 NBF4
MeO OMe
MeO OMe
8 O) MeCN or CH2 Cl2 , Cyclotrimer 30 188, 189

TFA
)
4 O
Tab. 13 Anodic nuclear substitution of aromatic compounds
Nr. Aromatic Compound X− or HX (eq. 19) Products Yield [%] Refs.
1 Naphthalene CH3 OH/KOH 1-methoxy- 21 193

naphthalene,
1,4-dimethoxy- 49
naphthalene,
1,2-dimethoxy- 20
naphthalene,
1,2,4-trimethoxy- 6
naphthalene
2 2,3,6-Trimethyl H2 O, acetone, 2,3,6-trimethyl- 85 194

phenol H2 SO4 , PbO2 benzoquinone
3 Anisol CH2 Cl2 , H2 O, RCO2 H, OCH3 51–63 195

Bu4 N+
O2CR
o:m:p=
51 : 1 : 48
4 Naphthalene NaOAc, HOAc 1-naphthylacetate 22 196

70–85 197
Tab. 13 (continued)
Nr. Aromatic Compound X− or HX (eq. 19) Products Yield [%] Refs.
5 Nitrobenzene CF3 CO2 Na/CF3 CO2 H NO2 60 198
O2CCF3
o:m:p=
22 : 59 : 19
6 Anthracene CH3 CN, (CF3 CO)2 O HNCOCH3 85 199

Bu4 NBF4
7 Naphthalene Aqueous NaCN, CH2 Cl2 , CN 69 166, 200,

emulsion 201
8 4-Cyanophenol H2 O, NaHCO3 , KI CN 97 202
I I
OH
9 4-t-Butyl-t- CH3 CN, Et4 NF·3HF tBut 63 203

butylbenzene
10 Hydroquinone CH3 OH, (CH3 O)3 P, H3CO 90 204

dimethyl ether (CH3 )4 NSO4 CH3
P(OCH3)2
H3CO O
11 O2N NO2 BuNH2 , DMF, Et4 NBF4 NHBu 30 205

O2N NO2
NO2
NO2
alkoxy products. (Table 13, number. 3–5). The anodic chlorination in some cases
Emulsion electrolysis has been success- allows one to achieve better regioselec-
fully applied with phase-transfer catalysts tivities than chemical alternatives (p/o
(Table 13, number 3), which allows the ratio of chlorotoluene in chlorination of
conversion of salts that are not or only toluene: anodic 2.2, chemical alternative
slightly soluble in organic solvents and 0.5–1.0) [215]. Anodic oxidation of iodine
which needs only small cell voltages due to in trimethyl orthoformate afforded a pos-
the high conductivity of the electrolyte. The itive iodine species, which led to a more
acetoxylation is also of technical interest selective aromatic iodination than known
because it affords in good regioselec- methods [216]. Aryliodination is achieved
tivity, α-naphthol (Table 13, number 4). in good yield, when an aryliodide is oxi-
With CF3 CO2 H/(CF3 CO2 )2 O also accep- dized in HOAc, 25% Ac2 O, 5% H2 SO4 in
tor substituted aromatic compounds can the presence of an arene [217, 218]. Alkyl
be acetoxylated (Table 13, number 5). Fur- nitroaromatic compounds, nitroaromatic
ther examples of the trifluoracetoxylation ketones, and nitroanilines are prepared in
to suppress follow-up reactions are pre- good yields and regioselectivity by addi-
sented in Ref. [208, 209]. A way to retard tion of the corresponding nucleophile to a
side chain acetoxylation in alkyl benzenes nitroarene and subsequent anodic oxida-
is by electrolysis in an undivided cell in tion of the σ -complex (Table 13, number
the presence of Pd on charcoal. By hy- 11) [219, 220].
drogenolytic cleavage of the benzyl acetate,
the unwanted competition product is re- 5.4.2.2 Anodic Side Chain Substitution of
converted into starting material [210]. As Aromatic Compounds
substituents also the acetamido (Table 13, Anodic side chain substitution is a com-
number 6) [211], thio [212], cyano [165, peting reaction to nuclear substitution of
166, 213, 214], halo (Table 13, Nr. 9) [215] aromatic compounds. In side chain substi-
and phosphite (Table 13, Nr. 10) can be tution, the first formed acidic radical cation
introduced. With the cyano group, an ipso is deprotonated at the α-carbon atom of an
substitution of the methoxy group is ob- alkyl group to form a radical. This is fur-
served (Eq. 20) [165]. ther oxidized to a benzyl cation, which
reacts with a nucleophile (Scheme 9, path
CN− d). The factors that influence the ratio of
nuclear to side chain substitution have
OMe NC OCH2 H been described in 5.4.1.
TEACN The conversion to the monosubstitution
CH3CN + product can in some cases be controlled by
−e the oxidation potential or the substituent
OMe OMe
at the aryl group (Table 14, number 1–3).
CN Further examples of technical interest can
−CH2O
be found in Ref. [221].
In the case of the steroid (38), anodic
−HCN
substitution allowed the selective substi-
OCH3 tution of the benzylic hydrogen atom by
95% a methoxy group, whose elimination af-
(20) forded (39) and overall led in a three
Tab. 14 Anodic side chain substitution
Nr. Aromatic Compound X− or HX Products Yield [%] Ref.
1 4-Acetoxy-toluene HOAc, 4-acetoxy-benzylacetate, 69 222

t BuOH Et NOTos, 4-acetoxy-benzaldehyde, 8
4
Cu(OAc)2 4-acetoxy-benzaldehyde 3
diacetate
2 OH MeCN, AcOH (3 : 1) OH 75 223

MeO CHO NaOAc, NaClO4 MeO CHO
0.65 V
CH3 CH2OAc
3 OH MeCN, AcOH (3 : 1) OH 73 223

MeO CHO NaOAc, NaClO4 MeO CHO
0.8 V
CH3 CHO
4 p-Xylene CH3 OH, AcOH, NaBF4 86 226

CH3 CHO
5 p-Cresyl-acetate CH3 OH, AcOH, NaBF4 72 226

AcO CHO
6 p-Cresyl-t butyl ether MeOH, KF 80–85 227

tBuO CHO
step reaction to a corticoid with the Some of these processes have been
last step being a hydroboration/oxidation developed for technical conversions and
(Scheme 10) [224]. Oxidation of toluene have been summarized in Ref. [228,
in CH3 CN/LiClO4 with traces of water 229]. The anodic technical production
affords N -acetyl benzylamine in nearly of t-butylbenzaldehyde has been cou-
quantitatived yield [225]. pled with the cathodic reduction of
Oxidation of substituted toluenes to phthalic anhydride to phthalide in a
substituted benzaldehydes or their acetals paired electrosynthesis in a capillary
is a reaction that is of high technical gap cell [230]. Indirect oxidations with
interest. It is performed by direct as well Mn2+ /Mn3+ or Ce3+ /Ce4+ as mediators
as indirect anodic oxidation. A number are reported in [231–234]. With tris(2,4-
of direct oxidations is shown in Table 14, dibromophenyl)amine as mediator, dif-
Nr. 4 to 6. ferent substituted toluenes are converted
5.5 Comparison of Anodic Conversions of Alkanes, Alkenes, and Aromatic Compounds 161
CH2Cl2, NaClO4
MeOH,2,6-luti-
dine
MeO
(38)
O O
MeO
−CH3OH
MeO MeO
100% (39)
Scheme 10 Synthesis of a corticoid precursor (39) by anodic substitution.
in a 6e-oxidation in good yields to addition of methanol to 2-bromo-1,4-

trimethyl orthoesters of substituted ben- dimethoxybenzene (Table 15, number 3).
zoic acids [235]. Anodic oxidation of catechols leads to
reactive 1,2-quinones, which can be
5.4.3 trapped with 1,3-dicarbonyl compounds or
Anodic Addition dienes (Table 15, numbers 4,5).
The conversion to quinones is of tech-
nical interest (Vit. E, K) starting from
Aromatic compounds, substituted in 1,4-
phenol ethers or naphthalines (Table 15,
position with methoxy or hydroxy groups,
number 6) is compiled in Ref. [242]. For
undergo 1,4-addition with loss of the aro-
the oxidation to naphthoquinones, indirect
maticity (Eq. 21) (Table 15, numbers 1,2).
methods proved to be superior [243].
OMe MeO OMe

5.5
−e
Comparison of Anodic Conversions
MeOH, −H+
•
of Alkanes, Alkenes, and Aromatic
OMe OMe Compounds with their Chemical
Transformations
MeO OMe
−e Conversion of alkanes means substitution
of a hydrogen atom for a heteroatom. This
MeOH, −H+
is achieved at the anode by transfer of two
MeO OMe electrons from a C−H bond to the elec-
(21) trode and reaction of the intermediate car-
A synthon for an ‘‘umpoled’’ bocation with a nucleophile. Chemically in
quinone has been prepared by anodic most cases either a chlorine or bromine
Tab. 15 Anodic addition to aromatic compounds
Nr. Aromatic Compound X− or HX Product Yield [%] Ref.
1 Hydroquinone CH3 OH/KOH MeO OMe 75 236

dimethyl ether
MeO OMe
2 1,2,4-Trimeth- CH3 OH, KOH MeO OMe 91 237
oxybenzene OMe
MeO OMe
3 2-Bromo-1,4- MeOH, MeONa MeO OMe 75 238
dimeth- Br
oxybenzene
MeO OMe
4 Catechol cpe(1.1 V vs. OH 95 239
sce), aq. O
+
NaOAc
O O OH
O O
HO
5 OH CH3 NO2 , LiClO4 OH 92 240

HO 0.5%, HOAc O
CO2Et
+ EtO2C
Me
1,3-pentadiene
6 OCH3 CH3 OH, KF MeO OMe 77 241
MeO OMe
atom is introduced via a radical chain in one step, while the chemical version in
substitution. The halide is subsequently general needs two steps. On the other side,
exchanged for other nucleophiles in a SN 1 the regioselectivity is presently better to
or SN 2 reaction. The electrochemical re- control in chemical reactions and compet-
action has the advantage that oxygen and ing side reactions as C,C bond cleavage or
nitrogen groups can be introduced directly skeletal rearrangements are less frequent.
Conversion of alkenes comprehends metal-catalyzed selective heterocouplings,

dimerization, substitution, and addition. as the Kumada-, Heck- [246], Stille- and
Dehydrodimerization and additive dimer- Suzuki [247]-coupling, is described. Again
ization can be achieved at the anode with the higher selectivity in chemical versus
different sorts of alkenes in one step. electrochemical coupling has to be paid
Such reactions are rare in chemical conver- for by expensive catalysts or reagents and
sions and mostly multistep sequences are more reaction steps. Anodic oxidation of-
needed. Such couplings are, for example, fers a fairly large potential for oxidation of
the transition metal-catalyzed Heck- [244] the benzylic position to alcohols, ketones,
or metathesis-reaction [245]. They require aldehydes, and carboxylic acids and is in
mostly more reaction steps and expensive this respect superior to a chemical reac-
catalysts but lead to homo- and heterocou- tion also because selectivity plays a minor
pling with high selectivity. Substitutions role in these conversions. Anodic nuclear
of allylic hydrogen can be achieved at substitution allows the one-step introduc-
the anode with a fairly large variety of tion of the hydroxy, amino or cyano group,
heteroatom groups, as the halo, hydroxy, while in chemical nuclear substitution, the
oxo or amino group, in a one-pot reac- groups that can be directly introduced are
tion. Chemically, this is achieved mostly confined to the bromo, chloro, nitro, and
in a radical chain substitution of hy- sulfonyl group, while other substituents
drogen for chloride or bromide and a have to be introduced in multistep con-
subsequent nucleophilic substitution of versions. There the anode has a fairly
the halide against other heteroatoms. The large not yet fully exploited potential. Ad-
advantage of the anodic conversion is the dition reactions rely mainly on oxidations
one-pot conversion, while the chemical and are preferably done directly at the
transformations need several steps. This anode or mediated with a selective oxi-
is compensated frequently by a higher se- dant in catalytic amounts in an indirect
lectivity in the chemical reaction. Anodic electrolysis.
addition is a unique conversion because
it allows the addition of two nucleophiles References
to the double bond in one step. In chemi-
cal additions, mostly a nucleophile and an 1. T. Linker, M. Schmittel, Radikale und Rad-
electrophile are added. In anodic additions, ikalionen in der organischen Synthese, Wiley-
VCH, Weinheim, 1998.
however, the regio- and stereoselectivity 2. M. Schmittel, A. Burghart, Angew. Chem.
is often less developed than in chemi- 1997, 109, 2658–2699; Angew. Chem., Int.
cal additions. Ed. Engl. 1997, 36, 2550–2589.
The conversion of aromatic compounds 3. P. Renaud, M.P. Sibi, Radicals in Organic
comprises coupling, nuclear and ben- Synthesis, Wiley-VCH, Weinheim, 2001,
Vol. 1, 2.
zylic substitution, and in some cases, 4. M.B. Smith, J. March, Marchs’s Advanced
addition. Homo- and in a more lim- Organic Chemistry, Wiley Interscience, 5th
ited scope, heterocoupling is achieved for ed., New York, 2001, Chap. 5, 218–273.
unsubstituted and substituted aromatic 5. H. Siegermann in Technique of Electroor-
compounds in direct or indirect anodic ganic Synthesis, Part II (Ed.: N.L. Weinberg),
Wiley, New York, 1975, pp. 667–1056, there
processes. Chemically, there is a limited p. 676.
variety of expensive oxidation reagents 6. J. Perichon, M. Herlem, F. Bobilliart et al.
available, but a large scope of transition in Encyclopedia of Electrochemistry of the
Elements (Eds.: A.J. Bard, H. Lund), Marcel 27. J.Y. Becker, L.R. Byrd, L.L. Miller et al., J.
Dekker, New York, 1978, Vol. XI, pp. 5–42, Am. Chem. Soc. 1975, 97, 853–856.
there p. 7. 28. L.L. Miller, V. Ramachandran, J. Org. Chem.
7. J. Bertram, J.P. Coleman, M. Fleischmann 1974, 39, 369–372.
et al., J. Chem. Soc., Perkin Trans. 2 1973, 29. T.M. Siegel, L.L. Miller, J. Chem. Soc.,
374–381. Chem. Commun. 1974, 341–342.
8. J.P. Coleman, D. Pletcher, J. Electroanal. 30. T. Shono, Y. Matsumura, Y. Nakagawa, J.
Chem. 1978, 87, 111–117. Org. Chem. 1971, 36, 1771–1775.
9. Ch. Pitti, M. Cerles, A. Thiebault et al., J. 31. T. Shono, Y. Matsumura, Bull. Chem. Soc.
Electroanal. Chem. 1981, 126, 163–174. Jpn. 1975, 48, 2861–2864.
10. S. Pitti, M. Herlem, J. Jordan, Tetrahedron 32. M. Klehr, H.J. Schäfer, Angew. Chem. 1975,
Lett. 1976, 3221–3224. 87, 173–174; Angew. Chem., Int. Ed. Engl.
11. J.P. Coleman, J. Electrochem. Soc. 1981, 128, 1975, 14, 247–248.
2561–2565. 33. S. Torii, T. Okomoto, N. Ueno, J. Chem.
12. P. Sartori, N. Ignat’ev, J. Fluorine Chem. Soc., Chem. Commun. 1978, 293–294.
1998, 87, 157–162. 34. S. Torii, T. Inokuchi, N. Takahashi, J. Org.
13. F.G. Drakesmith, Top. Curr. Chem. 1997, Chem. 1978, 43, 5020–5022.
193, 197–242. 35. A.J. Baggaley, R. Brettle, J.R. Sutton,
14. Y.W. Alsmeyer, W.V. Childs, R.M. Flynn J. Chem. Soc., Perkin Trans. 1 1975,
et al., Organofluorine Chem. 1994, 121–143. 1055–1059.
15. W.V. Childs, L. Christensen, F.W. Klink 36. T. Uchida, Y. Matsubara, I. Nishiguchi et al.,
et al. in Organic Electrochemistry, 3rd J. Org. Chem. 1990, 55, 2938–2943.
ed. (Eds.: H. Lund, M.M. Baizer), Marcel 37. R. Tomat, A. Rigo, J. Appl. Electrochem.
1986, 16, 8–14.
Dekker, New York, 1991, pp. 1103–1127,
38. I. Nishiguchi, R. Shundou, A. Ikeda et al.,
Chap. 26.
2nd International IUPAC Symposium of Or-
16. H.J. Schäfer, E. Cramer, A. Hembrock et al.
ganic Chemistry: Technological Perspectives,
in Electroorganic Synthesis (Eds.: R.D. Little,
Baden-Baden, FRG, 14.-19.4.91, Poster 54.
N.L. Weinberg), Marcel Dekker, New York,
39. R.J. Gorte, S. Park, J.M. Vohs et al., Adv.
1991, pp. 169–180.
Mater. 2000, 12, 1465–1469.
17. H.P. Fritz, T. Würminghausen, Z. Natur-
40. S. Park, J.M. Vohs, R.J. Gorte, Nature 2000,
forsch. B 1977, 32, 241–248. 404(6775), 265–267.
18. A. Hembrock, H.J. Schäfer, Angew. Chem. 41. T.I. Mazanec, T.L. Cable, UK Pat. 2203446
1985, 97, 1048–1049; Angew. Chem., Int. A; Chem. Abstr. 1989, 110, 135899k.
Ed. Engl. 24, 1985, 1055–1056. 42. A. Kühnle, G. Stochniol, M. Duda, DE 198
19. A. Hembrock, H.J. Schäfer in Proceeding of 41 872 A1 (2000); Chem. Abstr. 2000, 132,
the 1st International Symposium on Elec- 200309.
troorganic Synthesis (Ed.: S.Torii), Kodansha, 43. K. Otsuka, A. Morikawa, Jap. Pat. 61030688
Tokyo, 1987, pp. 121–124. A2; Chem. Abstr. 1986, 105, 114383u.
20. D.B. Clark, M. Fleischmann, D. Pletcher, 44. K. Otsuka, K. Suga, I. Yamanaka, Catal.
J. Chem. Soc., Perkin Trans. 2 1973, Today, 1990, 6, 587; Chem. Abstr. 1990, 113,
1578–1581. 118105t.
21. V.R. Koch, L.L. Miller, Tetrahedron Lett. 45. N.U. Pujare, A.F. Sammells, J. Electrochem.
1973, 693–696. Soc. 1988, 135, 2544–2545.
22. V.R. Koch, L.L. Miller, J. Am. Chem. Soc. 46. T.I. Mazanec, T.L. Cable, US Pat. 4802958
1973, 95, 8631–8637. A; Chem. Abstr. 1989, 110, 215208z.
23. G.J. Edwards, S.R. Jones, J.M. Mellor, J. 47. Ref. [6], there pp. 17–23.
Chem. Soc., Chem. Commun. 1975, 816–817. 48. J. Volke, F. Liska, Electrochemistry in Organic
24. S.R. Jones, J.M. Mellor, J. Chem. Soc., Chem. Synthesis, Springer-Verlag, Berlin a.o., 1994,
Commun. 1976, 385–386. p. 48.
25. G.J. Edwards, S.R. Jones, J.M. Mellor, J. 49. B. Aalstad, A. Ronlan, V.D. Parker, Acta
Chem. Soc., Perkin Trans. 2 1977, 505–510. Chem. Scand. 1981, B35, 247–257.
26. J.Y. Becker, L.R. Byrd, L.L. Miller, J. Am. 50. E. Steckhan, J. Am. Chem. Soc. 1978, 100,
Chem. Soc. 1974, 96, 4718–4719. 3526–3533.
51. G. Burgbacher, H.J. Schäfer, J. Am. Chem. 75. R.D. Little, K.D. Moeller, Electrochem. Inter-
Soc. 1979, 101, 7590–7593. face 2002, 11, 36–42.
52. R. Engels, H.J. Schäfer, E. Steckhan, Liebigs 76. H.J. Schäfer in Organic Electrochemistry,
Ann. Chem. 1977, 204–224. 4th ed. (Eds.: H. Lund, O. Hammerich),
53. E. Steckhan, H. Schäfer, Angew. Chem. Marcel Dekker, New York, 2001, Chap. 22,
1974, 86, 480–481; Angew. Chem., Int. Ed. 883–967.
Engl. 1974, 13, 472–473. 77. K.C. Möller, H.J. Schäfer, Electrochim. Acta
54. H. Sternerup, Acta Chem. Scand. 1974, B28, 1997, 42, 1971–1978.
579–585. 78. T. Shono, A. Ikeda, J. Am. Chem. Soc. 1972,
55. H. Schäfer, E. Steckhan, Angew. Chem. 94, 7892–7898.
1969, 81, 532; Angew. Chem., Int. Ed. Engl. 79. A. Bewick, J.M. Mellor, S.B. Pons, J. Chem.
1969, 8, 518. Soc., Chem. Commun. 1978, 738.
56. B. Belleau, Y.K. Au-Young, Can. J. Chem. 80. T. Shono, A. Ikeda, Y. Kimura, Tetrahedron
1969, 47, 2117–2118. Lett. 1971, 3599–3692.
57. M.A. Le Moing, G. Le Guillanton, J. Simo- 81. T. Shono, M. Okawa, I. Nishiguchi, J. Am.
net, Electrochim. Acta 1981, 26, 139–144. Chem. Soc. 1975, 97, 6144–6147.
58. D. Koch, H. Schäfer, E. Steckhan, Chem. 82. S. Torii, K. Uneyama, T. Nakai et al., Tetra-
Ber. 1974, 107, 3640–3657. hedron Lett. 1981, 22, 2291–2294.
59. R. Engels, Ph. D. thesis, University of 83. A. Guirado, G.P. Moss, J.H.P. Utley, J.
Münster, Münster, 1978. Chem. Soc., Chem. Commun. 1987, 41–42.
60. J.M. Fritsch, H. Weingarten, J. Am. Chem. 84. T. Shono, A. Ikeda, J. Hayashi et al., J. Am.
Soc. 1968, 90, 793–795. Chem. Soc. 1975, 97, 4261–4264.
61. J.M. Fritsch, H. Weingarten, J.D. Wilson, J. 85. T. Shono, Y. Matsumura, H. Hamaguchi
Am. Chem. Soc. 1970, 92, 4038–4046. et al., Bull. Chem. Soc. Jpn. 1978, 51,
62. D. Koch, H.J. Schäfer, Angew. Chem. 1973, 2179–2180.
85, 264–265; Angew. Chem., Int. Ed. Engl. 86. T. Shono, A. Ikeda, Chem. Lett. 1976,
1973, 12, 254–255. 311–314.
63. H.W. Handiak, Ph. D. thesis, University of 87. T. Shono, I. Nishiguchi, M. Okawa, Chem.
Göttingen, Göttingen, 1976. Lett. 1976, 573–576.
64. N. Dahrenmöller, Masters thesis, Univer- 88. C. Adams, N. Jacobsen, J.H.P. Utley,
sity of Münster, Münster, 1976. J. Chem. Soc., Perkin Trans. 2 1978,
65. H. Baltes, E. Steckhan, H.J. Schäfer, Chem. 1071–1076.
Ber. 1978, 111, 1294–1314. 89. F.M. Banda, R. Brettle, J. Chem. Soc., Perkin
66. M. Katz, O. Saygin, H. Wendt, Electrochim. Trans. 1 1974, 1907–1908.
Acta. 1974, 19, 193–200. 90. H. Baltes, L. Stork, H.J. Schäfer, Angew.
67. K. Nehring, H.J. Schäfer, University of Chem. 1977, 89, 425; Angew. Chem., Int.
Göttingen, Göttingen, 1974: unpublished Ed. Engl. 1977, 16, 413.
results. 91. N. Klauson-Kaas, F. Limborg, K. Glens,
68. H. Schäfer, E. Steckhan, Tetrahedron Lett. Acta Chem. Scand. 1952, 6, 531–534.
1970, 3835–3838. 92. DE 2710420, BASF, D. Degner, H. Han-
69. K.D. Moeller, Top. Curr. Chem 1997, 185, nebaum, H. Nohe, Chem. Abstr. 1979, 90,
49–86, there p. 76. 94451f.
70. D.A. Fry, S.H. Reddy, K.D. Moeller, J. Org. 93. S. Torii, T. Yamanaka, H. Tanaka, J. Org.
Chem. 1999, 64, 2805–2813, there refer- Chem. 1987, 43, 2882–2885.
ences to earlier work. 94. H.J. Schäfer in Radicals in Organic Synthesis
71. D.A. Fry, N. Wu, K.D. Moeller, Tetrahedron (Eds.: P. Renaud, M.P. Sibi), Wiley-VCH,
Lett. 1996, 37, 8317–8320. Weinheim, 2001, pp. 250–297, Chap. 2.6.
72. T. Shono, I. Nishigushi, S. Kashimura et al., 95. H. Schäfer, A. Al Azrak, Chem. Ber. 1972,
Bull. Chem. Soc. Jpn. 1978, 51, 2181–2182. 105, 2398–2418.
73. J.S. Swenton, K. Carpenter, Y. Chen et al. J. 96. J. Yoshida, K. Sakaguchi, S. Isoe, J. Org.
Org. Chem. 1993, 58, 3308–3316. Chem. 1988, 53, 2525–2533.
74. J.S. Swenton, A. Calliman, Y. Chen et al., J. 97. T. Chiba, M. Okimoto, H. Nagai et al., J.
Org. Chem. 1996, 61, 1267–1274. Org. Chem. 1979, 44, 3519–3523.
98. R. Shundo, I. Nishiguchi, Y. Matsubara 121. G. Dralle, Ph.D. thesis, University of

et al., Tetrahedron 1991, 47, 831–840. Münster (FRG), Münster, 1990.
99. F. Bergamini, A. Citterio, N. Gatti et al., J. 122. Ref. [94], there pp. 280–281.
Chem. Res. (S) 1993, 364–365. 123. A. Matzeit, H.J. Schäfer, C. Amatore, Syn-
100. H. Schäfer, Habilitation thesis, University thesis 1995, 1432–1444.
of Göttingen (FRG), Göttingen, 1970. 124. B. Giese, B. Kopping, T. Göbel et al., Org.
101. H. Schäfer, H. Küntzel, Tetrahedron Lett. React. 1996, 48, 301–856.
1970, 3333–3336. 125. D.P. Curran in Comprehensive Organic Syn-
102. H. Schäfer, R. Pistorius, Angew. Chem. thesis (Ed.: B.M. Trost), Pergamon Press,
1972, 84, 893–894; Angew. Chem., Int. Ed. Oxford, 1991, pp. 715–777, Vol. 4.
Engl. 1972, 11, 841–842. 126. E. Steckhan, Top. Curr. Chem. 1987, 142,
103. Y.B. Vasilev, L.S. Kanevskii, K.G. Kara- 1–69.
petyan et al., Elektrokhimiya 1978, 14, 127. S. Torii, Electroorganic Syntheses, Part I Oxi-
770–773; Chem. Abstr. 1978, 89, 119649. dation, Kodansha-VCH, Tokyo, Weinheim,
104. M.Y. Fioshin, L.A. Salmin, L.A. Mirkind 1985, Chap. 11, 279–306.
et al., Zh. Obshch. Khim. 1965, 10, 594–595; 128. J. Simonet, J.F. Pilard in Organic Electro-
Chem. Abstr. 1966, 64, 10 986. chemistry (Eds.: H. Lund, O. Hammerich),
105. C.J. Brookes, P.L. Coe, D.M. Owen et al., J. Marcel Dekker, New York, 2001, Chap. 29,
Chem. Soc., Chem. Commun. 1974, 323–324. 1163–1225.
106. M. Chkir, D. Lelandais, J. Chem. Soc., Chem. 129. E. Steckhan in Organic Electrochemistry
Commun. 1971, 1369–1370. (Eds.: H. Lund, O. Hammerich), Mar-
107. K.G. Karapetyan, A.A. Bezzubov, L.S. Kane- cel Dekker, New York, 2001, Chap. 27,
vskii et al., Elektrokhimiya 1976, 12, 1623; 1103–1146.
Chem. Abstr. 1977, 86, 62 705.
130. A. Ledwith, Acc. Chem. Res. 1972, 5,
108. R.N. Renaud, P.J. Champagne, M. Savard,
133–139.
Can. J. Chem. 1979, 57, 2617–2620.
131. L. Cedheim, L. Eberson, Acta Chem. Scand.
109. P.J. Champagne, R.N. Renaud, Can. J.
B30, 1976, 527–532.
Chem. 1980, 58, 1101–1105.
132. J. Delaunay, A.O. -LeMoing, J. Simonet
110. M. Huhtasaari, H.J. Schäfer, L. Becking,
et al., Tetrahedron Lett. 1986, 27, 6205–6208.
Angew. Chem. 1984, 96, 995–996; Angew.
133. J. Mlcoch, E. Steckhan, Tetrahedron Lett.
Chem., Int. Ed. Engl. 1984, 23, 980–981.
111. L. Feldhues, H.J. Schäfer, Tetrahedron Lett. 1987, 28, 1081–1084.
1988, 29, 2797–2800. 134. K. Chiba, T. Miura, K. Shokaku et al., J. Am.
112. J.P. Coleman, R.C. Hallcher, D.E. McMack- Chem. Soc. 2001, 123, 11 314–11 315.
ins et al., Tetrahedron 1991, 47, 809–829. 135. I. Tabakovic, Z. Grujic, Z. Bejtovic, J. Hete-
113. H. Schäfer, D. Koch, Angew. Chem. 1972, rocycl. Chem. 1983, 20, 635–638.
84, 32–33; Angew. Chem., Int. Ed. Engl. 1972, 136. K. Chiba, M. Jinno, A. Nozaki et al., J. Chem.
11, 48–49. Soc., Chem. Commun. 1997, 1403–1404.
114. H. Schäfer, Angew. Chem. 1970, 82, 137. S. Yamamura in Novel Trends in Electroor-
134–135; Angew. Chem., Int. Ed. Engl. 1970, ganic Synthesis (Ed.: S. Torii), Kodansha,
9, 158–159. Tokyo, 1995, pp. 265–268.
115. T. Shono, M. Chauankamnerdkarn, H. Ma- 138. S. Yamamura in Novel Trends in Electroor-
ekawa et al., Synthesis 1994, 895–897. ganic Synthesis (Ed.: S. Torii), Springer,
116. T. Shono, T. Soejima, K. Takigawa et al., Tokyo, 1998, pp. 19–22.
Tetrahedron Lett. 1994, 35, 4161–4164. 139. K.D. Moeller, Top. Curr. Chem. 1997, 185,
117. K. Uneyama, Tetrahedron 1991, 47, 49–86, there p. 66.
555–562. 140. H. Siegermann in Technique of Electroor-
118. V. Plzak, H. Wendt, H. Schneider, ganic Synthesis, Part II, in Techniques of
Ber. Bunsen-Ges. Phys. Chem. 1974, 78, Chemistry (Ed.: N. Weinberg), John Wiley,
1373–1379. New York, 1975, Vol. 5, pp. 667–1065.
119. L. Feldhues, H.J. Schäfer, Tetrahedron Lett. 141. K. Nyberg in Encyclopedia of Electrochemistry
1988, 29, 2801–2802. of the Elements (Eds.: A. Bard, H. Lund),
120. J. Weiguny, H.J. Schäfer, Liebigs Ann. Marcel Dekker, New York, 1978, Vol. XI,
Chem. 1994, 235–242. pp. 43–70.
142. J. Perichon in Encyclopedia of Electrochem- 166. L. Eberson, B. Helgee, Acta Chem. Scand.
istry of the Elements (Eds.: A. Bard, H. Lund), 1977, B31, 813–817.
Marcel Dekker, New York 1978, Vol. XI, 167. M.T. Ismail, M.F. El-Zohry, A.A. Abdel Wa-
pp. 71–161. hab, J. Appl. Electrochem. 1985, 15, 469–470;
143. Ref. [141], there pp. 60–61. Chem. Abstr. 1985, 103, 44 765.
144. J. Grimshaw, Electrochemical Reactions and 168. A.I. Scott, Q. Rev. Biophys. 1965, 19, 1–35;
Mechanisms in Organic Chemistry, Elesevier, T. Kametani, K. Fukomoto, Synthesis 1972,
Amsterdam, 2000, Chap. 6, pp. 187–238. 657–674.
145. O. Hammerich in Organic Electrochemistry, 169. H. Lund in The Chemistry of the Hydroxyl
4th ed. (Eds.: H. Lund, O. Hammerich), Group (Ed.: S. Patai), Wiley, New York,
Marcel Dekker, New York, 2001, Chap. 13, 1971, Vol. 1, Chap. 5; A. Ronlan in Ency-
pp. 471–498. clopedia of Electrochemistry of the Elements
146. J.H.P. Utley, G.G. Rozenberg, Tetrahedron (Eds.: A.J. Bard, H. Lund), Marcel Dekker,
2002, 58, 5251–5265. New York, 1978, pp. 242–275, Vol. 11.
147. L. Eberson, K. Nyberg, H. Sternerup, Acta 170. H.J. Schäfer in Organic Electrochemistry,
Chem. Scand. 1973, 27, 1679–1683. 4th ed. (Eds.: H. Lund, O. Hammerich),
148. K. Nyberg, Acta Chem. Scand. 1971, 25, Marcel Dekker, New York, 2001, Chap. 22,
2499–2506. pp. 883–967.
149. K. Nyberg, Acta Chem. Scand. 1971, 25, 171. F. Fichter, F. Ackerman, Helv. Chim. Acta
534–542. 1919, 2, 583–599.
150. K. Nyberg, Acta Chem. Scand. 1971, 25, 172. K. Sasaki, S. Nanao, A. Kunai, Denki Ka-
2983–2988. gaku 1977, 45, 130–135; Chem. Abstr. 1977,
151. H. Millauer, DE 4342282, Hoechst 1995; 87, 134 212.
173. S. Torii, A.-L. Dhimane, Y. Araki et al.,
Chem. Abstr. 1995, 123, 82 965.
Tetrahedron Lett. 1989, 30, 2105–2108
152. V.D. Parker, Acta Chem. Scand. 1970, 24,
174. H. Ohmori, A. Matsumoto, M. Masui et al.,
3162–3170.
J. Electrochem. Soc. 1977, 124, 1849–1854.
153. V.D. Parker, Acta Chem. Scand. 1970, 24,
175. J.M. Bobbitt, I. Noguchi, H. Yagi et al., J.
3171–3177.
Org. Chem. 1976, 41, 845–850.
154. A.E. Coleman, H.H. Richtol, D.A. Aikens,
176. K.M. Johnston, Tetrahedron Lett. 1967,
J. Electroanal. Chem. 1968, 18, 165–174.
837–839.
155. K. Nyberg, Acta Chem. Scand. 1971, 25, 177. A. Rieker, H.P. Schneider, E. Streich in Re-
3770–3776. cent Advances in Electroorganic Synthesis (Ed.:
156. K. Nyberg, Acta Chem. Scand. 1973, 27, S. Torii), Kadansha, Elsevier, Amsterdam,
503–509. 1987, pp. 57–60.
157. K. Nyberg, A. Trojanek, Coll. Czech. Chem. 178. M. Iguchi, A. Nishiyama, Y. Terada et al.,
Commun. 1975, 40, 526–532. Chem. Lett. 1978, 451–454.
158. U. Svanholm, V.D. Parker, J. Am. Chem. 179. F.J. Vermillion Jr, I.A. Pearl, J. Electrochem.
Soc. 1976, 98, 2942–2946. Soc. 1964, 111, 1392–1400.
159. A. Bewick, G.J. Edwards, J.M. Mellor et al., 180. V.D. Parker in Encyclopedia of Electro-
J. Chem. Soc., Perkin Trans. 2 1977, chemistry of the Elements (Eds.: A.J. Bard,
1952–1958. H. Lund), Marcel Dekker, New York, 1978,
160. R.N. Adams, Acc. Chem. Res. 1969, 2, Vol. 11, pp. 276–315.
175–180. 181. A. Ronlán, K. Bechgaard, V.D. Parker, Acta
161. O. Hammerich, V.D. Parker, Adv. Phys. Chem. Scand. 1973, 27, 2375–2382.
Org. Chem. 1984, 20, 55–189. 182. O. Hammerich, V.D. Parker, Electrochim.
162. O. Hammerich, V.D. Parker, J. Am. Chem. Acta 1973, 18, 537–541.
Soc. 1974, 96, 4289–4296. 183. H.G.H. Erdtman, Proc. R. Soc. London 1933,
163. U. Svanholm, V.D. Parker, J. Am. Chem. 143A, 191–222; Chem. Abstr. 1933, 28,
Soc. 1976, 98, 2942–2946. 11 102.
164. J.M. Bobbitt, J.P. Willis, J. Org. Chem. 42, 184. V.D. Parker, R.N. Adams, Tetrahedron Lett.
1977, 2347–2348. 1969, 1721–1724.
165. S. Andreades, E.W. Zahnow, J. Am. Chem. 185. O. Hammerich, V.D. Parker, Acta Chem.
Soc. 1969, 91, 4181–4190. Scand. 1982, B36, 519–527.
186. R.F. Stewart, L.L. Miller, J. Am. Chem. Soc. 210. L. Eberson, E. Oberrauch, Acta Chem.
1980, 102, 4999–5004. Scand. 1981, B35, 193–196.
187. K. Beechgard, V.D. Parker, J. Am. Chem. 211. Y.H. So, J.Y. Becker, L.L. Miller, J. Chem.
Soc. 1972, 94, 4749–4750. Soc., Chem. Commun. 1975, 262–263.
188. L. Le Berre, L. Angély, N. Simonet-Gueguen 212. R.S. Glass, V.V. Jouikov, N.V. Bojkova, Proc.
et al., J. Chem. Soc., Chem. Commun. 1987, Electrochem. Soc. 2000, 5–8.
984–986. 213. B. Fabre, F. Kanoufi, J. Simonet, J. Elec-
189. J.-M. Chapuzet, J. Simonet, Tetrahedron troanal. Chem. 1997, 434, 225–234.
1991, 47, 791–798; J.-M. Chapuzet, J. Simo- 214. K. Yoshida, S. Nagase, J. Am. Chem. Soc.
net, Tetrahedron Lett. 1991, 32, 7405–7408. 1979, 101, 4268–4272.
190. S.R. Waldvogel, D. Mirk, Tetrahedron Lett. 215. Y.H. Su, J. Org. Chem. 1985, 80, 5895–5896.
2000, 41, 4769–4772. 216. T. Shono, Y. Matsumura, S. Katoh et al.,
191. L. Eberson, J. Am. Chem. Soc. 1967, 89, Tetrahedron Lett. 1989, 30, 1649–1650.
4669–4677. 217. M.J. Peacock, D. Pletcher, Tetrahedron Lett.
192. L. Eberson, K. Nyberg, Acta Chem. Scand. 2000, 41, 8995–8998.
B, 1975, 29, 168–170. 218. M.J. Peacock, D. Pletcher, J. Electrochem.
193. G. Bockmair, H.P. Fritz, Electrochim. Acta Soc. 2001, 148, D37–D42.
1976, 21, 1099–1100. 219. I. Gallardo, G. Guirado, J. Marquet, J. Org.
194. D. Degner, Top. Curr. Chem. 1988, 148, Chem. 2003, 68, 631–633.
1–95, there p. 12–15 also with further 220. I. Gallardo, G. Guirado, J. Marquet, Eur. J.
similar conversions. Org. Chem. 2002, 261–267.
195. L. Eberson, B. Helgee, Acta Chem. Scand. 221. D. Degner, Top. Curr. Chem. 1988, 148,
1978, B32, 157–161. 1–95, there p. 18–19.
196. L. Eberson, K. Nyberg, J. Am. Chem. Soc. 222. S. Torii, H. Tanaka, T. Inokuchi et al., J.
1966, 88, 1686–1691. Org. Chem. 1982, 47, 1647–1652.
197. D. Degner, Top. Curr. Chem. 1988, 1–95, 223. H. Ohmori, A. Matsumoto, M. Masui et al.,
there p. 15. J. Electrochem. Soc. 1977, 124, 1849–1854.
198. Z. Blum, L. Cedheim, K. Nyberg et al., Acta 224. K. Ponsold, H. Kasch, Tetrahedron Lett.
Chem. Scand. 1975, B29, 715–718. 1979, 4463–4464.
199. O. Hammerich, V.D. Parker, Acta Chem. 225. V.D. Parker, B.E. Burgert, Tetrahedron Lett.
Scand. 1982, B36, 519–527. 1968, 2411–2414.
200. L. Eberson, B. Helgee, Chem. Scr. 1974, 5, 226. I. Nishiguchi, T. Hirashima, J. Org. Chem.
47; Chem. Abstr. 1974, 80, 82 473. 1985, 50, 539–541.
201. L. Eberson, B. Helgee, Acta Chem. Scand. B 227. DE 2 935 398, BASF, M. Barl, D. Degner,
1975, 29, 451–456. H. Siegel et al., Chem. Abstr. 1981, 95,
202. DE 2 309 127, Rhone-Poulenc, J. Bizot, 24 556y.
J. Courteix, J.P. Phillipot, Chem. Abstr. 1973, 228. D. Degner, Top. Curr. Chem. 1988, 148,
97, 142 367e. 1–95, there p. 20–22.
203. I.N. Rozhkov, I.Y. Alyev, Tetrahedron 1975, 229. H. Pütter in Organic Electrochemistry, 4th
31, 977–981. ed. (Eds.: H. Lund, O. Hammerich), Mar-
204. DE 3 319 795, Hoechst, W. Farnung; Chem. cel Dekker, New York, 2001, Chap. 31,
Abstr. 1985, 102, 86 470n. pp. 1259–1307.
205. I. Gallardo, G. Guirado, J. Marquet, Eur. J. 230. H. Pütter, Innovation Award 1999, BASF.
Org. Chem. 2002, 251–259. 231. D. Degner, Top. Curr. Chem. 1988, 148,
206. V.L. Pardini, S.K. Sakata, R.R. Vargas et al., 1–95, there p. 22.
J. Braz. Chem. Sol. 2001, 12, 223–229. 232. H. Pütter in Organic Electrochemistry, 4th
207. EP 919533, Hydro-Quebec, S. Harrison, ed. (Eds.: H. Lund, O. Hammerich), Mar-
G. Fiset, B. Mahdavi, Chem. Abstr. 1999, cel Dekker, New York, 2001, Chap. 31,
131, 511. 1259–1307, there p. 1288.
208. Y.H. So, L.L. Miller, Synthesis 1976, 233. T. Tzedakis, A. Savall, J. Appl. Electrochem.
468–469. 1997, 27, 589–597.
209. G. Bockmair, H.P. Fritz, H. Gebauer, Elec- 234. WO 9318208, Hydro-Quebec, S. Harrison,
trochim. Acta 1978, 23, 21–23. Chem. Abstr. 1993, 120, 119 439.
235. K.H. Grosse Brinkhaus, E. Steckhan, 243. H. Pütter in Organic Electrochemistry, 4th
D. Degner, Tetrahedron 1986, 42, 553–560. ed. (Eds.: H. Lund, O. Hammerich), Mar-
236. N.L. Weinberg, B. Belleau, Tetrahedron cel Dekker, New York, 2001, Chap. 31,
1973, 29, 279–285. 1259–1307, there p. 1293.
237. D.A. Evans, S.P. Tanis, D.J. Hart, J. Am. 244. S. Braese, A. De Meijere in Handbook
Chem. Soc. 1981, 103, 5813–5821. of Organopalladium Chemistry for Or-
238. M.J. Manning, P.W. Raynolds, J.S. Swen- ganic Synthesis, Wiley-VCH, 2002, Vol. 1,
ton, J. Am. Chem. Soc. 1976, 98, 5008–5009. pp. 1369–1403.
239. Z. Grujic, I. Tabakovic, M. Trkovnik, Tetra- 245. A. Fuerstner, Angew. Chem., Int. Ed. Engl.
hedron Lett. 1976, 4823–4824. 2000, 39, 3012–3043.
240. K. Chiba, M. Tada, J. Chem. Soc., Chem. 246. Ch.E. Tucker, J.G. De Vries, Top. Catal.
Commun. 1994, 2485–2486. 2002, 19, 111–118.
241. EP 53 261, BASF, D. Degner, M. Barl, 247. R. Franzen, Can. J. Chem. 2000, 78,
Chem. Abstr. 1982, 97, 117454. 957–962.
242. D. Degner, Top. Curr. Chem. 1988, 148,
there p. 13–15.
171
6
Oxidation of Oxygen-containing
Compounds (Alcohols, Carbonyl
Compounds, Carboxylic Acids)
Yoshihiro Matsumura
Department of Pharmaceutical Sciences, Graduate School of Biomedical
Sciences, Nagasaki University, Japan
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
6.2 Oxidation of Alcohols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173

6.2.1 Direct Oxidation of Alcohols . . . . . . . . . . . . . . . . . . . . . . . . . . . 174
6.2.1.1 Aliphatic Alcohols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174
6.2.2 Indirect Oxidation of Alcohols . . . . . . . . . . . . . . . . . . . . . . . . . . 175
6.2.2.1 Mediators Fixed to the Electrode Surface . . . . . . . . . . . . . . . . . . . 176
6.2.2.2 Mediators Dissolved in the Electrolyte . . . . . . . . . . . . . . . . . . . . . 177
6.2.2.2.1 Metal Ion Mediators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
6.2.2.2.2 Halide Ion Mediators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
6.2.2.2.3 Organic Mediators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
6.3 Oxidation of Phenols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180

6.3.1 Oxidation of Phenols to Quinones . . . . . . . . . . . . . . . . . . . . . . . 180
6.3.2 C, C−Bond Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
6.4 Oxidation of Carbonyl Compounds . . . . . . . . . . . . . . . . . . . . . . . 182

6.4.1 Direct Oxidation of Carbonyl Compounds . . . . . . . . . . . . . . . . . . 183
6.4.2 Indirect Oxidation of Carbonyl Compounds . . . . . . . . . . . . . . . . . 184
6.5 Oxidation of Carboxylic Acids . . . . . . . . . . . . . . . . . . . . . . . . . . 185

6.5.1 The Kolbe Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
6.5.2 The Non-Kolbe Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
6.5.2.1 Reaction with Nucleophiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
6.5.2.2 Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
6.5.2.3 Olefin Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
6.5.2.4 Oxidative Decarboxylation of α-heteroatom-substituted Carboxylic
Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
172 6 Oxidation of Oxygen-containing Compounds (Alcohols, Carbonyl Compounds, Carboxylic Acids)
6.5.3 Oxidation of Amides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
173
6.1 the direct method, though there have

Introduction been exceptions.
Both direct and indirect anodic oxidation
The anode is an ideal reagent to oxi- have a variety of advantages over chemical
dize organic substrates such as oxygen- oxidation methods.
containing compounds (alcohols, car- This article shows a variety of patterns
bonyl compounds, and carboxylic acids). of electrochemical oxidation of oxygen-
Thereby these substrates can be converted containing compounds (alcohols, carbonyl
avoiding chemical reagents, which sim- compounds, and carboxylic acids), aiming
plifies the reaction conditions and the to be helpful for both electroorganic
work-up. Additionally, the electron trans- and organic chemists to cover this field
fer leads selectively to a variety of reactive from a synthetic viewpoint. Since there
species, which can find further use in or- have been excellent books [1–5] published
ganic synthesis. on the subject, this article quotes only
The reactions can be classified into two some typical and important papers from
categories, direct and indirect oxidation before 1990.
methods, which are schematically repre-
sented in Figs. 1 and 2.
In the direct method substrates are 6.2
oxidized by electron transfer from the Oxidation of Alcohols
substrate to the anode, while in the indirect
method they are oxidized in solution by Direct electrochemical oxidation is not
the oxidized form of a mediator that is a convenient way for a preparative pro-
generated from the reduced form at the duction of carbonyl compounds from
anode. Thus, efficiencies in direct and alcohols due to the unselectivity caused
indirect methods are largely dependent on by the high oxidation potentials of al-
the oxidation potentials of substrates and cohols. Thus, there have been only a
mediators, respectively. few compounds (some aliphatic alco-
Since alcohols and ketones generally hols, glycols, and related alcohols) that
possess high oxidation potentials, the have been oxidized by the direct method,
indirect method is often applied to while the indirect method has often
those compounds, while phenols and been used to oxidize selectively a va-
carboxylic acids are mainly oxidized by riety of alcohols, since it does not
Fig. 1 Direct
oxidation method.
Substrate
Product e
Anode
Fig. 2 Indirect
oxidation method.
Substrate [Mediator]+ e
Product Mediator
Anode
depend on the oxidation potentials of Another recently reported example is

the substrates. the electrochemical oxidation of 2,2,2-
trifluoroethanol (3) to trifluoroacetalde-
6.2.1 hyde 2,2,2-trifluoroethyl hemiacetal (4),
Direct Oxidation of Alcohols which can be used as an equivalent of tri-
fluoroacetaldehyde (Eq. 2) [8]. The yield of
6.2.1.1 Aliphatic Alcohols (4) was 70 to 75% at a current consumption
The direct electrochemical oxidation of of 1.5 F mol−1 .
aliphatic alcohols (1) to carbonyl com-
OH
pounds (2) (Eq. 1) is not a convenient −2e
CF3CH2OH Et NBF CF3
way for synthesis because of the high 4 4 (2)
OCH2CF3
oxidation potentials of alcohols. The oxi- (3) (4)
dation always competes with the oxidation
of a solvent and supporting electrolyte, Higher alcohols, however, cannot be
leading to low current efficiencies and used as neat liquids in electrolysis. For
side products. anodic oxidation those alcohols must be
dissolved in appropriate solvents. Acetoni-
R1 −2e R1 trile is the most frequently used solvent
OH −2H+ O for that purpose. Electrochemical oxida-
(1)
R2 R2
tion of n-butyl alcohol to n-butyraldehyde
(1) (2)
was achieved in moderately dilute acetoni-
Although the lower alcohol homologues trile solution in a current yield of 77% [9].
such as MeOH and EtOH can be ox- The oxidation of alkoxides instead of
idized electrochemically in aqueous so- alcohols is an alternative to achieve the
lution, the mechanism is complex and desired oxidation. A spiro-cyclization of
barely investigated [6]. Electrolysis of the (5) occurred, when it was electrolyzed
neat liquid is one way to achieve the di- in EtOH containing both EtONa and
rect oxidation of MeOH and EtOH [7]. LiBF4 to afford 61% of the spiroacetal (6)
6.2 Oxidation of Alcohols 175
−2e
−2H+
O
EtOH
C6H13 O OH NaOEt C6H13 O
LiBF4
(5) (6) 61%
Scheme 1 Anodic conversion of ether to ketal.
(Scheme 1) [10]. The choice of solvent and Benzyl alcohols: Aryl alkyl carbinols (11)
supporting electrolyte was important for can be oxidized to ketones (12) by
the selectivity. the direct electrochemical method (Eq. 4)
Alcohols with ring strain can be oxidized since they possess their oxidation poten-
by the direct method. Borneol (7) was tials at around 2.0 V versus SCE (satu-
electrochemically oxidized in MeOH with rated calomel electrode); however, cleavage
cleavage of the Cα –Cβ bond to afford (8) products decrease the selectivity [14].
with an endo/exo ratio of 97/3 in more than
OH −2e
70% yield at 5 F mol−1 (Scheme 2) [11]. O
MeCN
Glycols and related alcohols: In contrast to R Et4NBF4
R
aliphatic monoalcohols (1), 1,2-glycols and
(11) (12)
related compounds (2-methoxy alcohols,
R = H, R′ = Me; 82.5%
1,2-amino alcohols) can be easily oxidized R = R′ = Me; 72.2%
by the direct electrochemical method [12].
For example, 1,2-cyclopentanediol (9) af- (4)
fords diacetal (10) in 56% yield as the
main product (Eq. 3). 6.2.2
Indirect Oxidation of Alcohols
−1 OMe
OH −e, 2.13 F mol
OMe The direct electrochemical oxidation of
MeOH OMe
OH Et4NOTs alcohols is in many cases unselective
OMe
because of the high oxidation potentials
cis or trans-(9) (10) 56%
of the alcohols. One possible way to avoid
(3) this disadvantage is the use of a mediatory
Similarly, the electrooxidation of al- system (an indirect oxidation). Thereby
cohols carrying a β-methoxy or β- a mediator is converted to its oxidized
diethylamino group leads to the cor- form at a less positive potential than that
responding cleavage products in high required for the direct oxidation of the
yields [13]. alcohol, and the oxidized form of the
Me Me MeOH/ −2e Me Me
Et4NBF4 Me
Me
Anode: Carbon O
b a Cathode: Pt
OH 0°C
OMe
(7) (8) endo/exo = 97/3
Scheme 2 Conversion of alcohol into cyclic acetal by anodic oxygen insertion.

mediator oxidizes the alcohol (see also hydroxyl groups allowed the chemoselec-
Chapter 15). tive oxidation of 1,2-O-isopropylidene-α-D-
Mediators can be classified into two cate- xylofuranose (14) to the carboxylic acid (15)
gories: (1) mediators fixed to the electrode (Eq. 5) [16].
surface and (2) mediators that dissolve in
the solution. A representative of the first HO HO2C
O NiOOH/−e O
category is the nickel hydroxide electrode OH OH
Aq. K 2CO3
(NHE) and the second category involves O 8.0 F mol−1 O
inorganic (metal and halide ions) and or- O O
ganic mediators. (14) (15) 52%
(5)
6.2.2.1 Mediators Fixed to the Electrode α,β-Diols were oxidatively cleaved at the
Surface Cα –Cβ bond [16].
A variety of alcohols can be oxidized at the The conversion of primary alcohols to
nickel hydroxide electrode. The mediator aldehydes was achieved by using a biphasic
is presumably a nickel oxide hydroxide, system consisting of water and a nonpolar
which is fixed to the electrode surface organic solvent such as petroleum ether.
and is continuously reformed at the elec- Under these conditions, benzylic and
trode surface. allylic alcohols were oxidized with high
Primary and secondary alcohols (1) were selectivity to the aldehydes (for example,
converted to carboxylic acids (13) and ke- (16) to (17) in Scheme 4), while aliphatic
tones (2), respectively, in excellent yields alcohols were converted to aldehydes with
when the electrolysis was carried out using poor selectivity [17].
the nickel hydroxide electrode in aqueous Other examples of conversion using a
solution (Scheme 3) [15]. nickel oxide electrode are the oxidation
Primary hydroxyl groups are more easily of benzyl alcohols. A nickel foam elec-
oxidized than secondary ones. The differ- trode was used for oxidation [18] in this
ent reactivity of secondary and primary case and the mechanism was studied by
R1 Ni(OH)2, −e R1
OH R1CO2H or O
In aqueous NaOH
R2 or t-BuOH-H2O-KOH R2
(1) (13) 91% (2) 73%

R1 = C5H11, R2 = H R1 = C4H9, R2 = Me
Scheme 3 Oxidation of aliphatic alcohol at the nickel oxide electrode.
−e, 2.5 F mol−1

+
PhCH CHCH2OH PhCH CHCHO PhCH CHCO2H

Ni-anode
aq. K 2CO3
petroleum ether
(16) (17) (18)
54% 4%
Scheme 4 Oxidation of allyl alcohol at the nickel oxide electrode.

means of cyclic voltammetry and polariza- – H2 CrO4 : Propargylic acid was prepared
tion curves [19]. from propargylic alcohol by oxidation with
chromic acid (H2 CrO4 ) in H2 SO4 , and
the resultant Cr2 (SO4 )3 was electrochemi-
6.2.2.2 Mediators Dissolved in the cally regenerated to H2 CrO4 [31, 32]. This
Electrolyte mediator reaction is an example of the ex-
cell method, that is, a system consisting
6.2.2.2.1 Metal Ion Mediators A variety of an electrochemical cell and a chemi-
of metal salts and complexes have often cal reactor.
been used as soluble mediators for the – K6 SiW11 O39 Mn(I I ): Manganese ion-
indirect electrochemical oxidation of alco- substituted silicon polyoxotungstate can
hols. In particular, there have been many be used as a mediator for alcohol oxi-
studies on the oxidation of benzyl alcohols dation. Constant potential electrolysis of
to benzaldehydes. 1-phenylethanol at 1.25 V in the presence
– Ru complexes: Redox couples of Ru(II)/ of 5 mol% of the catalyst gave acetophe-
Ru(IV) [20–22], Ru(IV)/Ru(V) [23], and none in 61% yield [33].
Ru(IV)/Ru(VII) [24] were used for the – Bu2 Sn=O: Selective oxidation of 1,2-
oxidation of alcohols (1) to carbonyl com- diols to α-hydroxy ketones was electro-
pounds (2) or carboxylic acids (13). A chemically achieved in a double mediatory
double mediatory system consisting of system consisting of dialkyl tin oxide and
Ru(IV)/Ru(VIII) and Cl− /Cl+ redox cou- the bromide ion (Fig. 3) [34].
ples has been developed for the oxidation
The most interesting point in this
of alcohols and aldehydes [25–28].
oxidation was the high chemoselectivity.
– Co2 (SO4 )3 : Electrochemical oxidation For example, 1,2-diol (14) was selectively
of CoSO4 generated Co2 (SO4 )3 that reoxidized to give α-hydroxy ketone (15) in
acted with 1-naphthylmethanol in tri-butyl 84% yield at a current consumption of
phosphate to give 1-naphthaldehyde in 2 F mol−1 , even though the electrolysis
66% yield [29, 30]. was carried out in the presence of
R OH
Br−
R′ OH
R2Sn = O
2e R O
Br+
Fig. 3 Mediated oxidation
Anode R′ OH
of diols.
OH OH O OH
2 F mol−1
+
Bu2Sn = O
OH Et4N Br OH
in MeOH
(14) 5 equiv. at 0°C
(15) >99%
84% recovery
Scheme 5 Selective anodic oxidation of diol to α-hydroxyketone.

cyclohexanol (5 equiv. to 14) and in MeOH aldoximes (R−CH=N−OH) to nitriles

as a solvent (Scheme 5). (R−CN). The intermediates were nitrile
oxides (R−CN−O), which were reduced
at the cathode to nitriles. The yields
6.2.2.2.2 Halide Ion Mediators decreased in the order of Cl− > Br− >
–I −: Secondary alcohols are oxidized to I− > ClO4 − [38].
ketones and primary alcohols are oxidized – Cl − /ClO − : In the presence of polymer-
to esters, when iodonium ion is used as a supported phase transfer catalyst and
catalytic mediator as shown in Fig. 4 [35]. redox mediator Cl− /ClO− , the oxidation of
This method may have high potentiality benzyl alcohol to benzaldehyde or benzoic
in organic synthesis, since it requires only acid was achieved [39–41].
a catalytic amount of KI, whereas most
of the hitherto known oxidations usually – N O3 − : Nitrate ion worked as a me-
require more than one equivalent of the diator to oxidize simple alkanols to the
oxidizing agent. corresponding ketones [42].
– IO3 − /IO4 − : The periodate/iodate redox

mediatory system was applied to the con- 6.2.2.2.3 Organic Mediators Organic
version of 2,3-butandiol to acetaldehyde in mediators are very useful in electroorganic
80% current efficiency [36]. chemistry since their structural modifica-
tion may increase the selectivity of the
– Br − : α-Hydroxy-arylacetic acid esters oxidation. The first organic mediator exp-
were oxidized with bromide ion as a loited for oxidation in synthesis was thio-
mediator to give α-oxo-arylacetic acid anisole. Since then, there appeared a vari-
esters [37]. ety of other organic mediators such as tris-
– Cl − : Cl− is in general not as good arylamines, tetramethylpiperidinyl-1-oxy
as Br− and I− as a mediator, but (TEMPO), and N -hydroxyphthalimides
it worked well for the conversion of (NHPIs).
R1
I− O (RCO2CH2R)
R2
R1
2e I+ OH (RCH2OH)
R2 Fig. 4 Iodide-mediated
Anode oxidation of alcohols.
R1
PhSMe O
R2
R1
2e [PhSMe]++ OH
R2 Fig. 5 Thioanisole-mediated
Anode oxidation of alcohols.
– Thioanisole: A system utilizing thio- The compounds so far exploited cover a

anisole as an organic mediator was potential range from 0.8 to about 2.0 V
developed for the oxidation of secondary versus NHE [46].
alcohols to ketones (Fig. 5; 2-octanol to Oxidation reactions using mediators are
2-octanone; 99%, menthol to menthone; possible under very mild conditions with
92%, cyclododecanol to cyclododecanone; high selectivity. In fact, the oxidative
75%) [43]. The use of 2,2,2-trifluoroethanol cleavage of the carbon–sulfur bond of thio
as a solvent in the mediatory system ether (16) was easily possible by using
improved the yields [44]. mediator (17) (Scheme 6) [46].
Furthermore, a double mediatory sys- Furthermore, the mediator has been
tem consisting of alkyl methyl sulfide used for the bond cleavage of benzyl
and bromide ion was developed, which ethers, the oxidation of benzyl alcohol
made the oxidation of alcohols feasible at a to benzaldehyde, the oxidation of toluene
lower potential (1.1 V vs SCE) than that of derivatives to benzoic acid esters, and the
thioanisole (1.60 V vs SCE) [45]. Both the oxidation of aliphatic ethers [47].
alkyl methyl sulfide and the bromide ion – TEMPO: 2,2,6,6-Tetramethylpiperidinyl-
act together as mediators. Under this con- 1-oxy (20: TEMPO) works as a mediator for
dition 2-octanol was oxidized to 2-octanone the oxidation of primary alcohols to alde-
in 85% yield. hydes. The oxidation of secondary alcohols
Other organic mediators are as follows: is much slower than that of primary al-
– Trisarylamines: Trisarylamines have cohols as exemplified by the oxidation of
been successfully used as redox catalysts in (19) to (21) (Scheme 7) [48]. Active species
many indirect electrochemical oxidations. is the oxo-ammonium generated from
Their advantage is the possibility to adjust TEMPO.
their oxidation potential by selection of TEMPO has been structurally modified
the substituents on the aromatic rings. to bring about new selectivities [49, 50].
Anode
Ar3N+• Ar3N
R1 R1 +• R1 + Nu− R1
3
(17)
SR MeCN SR3 Nu
R2 H2O R2 R2 R2
(16) NaHCO3 (18)
[R3S•] 1/2 R3SSR3
Scheme 6 Indirect anodic cleavage of thioethers with trisarylamines.
OH OH
OH MeCN/LiCLO4, −2e O
2, 6-lutidine
H
(19) N (21)
75%
O• (20)
Scheme 7 Selective anodic oxidation of diols with TEMPO as mediator.

H
Me OH −e at +0.60 V vs Ag/AgCl Me O Me OH
+
(−)-sparteine
Ph Ph Ph
TEMPO-modified electrode
(22) MeCN, NaClO4 (23) (R)-(22)
Scheme 8 Enantioselective oxidation of alcohols with TEMPO/sparteine.
As a result, a highly enantioselective ox- electrochemical oxidation of benzyl alcohol

idation of (22) was achieved by using to benzaldehyde [61].
a TEMPO-modified graphite felt elec-
trode in the presence of (−)-sparteine,
6.3
where the enantiopurity of the remaining Oxidation of Phenols
(22) was >99% and the current effi-
ciency for (23) was >90% (Scheme 8) [51]. Phenols (1.8 V vs Ag/Ag+ ) [62], in particu-
However, this selectivity has been ques- lar phenolate ion (0.55 V vs Ag/Ag+ ) [63],
tioned [52]. are easily oxidized by the electrochemi-
A double mediatory system consisting cal method to give cationic intermediates,
of modified TEMPO and halide ion or which react with nucleophilic solvents
metal ion was also exploited for the such as MeOH, MeCN, or H2 O or with
oxidation of alcohols [53–55]. A number of the phenol itself, yielding dimers.
carbohydrates have been chemoselectively
oxidized at the primary hydroxyl group to 6.3.1
uronic acids [56]. Oxidation of Phenols to Quinones
– N-Hydroxyphthalimide: N -Hydroxyphth- Sterically hindered phenol (24) was elec-
alimide (NHPI) was shown to be a trochemically oxidized to afford a phenox-
mediator for the electrochemical oxidation enium ion (25) that reacted with O- and
of (1) to (2) (Eq. 6) [57, 58], although the N -nucleophiles to yield a cyclohexadienyl-
yields of (2) were not always satisfactory. A protected amino acid (26) (Scheme 9) [64].
large deuterium isotope effect (kH /kD = Similarly, 2,6-di-t-butyl-phenol was oxi-
10.6) was observed in the oxidation dized to 2,6-di-t-butyl-p-quinone in 60%
of benzhydrol [59]. Recently, tetrafluoro- yield under conditions of MeOH–AcOH
NHPI was found to be efficient for the containing NaBF4 [65].
oxidation of borneol [60].
O
6.3.2
C, C−Bond Formation
N OH, −e
R1 R1 A variety of phenol couplings have been
(NHPI) O
OH O described. Those reported before 1991
R2 R2
have been reviewed [66]. 2-Naphthol (27)
(1) (2)
was oxidized to 1,1 -binaphthol (28) in
R = Ph, R′ = Me 87%
high current efficiency on a graphite felt
R = Me, R′ = H 93%
electrode coated with a thin poly(acrylic
(6) acid) layer immobilizing 4-amino-2,2,
– Flavin: Riboflavin-2 ,3 ,4 ,5 -tetraacetate 6,6-tetramethylpiperidinyl-1-oxy (4-amino-
works as a mediator in the photoinduced TEMPO) (Scheme 10) [67].
6.3 Oxidation of Phenols 181
+
OH O
−2e, −H+
1.2 V
CH2Cl2, Bu4NBF4 Me CO2H
, −H+
NHCO2Bn
(24) (25)
O
Me
O
NHCO2Bn
O
(26) (74%)
Scheme 9 O-protection of amino acids by oxidative coupling with phenols.
OH
−2e
MeCN, NaClO4 2
OH
TEMPO-modified
graphite felt anode
(27) (28) 98.6%
Scheme 10 Anodic coupling of β-naphthol mediated by TEMPO.
Phenols (29) substituted with bromo- the reaction of the resulting benzylic
and chloro-atoms in the o, o -positions cation with MeOH (Scheme 12) [69–71].
were oxidized to diaryl ethers (30), The efficiency of this C−C bond forming
while the iodo-substituted phenols (29) reaction depends on the olefinic sub-
provided the diaryls (31) as major products stituents R.
(Scheme 11) [68]. Phenoxy cations (35) electrochemically
The electrochemical oxidation of 4- generated from phenols (34) react with
(2 -alkenylphenyl)phenols (32) in MeCN/ olefins to afford two types of bicyclic
MeOH affords spirodienones (33) aris- compounds (36) and (37), depending on
ing from cyclization by the intramolec- the substituents (X, Y, Z), the solvent used
ular addition of the 4-position of the for electrolysis, and the structure of the
phenol to the olefinic side chain and olefin (Scheme 13) [72].
OH X OH OH OH
X O X X X X
−2e −2e
X = Cl or Br X=I
X R
R R R R
(30) (29) (31)
Scheme 11 Anodic C,C- and C,O-coupling of phenols.

R R OMe
−2e
HO O
MeCn/MeOH (4/1)
AcOH (30 eq.)
(32) Pt electrodes (33)
R = Me 97%
Scheme 12 Spirodienones by intramolecular phenol–alkene coupling.
X O
Y R
R
O
R′
(36) R′
Z = OMe
Y Y Y
Z Z Z R2
−e, −H+, −e R3
+ MeO Z O
MeOH R2
X X
X
OH O O R3 Y X
MeO
(34) (35) (37)
Scheme 13 Anodic cycloadditions with phenols and alkenes.
R2
OH O O
R2 R1
R1 R1
−2e
+
MeNO2
LiClO4
OH O O
(38) (39) (40) (41)
Scheme 14 Anodic cycloadditions with hydroquinone and dienes.
Similarly, an intramolecular C−C bond supported the Diels–Alder reaction be-

formation was observed in the electrolysis tween in situ generated quinone (39)
of other phenols with olefinic functionality and diene (40) to give the adduct
in the side chain [73–76]. (41) [77, 78].
The electrochemical oxidation of phe-
nols produces quinones that can be used as
dienophiles for the Diels–Alder reaction. 6.4
A typical example is shown in Scheme 14, Oxidation of Carbonyl Compounds
where a lithium perchlorate/nitromethane
system and an electrode coated with The electrochemical oxidation of carbonyl
a PTFE [poly-(tetrafluoroethylene)] fiber, compounds is achieved by direct and
to create a hydrophobic reaction layer, indirect methods.
6.4 Oxidation of Carbonyl Compounds 183
6.4.1 For example, 2-hexanone in MeCN

Direct Oxidation of Carbonyl Compounds gave 5-acetamino-2-hexanone (44) in 40%
yield (Scheme 17) [82], and 2-pentanone
α-Cleavage was observed as the main was oxidized in trifluoroacetic acid to
route in the electrochemical oxidation give a mixture of 4-trifluoroacetoxy-2-
of aliphatic α-branched ketones (42) pentanone (24%) and 3- and 4-penten-
(Scheme 15) [79, 80]. 2-one (6%) [83]. A mechanism involving
For example, acetyladamantane and intramolecular hydrogen abstraction by a
isopropyl methyl ketone gave 1-adamantyl- ketone cation radical that forms a car-
acetamide in 85% yield and N - benium ion via a [1,5]-hydrogen shift
acetyl-isopropylamine in 46% yield, was proposed.
respectively [79]. A similar α-cleavage An α-cleavage with subsequent [1,2]-
was observed in the electrochemical hydrogen shifts was observed in the elec-
oxidation of the α-branched cyclic ketone trochemical oxidation of cyclohexanone
(43) using Et3 N-5HF as an electrolyte (Eq. 7) [84].
(Scheme 16) [81].
On the other hand, acyclic ketones, O O O
when oxidized in trifluoroacetic acid [82]
−e O O
or in MeCN [83], gave dehydrogenated +
ketones and products substituted at
the remote (γ , δ, or ε) positions. (7)
R2
R2 R2 Y
R1 −2e + YH
O 1
R + + O + R1 + O
−2H
R3 R3
Y R3
(42)
Scheme 15 Anodic α-cleavage of acyclic ketones.
O O
−2e F MeOH MeO2C F
F
2.0 V vs Ag/Ag + MeONa
Et3N-5HF, MeCN
(43) 3.1 F mol−1 81%
Scheme 16 Anodic α-cleavage of cyclic ketones.
Me −2e, 2.2 F mol−1 Me NHCOMe

O O
LiClO4, MeCN
Me 2.3 V vs Ag/Ag + Me
(44) 40%
Scheme 17 γ -Acetamidation of ketones via a ketone radical cation and a [1,5]-hydrogen shift.
6.4.2 A similar electrochemical oxidation of

Indirect Oxidation of Carbonyl Compounds aromatic aldehydes to their corresponding
methyl esters was achieved by using flavo-
Indirect oxidation of carbonyl compounds thiazolio-cyclophane as a mediator [87].
using mediators leads to better results than Ketones and aldehydes (51) are oxidized
the direct oxidation. to α-hydroxy ketals and acetals (52) by
– P bO2 anode: Camphor was electro- electrolysis in MeOH containing halide
chemically oxidized at Pb/PbO2 as an ion under basic conditions (Eq. 9) [88].
anode material in 1 M H2 SO4 /MeCN to
O MeO OMe
give 1,2-campholide (45) as the main prod- −2e
R1 R1
uct (88%) and 6% (46) (Scheme 18) [85]. R3 KI, KOH R3
R2 MeOH R2 OH
– Ni electrode: The nickel hydroxide elec-
trode was nicely used for the oxidation (51) (52) R3 = alkyl or H
of aldehyde (47) to carboxylic acid (48) (9)

(Scheme 19) [15]. A reaction mechanism as described in
– Halide ion: Aldehydes (49) were trans- Scheme 20 was proposed.
formed to methyl esters (50) by way of Under similar reaction conditions, some
electrolysis in MeOH containing an al- ketones such as (53) gave products via
kali metal halide as shown in Eq. (8) [86]. an electrochemically induced Favorskii
KI and KBr gave satisfactory results. In rearrangement (Eq. 10) [89, 90].
a two-phase system consisting of water
O CO2Me CO2Me
and n-BuOH, aldehydes were converted to
n-Bu esters. −e
MeOH, NaI +
−2e 11.0 F mol−1
R CHO R CO2Me
MeOH (53) (54) (55)
KI or KBr 82% 13%
(49) (50)
R = cyclohexyl; KI, 100% (10)
KBr, 99% Electrochemical oxidation of higher alde-
(8) hydes (56) in the presence of secondary
−e 8 F mol−1
O O + O
Pb/PbO2 anode
stainless steel cathode O O
1 M H2SO4
MeCN/H2O (1/1)
(45) (46)
88% 6%
Scheme 18 Anodic Bayer-Villiger oxidation.
Ni(OH)2, −e
CHO CO2H
Me t-BuOH-H2O-K2CO3 Me
(47) (48)
68%
Scheme 19 Anodic oxidation of aldehydes to carboxylic acids at the nickel oxide electrode.
6.5 Oxidation of Carboxylic Acids 185
OH OH
R1 I−, −2e R1 OMe Base
(51)
R3 R3 −HI
R2 R2 I
OMe
O MeOH
R1 (52)
R3
2
R
Scheme 20 Anodic conversion of ketones to α-hydroxy ketals.
amines in a mixed solvent of water and still a widely applied method because
t-BuOH containing KI gave α-amino ke- of its specificity and versatility, which
tones (57) (Scheme 21) [91]. The reaction cannot be achieved by other chemical
involves enamines as intermediates. methods. The reaction is initiated by a
Electrochemical oxidation of easily ac- one-electron transfer from a carboxylate
cessible alkyl aryl ketones (58) in trimethyl ion (60) to the anode, yielding a radical
orthoformate containing a small amount (61) that dimerizes to a homocoupling
of iodine or organo-iodo compounds gave product (62) (path a, Scheme 23, termed
methyl α-alkylalkanoates (59) in high Kolbe reaction) [94–96]. The reaction is
yields (Scheme 22) [92]. The products (59) very useful for the preparation of higher
are precursors for drugs possessing anti- alkanes or 1,n-diesters. In addition to
inflammatory and analgesic activities. the Kolbe reaction, it has been found
in the beginning of 20th century that
depending on the reaction conditions
6.5 and the structure of carboxylic acid, a
Oxidation of Carboxylic Acids carbenium ion (63) can be formed in a two-
6.5.1 electron oxidation (path b, Scheme 23),
The Kolbe Reaction which is termed non-Kolbe reaction or
Hofer–Moest reaction [94–97].
The Kolbe reaction is the oldest Both types of reaction are applied in
electroorganic reaction, discovered in the organic synthesis. Some representative
middle of the 19th century [93], but is examples are given below.
O
−2e
R CH2CHO + N
KI R
N H2O-t-BuOH
(56) H (57) R = n-Pen; 41%
Scheme 21 Anodic conversion of ketones to α-aminoketones.
R
−2e
X X
CH(OMe)3
R I2 or RI CO2Me
(58) LiClO4 •3 H2O (59)
X = H, R = Me; 100%
X = i-Bu, R = Me; 80%
Scheme 22 Anodic conversion of aryl alkyl ketones to methyl phenyl acetates.

1/2 R R Kolbe reaction

Path a
(62)
−e
R CO2− −CO2
[R•]
(60) (61) −e
NuH
Path b [R+] R Nu Non-Kolbe reaction
−H+
(63) (64)
NuH; nucleophile
Scheme 23 Anodic decarboxylation of carboxylic acids.
R′ CO2− R R′
−e
(60)′ 62′ R R
−CO2
R′• (61)′
(ii)
(66)
−e (i) (61) (65)
R CO2 − R•
−CO2
R R
(iii) R
(60) (61) (62)
(iii-a) (61)
(iii-b)
R
R (iii-c) (61)′ R 67
• (iii-d)
H• R′
65 (68)
R
(iii-e)
(69)
R R
61′
•
R′
(70)
(71)
Scheme 24 Reaction of radicals generated by anodic decarboxylation of carboxylic acids.
The Kolbe coupling reaction and its radical (65) formed by the addition of (61)
modifications are schematically summa- to olefins.
rized in Scheme 24. The Kolbe coupling The reaction of type i is utilized for
reaction produces dimer (62) through a the preparation of a variety of dicarboxylic
radical (61) generated from carboxylate acids. Scheme 25 shows the synthesis of
ion (60) (type i). Modified Kolbe reactions a C-disaccharide (73) from a carbohydrate
are the cross-coupling reactions between carboxylic acid (72) [98].
[R•] (61) and [R •] (61 ) generated from In order to obtain the coupling product
a co-acid (60 ) (type ii), and the reac- (62) in good yield, factors such as anode
tion through trapping of (61) with olefins material, solvent, pH, and structure of the
(type iii). The reaction of type iii can be substrate are critical. In general, the follow-
further subdivided into five types iii-a–e ing conditions are recommended for the
according to the subsequent reaction of Kolbe reaction; solvent: MeOH containing
OAc OAc
−e, −CO2
AcOCH2 CH2CO2H AcOCH2 CH2 2
52%
AcO OAc AcO OAc
(72) (73)
Scheme 25 C-disaccharides by anodic decarboxylation of carbohydrate carboxylic acids.
a small amount of water (0.25–2.5%), an excess amount of a co-acid (76) was

or pure MeOH, in a few cases, N, N - used (Scheme 27) [99, 100].
dimethylformamide (DMF) or MeCN have The addition reaction of type iii can be
also been used; current density: 0.1 to further subdivided into type iii-a–e.
1.0 A cm−2 ; supporting electrolyte: alkali – Type iii-a: The formation of (66) is
metal hydroxide (2–5%), in some cases, tri- found in the electrolysis of partially
alkylamines or pyridine have been applied; neutralized trifluoroacetic acid in the
anode materials: platinum, platinized tita- presence of diallylamine (78). It provides
nium, or glassy carbon. The use of soft the crystalline hydrochloride of cis-3,4-bis-
carbon anode results in the formation of (2,2,2-trifluoroethyl)pyrrolidine (79) in 8%
carbenium ion (63). yield (Scheme 28) [101].
The coupling reactions are in general Another example of type iii-a is the
limited to primary carboxylic acids trifluoromethylation of double bonds by
(RCH2 CO2 H). α-Branched carboxylic electrolysis of trifluoroacetic acid in
acids lead to non-Kolbe products. the presence of olefins. Methyl vinyl
However, carboxylic acid (74) with the ketone, vinyl acetate, diethyl fumarate,
electron-attracting trifluoromethyl group diethyl maleate, N -ethylmaleimide, and
in the α-position yields the Kolbe coupling 2,5-dihydrothiophene-1,1-dioxide were ex-
product (75) (Scheme 26) [99, 100]. amined as olefins. The products were bis-
A reaction of type ii (heterocoupling) trifluoromethylated additive dimers (66)
occurred for (74) in satisfactory yield when (type iii-a) and monomers (67) (type
CF3
CF3 −e, 10 F mol−1 OH
HO
Pt electrodes 0°C
HO CO2H MeOH-MeONa CF3
(10 mol %)
(74) (75)
95% dl/meso = 1/1
Scheme 26 Anodic homocoupling by Kolbe electrolysis.
Cl −e, 6 F mol−1 Cl
(74) + HO
Pt electrodes
CO2H MeOH-MeONa CF3
(10 mol %)
(76) (77)
1:10 70%
Scheme 27 Anodic heterocoupling by Kolbe electrolysis.

CF3 CF3
−2e
CF3CO2− + NH
CF3CO2H
acetone-H2O N
NaOH H
(78) (79)
8%
Scheme 28 Anodic additive coupling by Kolbe electrolysis.
iii-b) [102–104]. Electrooxidation of trifluo- Similarly, dialkylated succinimide (82) was

roacetic acid in the presence of acrylonitrile obtained in the electrolysis of acid (80) with
in an MeCN-water solution gave 2,3- maleimide (81) (Scheme 29) [107].
bis(2,2,2-trifluoroethyl)succinonitrile in 20
Electrochemical trifluoromethylation of
to 25% yield with a 1 : 1 ratio of the 3-sulfolene in a CF3 CO2 H/CF3 CO2 Na/
diastereoisomers [105]. CH3 CN/H2 O system gave a complex
– Type iii-b: This reaction leads to products mixture consisting of meso- and dl-3,4-
(67). The electrochemical oxidation of the bis(trifluoromethyl)sulfolanes as the ma-
sodium salts of acetic, propionic, and jor components [108].
isovaleric acids in the presence of ethylenic Type iii-c reaction leads to the forma-
compounds bearing electron-withdrawing tion of (68). In the case of 6-alkenoic
substituents gives 1,2-dialkylated adducts acids an intramolecular addition takes
as the main products. A methyl radical place. The Kolbe electrolysis of β-(N -
generated from an acetate ion reacts allylamino)alkanoate (83) in the presence
with diethyl fumarate to give diethyl of a co-acid (84) gave 3-alkyl-substituted
2,3-dimethylsuccinate in 80% yield [106]. pyrrolidine (85) through an intramolecular
O O
−2e
+ N Et NaOH N Et
CO2H MeCN-H2O
O O
(80) (81) (82)

66%
Scheme 29 Addition of radicals generated by Kolbe electrolysis.
CO2H
C5H11
−e
+ C5H11CO2H
NaOH
N (4 eq.) N
Pt electrodes
undivided cell
COMe COMe
(83) (84) (85)
46%
Scheme 30 Additive cyclization by way of Kolbe electrolysis.

CF3
NC −2e CN
CF3CO2− + CN NC
CF3CO2H
MeCN-H2O
(86) NaOH at 50°C (87)
65%
Scheme 31 Addition of radicals generated by Kolbe electrolysis.
addition of the initially generated radical, allows the introduction of different sub-
followed by a heterocoupling with a pentyl stituents R by varying the co-acid RCO2 H.
radical (Scheme 30) [109].
A type iii-d reaction leads to the for- 6.5.2
mation of (69). Trifluoromethyl radicals The Non-Kolbe Reaction
generated electrochemically from triflu-
oroacetate can attack electron-deficient 6.5.2.1 Reaction with Nucleophiles
olefins leading to trifluoromethylated car- Depending on the anode material used, the
bon radicals whose chemical and electrooxidation of a carboxylic acid can lead to a
chemical follow-up reactions can be con- carbenium ion [R+ ], which is trapped by a
trolled by current density, reaction temper- nucleophile (NuH) to afford a one-carbon-
ature, and substituents of the olefins. With shortened product (Scheme 33) [112].
fumaronitrile (86) at 50 ◦ C the monotri-
fluoromethylated compound (87) was ob-
6.5.2.2 Rearrangement
tained in 65% yield (Scheme 31) [110].
The intermediate cation [R+ ] (63) often
With type iii-e reactions compounds (71)
rearranges to a more stable cation [R+ ]
are formed. A radical tandem reaction ini-
(63 ) that is trapped by NuH (Eq. 11).
tiated by the Kolbe electrolysis of (88) gave
tricyclic compounds (89) in a one pot reac- NuH
[R+] [R′+] R′ Nu
tion (Scheme 32) [111]. The electrochem- Rearrangement −H+
ical decarboxylation avoids the usually (63) (63)′
applied toxic tin hydride as reagent and (11)
O O
−2e
( )n RCO2H
( )n
−2CO2
CO2H −2H+
( )m ( )m •
(88) O O
•
( )n ( )n R
R•
( )m ( )m
(89)
n = 1∼3, m = 1∼3; 33–42%
Scheme 32 Radical tandem cyclization initiated by Kolbe electrolysis.

R R R
−2e NuH
CO2H +
+ Nu
−CO2, −H
R′ R′ R′
NuH, AcOH, MeOH
Scheme 33 Anodic substitution by way of the Non-Kolbe reaction.
OH O
−2e H2
CO2− dl-muscone
Pyridine-H2O
(9/1)
Me K+ Me
(90) (91)
30%
Scheme 34 1,2-Rearrangement induced by the Non-Kolbe reaction as key step for a
muscone synthesis.
Electrolysis of β-hydroxy carboxylic acid

(90) gave ketone (91) as the main prod- −2e
uct, which was converted to dl-muscone CO2H
Water-pyridine
Et3N
(Scheme 34) [113]. The migratory aptitude CO2H
of alkyl substituents at the ß-position in (92) cis-endo (93)
the intermediate ß-hydroxy carbenium ion 40%
was scrutinized to show that vinyl, cy-
(12)
clopropyl, and benzyl groups rearrange
On the other hand, 1,1-dicarboxylic
predominantly.
acids gave ketones as 1,1-elimination
Several similar rearrangements start-
products [119].
ing from γ -hydroxy [114] and β-alkoxy
acids [115] were reported.
6.5.2.4 Oxidative Decarboxylation of
6.5.2.3 Olefin Formation α-heteroatom-substituted Carboxylic Acids
Electrochemical oxidation of 1,2-dicarbo-
xylic acids provides an easy route to Oxidative decarboxylation of α-oxy-carbo-
olefins [116–118]. For example, 1,2- xylic acids: 2,3,4-tri-O-methyl-ß-D-gluco-
dicarboxylic acid (92) was decarboxy- pyranosiduronic acid (94) was electrolyzed
lated by electrochemical oxidation to give under several reaction conditions to give a
olefin (93) as the 1,2-elimination product mixture of stereoisomers (95) as shown in
(Eq. 12) [116, 117]. Scheme 35 [120].
CO2H OMe
OOMe OOMe
OMe −e OMe
Na salt
OMe in MeOH OMe
OMe OMe
(94) (95) a:b = 63:33
Scheme 35 Anodic decarboxylation of a hexose to a pentose.

R′′ R′′ R′′

R′
−2e
R′ + MeOH
R′
N COOH N N OMe
−CO2
COR COR COR

(96) (97) (98)
Scheme 36 Anodic decarboxylation of N-acyl α-amino acids to a N-acycl iminium intermediates.
BnO2C O BnO2C O
i-Bu i-Bu
N C −2e, 2.3 F mol−1 N C
N COOH N OMe
H MeOH H
Et3N
(99) (100)
93%
Scheme 37 Anodic decarboxylation of a dipeptide.
Oxidative decarboxylation of α-amino (103) gave a N, O-acetal (104) with a 1 : 1

carboxylic acid: The electrochemical mixture of diastereoisomers in 75% yield
oxidation of N -acyl-α-amino acids (96) (Eq. 14) [124]. In general, the diastereose-
in MeOH affords N, O-acetals (98) lectivity (ds) observed in the electrochem-
through acyliminium intermediates (97) ical oxidation is lower than that in the
(Scheme 36) [121]. Lewis acid–catalyzed replacement of the
methoxy group with nucleophiles. This is
This reaction has been applied to the exemplified by the introduction of an allyl
synthesis of a variety of pharmaceutically group into (104) with a diastereoselectivity
interesting compounds. of 4/1.
α-Amino acid (99) possessing two
stereogenic centers was electrolyzed in OSit-BuMe2
−2e
OSit-BuMe2
MeOH to produce N -acyl-N, O-acetal CO2H OMe
MeOH
(100) (Scheme 37) [122].
NHCO2Me NHCO2Me
Correspondingly, 4-acetoxy-2-azetidin- (103) (104)
one (102) was prepared from 4-carboxy-2- 75%, 1/1 mixture
azetidinone (101) by a non-Kolbe reaction
(14)
(Eq. 13) [123].
For the cyclic compound (105) de-
CO2H OAc
rived from serine methyl ester, a high
−2e, 5.0 F mol−1 diastereoselectivity was observed (85%
NH MeCN-AcOH (3/1) NH yield, 90% ds) (Eq. 15) [124].
O 0.5 M AcONa O
(101) (102) O O
i-Pr −2e i-Pr
76%
N AcOH N
(13) CO2H OAc
The stereochemistry in the electrochem- MeO2C MeO2C
ical oxidation of (96) yielding N, O-acetals (105) (106)
(98) is of timely interest. The electrochemi- 85%, 90% ds
cal oxidation of acyclic threonine derivative (15)

OTBDMS OTBDMS
H H CO H
2
−e, 11 F mol−1 H H OAc
MeCN-AcOH (4/1)
NH AcONa (4.5 equiv.) NH
O O
(107) (108)
84%
Scheme 38 Diastereoselective anodic decarboxylative substitution of a β-lactam.
O O O
HN O HN O −2e HN O
or
MeOH/AcONa
HO2C Me HO2C Me MeO Me
trans-(109) cis-(103) (110)
trans/cis = 77/23
Scheme 39 Diastereoselective anodic decarboxylative substitution of a threonine derivative.
However, electrolysis of N -methoxy- Electrochemical oxidation of exo- or

carbonyl-O-[(t-butyl)dimethylsilyl]hydroxy- endo-carboxylic acid (111) gave only 2-
proline in MeOH also led to a substitu- exo-methoxynorbornene derivative (112) in
tion of the CO2 H group by the MeO group 95% yield (Scheme 40) [128].
with no diastereoselectivity [125]. Since the oxidation of (96) proceeds
On the other hand the electrolysis of through the acyliminium ions (97)
(107) afforded optically pure (108) in 84% (Scheme 36), where the positive charge
yield (Scheme 38) [123]. Thus the stereo- is stabilized by the adjacent nitrogen
chemistry differs strongly depending on atom, it should lead to racemic acetals
the kind of carboxylic acid used. (98) from enantioenriched acids (96). In
The electrochemical substitution of ei- fact, the electrolysis of N -benzoylated L-
ther stereoisomer of the N -acyl-α-amino proline (113) gave racemic N, O-acetal
carboxylic acid (109) led to product (110) (114) regardless of the anode material used
in 75% yield with a trans/cis ratio of 77/23 (Scheme 41) [129].
(Scheme 39) [126, 127], which is in con- On the other hand, in contrast with the
trast to the stereoselectivity (>97.5% ds) non-Kolbe reaction of (113), that of L-serine
observed in the substitution of the methoxy derivative (115) gave an optically active α-
group of (110) with dibenzoylmethane in methoxylated product (116) with 39% ee
trifluoroacetic acid. when graphite was used as the anode
−2e
or
CO2H CO2H MeOH OMe
NaOMe
NHAc CO2H NHAc
exo-(111) endo-(111) (112)
95%
Scheme 40 Anodic decarboxylation of a norbornene carboxylic acid.

−2e, 2 F mol−1
COOH OMe
N Pt cathode N
graphite or Pt anode
COPh NaOMe in MeOH COPh
−20°C, 75% yield
(113) (114)
(0% ee)
Scheme 41 Anodic decarboxylation of a N-phenacyl proline.
O O
Me −2e, 2 F mol−1 Me ∗
COOH OMe
Me N Pt cathode Me N
graphite anode
COPh NaOMe in MeOH COPh
−20°C
(115) (116)
(39% ee)
Scheme 42 Anodic decarboxylation of a substituted N-phenacyl oxazolidinecarboxylic acid with
partial retention of configuration.
material (Scheme 42) [129]. The absolute 6.5.3

configuration of the enriched enantiomer Oxidation of Amides
of (116) was made probable to be S. This
is the first example of memory of chirality Electrolysis of amides in MeOH contain-
in carbenium ion chemistry. ing the bromide ion efficiently led to
The electrolysis of α-phenylthiocarboxy- products of the Hofmann rearrangement
lic acids (117) in MeOH containing LiClO4 (for example, 119 to 120; Scheme 43) [131].
gave the corresponding aldehyde acetals This reaction, named the electrochemically
(118) (Eq. 16) [130]. induced (E-I) Hofmann rearrangement,
is achieved without any bromine and
base under mild and neutral reac-
CO2H −2e OMe
R R tion conditions.
SPh MeOH OMe (16) Thus, for example, an epoxy functional
LiClO4
(117) (118) group in the alcohol part remained intact
−2e
CONH2 KBr NHCO2Me
MeOH
(119) (120)
7.5 F mol−1, 71%
Scheme 43 Electrochemically induced Hofmann rearrangement.
−2e
O
O
Me O
Me
CONH2 N O
HO H
(121)
MeCN, Et4NBr (122)
53%
Scheme 44 Electrochemically induced Hofmann rearrangement with insertion of an epoxy alcohol.

−2e, 2.2 F mol−1

NHBoc NHBoc NHBoc
Et4NBr +
CO2Me CF3CH2OH/MeCN NH CO2Me
O NH2 Pt electrodes O N O
H
at 60°C CO2CH2CF3
(123) (124) (125)
80% (>99.9% ee) 0%
Scheme 45 Electrochemically induced Hofmann rearrangement of N-Boc glutamine with retention
of configuration.
during the conversion of (121) to (122) 5. H. Lund, M. M. Baizer, (Eds.), Organic Elec-
(Scheme 44) [132, 133]. trochemistry, 3rd ed., Marcel Dekker, New
However, the conditions of the E-I Hof- York, 1991.
6. O. Hammerich, B. Svensmark in Organic
mann rearrangement are not yet suitable Electrochemistry (Eds.: H. Lund, M. M.
for substrates that are unstable under Baizer), 3rd ed., Marcel Dekker, New York,
weakly basic conditions, since the elec- 1991, pp. 615–657.
trochemically generated bases (EGB) may 7. G. Sundholm, J. Electroanal. Chem. 1971,
be present in the vicinity of the cathode. 31, 265–267.
For example, the E-I Hofmann rearrange- 8. K. Shirai, O. Onomura, T. Maki et al., Tetra-
hedron Lett. 2000, 41, 5873–5876.
ment of (2S)-N 2 -Boc-protected glutamine
9. P. C. Scholl, S. E. Lentsch, M. R. Van de
methyl ester (123) in MeOH containing Mark, Tetrahedron 1976, 32, 303–307.
the bromide ion yielded the desired Hof- 10. I. E. Markó in Novel Trends in Electroorganic
mann rearrangement product in only a Synthesis (Ed.: S. Torii), Springer-Verlag,
low yield (28%) and a by-product (125) Tokyo, 1998, pp. 7–10.
that might be generated by a base- 11. Y. Matsumura, T. Asano, T. Shono, Denki
Kagaku 1994, 62, 1154–1157.
catalyzed cyclization of (123). On the
12. T. Shono, Y. Matsumura, T. Hashimoto
other hand, the transformation of (123) et al., J. Am. Chem. Soc. 1975, 97,
to (124) was successfully achieved with- 2546–2548.
out any formation of (125) and no loss 13. T. Shono, H. Hamaguchi, Y. Matsumura
of the optical purity by electrolysis using et al., Tetrahedron Lett. 1977, 3625–3628.
the CF3 CH2 OH/MeCN solvent system in 14. E. A. Mayeda, J. Am. Chem. Soc. 1975, 97,
which CF3 CH2 OH might play an impor- 4012–4015.
15. H. J. Schäfer in Topics in Current Chemistry
tant role to control the basicity caused by (Ed.: E. Steckhan), Springer-Verlag, Berlin,
the EGB (Scheme 45) [134]. Germany, 1987, pp. 101–129, Vol. 142.
16. H. J. Schäfer, R. Schneider, Tetrahedron
References 1991, 47, 715–724.
17. R. Schneider, H. J. Schäfer, Synthesis 1989,
1. N. L. Weinberg, (Ed.), Technique of Electroor- 742–743.
ganic Synthesis, John Wiley & Sons, New 18. P. Cognet, J. Berlan, G. Lacoste et al., J.
York, 1974. Appl. Electrochem. 1996, 26, 631–637.
2. A. J. Fry, Synthetic Organic Electrochemistry, 19. B. J. Hwang, B.-Y. Yu, Y. L. Lo, J. Chin. Inst.
2nd ed., Wiley, New York, 1989. Chem. Engrs. 1997, 28, 455–462.
3. E. Steckhan, (Ed.), Topics in Current Chem- 20. B. A. Moyer, M. S. Thompson, T. J. Meyer,
istry, Springer-Verlag, Berlin, Germany, J. Am. Chem. Soc. 1980, 102, 2310–2312.
1987, Vol. 142. 21. W. Kutner, T. J. Meyer, R. W. Murray, J.
4. T. Shono, Electroorganic Synthesis, Acade- Electroanal. Chem. Interfacial Electrochem.
mic Press, London, 1991. 1985, 195, 375–394.
22. V. J. Catalano, R. A. Heck, C. E. Immoos 46. E. Steckhan, Topics in Current Chemistry,

et al., Inorg. Chem. 1998, 37, 2150–2157. Springer-Verlag, Berlin, Germany, 1987,
23. C. M. Che, K. Y. Wong, T. C. W. Mak, J. pp. 1–69, Vol. 142.
Chem. Soc., Chem. Commun. 1985, 988–990. 47. K.-H. G. Brinkhaus, E. Steckhan,
24. S. Torii, A. Yoshida, H. Tanaka in Novel W. Schmidt, Acta Chem. Scand., Ser. B 1983,
Trends in Electroorganic Synthesis (Ed.: 37, 499–507.
S. Torii), Kodansha, Tokyo, 1995, pp. 141, 48. M. F. Semmelhack, C. S. Chou, D. A.
142. Cortes, J. Am. Chem. Soc. 1983, 105,
25. S. Torii, T. Inokuchi, T. Sugiura, J. Org. 4492–4494.
Chem. 1986, 51, 155–161. 49. T. Osa, Y. Kashiwagi, K. Mukai et al., Chem.
26. S. Torii, T. Inokuchi, S. Matsumoto et al., Lett. 1990, 75–78.
Bull. Chem. Soc. Jpn. 1989, 62, 2108–2110. 50. F. Kurashima, Y. Kashiwagi, C. Kikuchi
27. S. Torii, T. Inokuchi, S. Matsumoto et al., et al., Heterocycles 1999, 50, 79–81.
Bull. Chem. Soc. Jpn. 1990, 63, 852–855. 51. Y. Kashiwagi, Y. Yanagisawa, F. Kurashima
28. M.-L. Tsai, T.-C. Chou, Denki Kagaku 1994, et al., Chem. Commun. 1996, 2745, 2746.
62, 1169–1172. 52. E. M. Belgsir, H. J. Schäfer, Chem.Commun.
29. R. E. Ballard, A. McKillop, Bri. UK Pat. 1999, 435, 436.
Appl. GB 2125068. 53. T. Inokuchi, S. Matsumoto, T. Nishiyama
30. R. E. Ballard, A. McKillop, Chem. Abstr. et al., J. Org. Chem. 1990, 55, 462–466.
1984, 101, 30 215v. 54. T. Inokuchi, S. Matsumoto, S. Torii, J. Org.
31. W. Zhou, X. Jin, G. Huang et al., Huaxue Chem. 1991, 56, 2416–2421.
Shijie 1982, 23, 164, 165. 55. T. Inokuchi, K. Nakagawa, S. Torii, Tetrahe-
dron Lett. 1995, 36, 3223–3226.
32. W. Zhou, X. Jin, G. Huang et al., Chem.
56. K. Schnatbaum, H. J. Schäfer, Synthesis
Abstr. 1984, 100, 128 708n.
1999, 864–872.
33. M. Sadakane, E. Steckhan in Novel Trends
57. M. Masui, T. Ueshima, S. Ozaki, J. Chem.
in Electroorganic Synthesis (Ed.: S. Torii),
Soc., Chem. Commun. 1983, 479–480.
Springer-Verlag, Tokyo, 1998, pp. 139–142.
58. M. Masui, T. Kawaguchi, S. Ozaki, J. Chem.
34. T. Maki, K. Fukae, H. Harasawa et al.,
Soc., Chem. Commun. 1985, 1484, 1485.
Tetrahedron Lett. 1998, 39, 651–654.
59. C. Ueda, M. Noyama, H. Ohmori et al.,
35. T. Shono, Y. Matsumura, J. Hayashi et al.,
Chem. Pharm. Bull. 1987, 35, 1372–1377.
Tetrahedron Lett. 1979, 165–168. 60. K. Gorgy, J.-C. Lepretre, E. Saint-Aman
36. A. Yoshiyama, T. Nonaka, M. M. Baizer et al., Electrochim. Acta 1998, 44, 385–393.
et al., Bull. Chem. Soc. Jpn. 1985, 58, 61. M. Ishikawa, H. Okimoto, M. Morita et al.,
201–206. Chem. Lett. 1996, 953, 954.
37. H. Maekawa, Y. Ishino, I. Nishguchi, Chem. 62. E. R. Altwicker, Chem. Rev. 1967, 67,
Lett. 1994, 1017–1020. 475–531.
38. T. Shono, Y. Matsumura, K. Tsubata et al., 63. F. G. Bordwell, J.-P. Cheng, J. Am. Chem.
J. Org. Chem. 1989, 54, 2249–2251. Soc. 1991, 113, 1736–1743.
39. J.-S. Do, T.-C. Chou, J. Appl. Electrochem. 64. A. Rieker, R. Beisswenger, K. Regier, Tetra-
1992, 22, 966–972. hedron 1991, 47, 645–654.
40. J.-S. Do, Y.-L. Do, Electrochim. Acta 1994, 65. K. Fujimoto, H. Maekawa, A. Yamaguchi
39, 2037–2044. et al., Denki Kagaku 1994, 62, 1165–1168.
41. J.-S. Do, Y.-L. Do, Electrochim. Acta 1994, 66. H. J. Schäfer in Organic Electrochemistry
39, 2299–2309. (Eds.: H. Lund, M. M. Baizer), 3rd ed., Mar-
42. J. E. Leonard, P. C. Scholl, T. P. Steckel cel Dekker, New York, 1991, pp. 949–1027,
et al., Tetrahedron Lett. 1980, 21, 4695–4698. Chap. 23.
43. T. Shono, Y. Matsumura, M. Mizoguchi 67. Y. Kashiwagi, H. Ono, T. Osa, Chem. Lett.
et al., Tetrahedron Lett. 1979, 3861–3864. 1993, 81–84.
44. Y. Matsumura, M. Yamada, N. Kise et al., 68. M. Takahashi, H. Konishi, S. Iida et al.,
Tetrahedron 1995, 51, 6411–6418. Tetrahedron 1999, 55, 5295–5302.
45. T. Shono, Y. Matsumura, J. Hayashi et al., 69. G. M. Morrow, Y. Chen, J. S. Swenton,
Tetrahedron Lett. 1980, 21, 1867–1870. Tetrahedron Lett. 1991, 47, 655–664.
70. J. S. Swenton, K. Carpenter, Y. Chen et al., 96. S. Torii, H. Tanaka in Organic Electrochem-
J. Org. Chem. 1993, 58, 3308–3316. istry (Eds.: H. Lund, M. M. Baizer), 3rd
71. J. S. Swenton, A. Callinan, Y. Chen et al., J. ed., Marcel Dekker, New York, 1991,
Org. Chem. 1996, 61, 1267–1274. pp. 535–579, Chap. 14.
72. S. Yamamura, Y. Shizuri, H. Shigemori 97. H. Hofer, M. Moest, Justus Liebigs Ann.
et al., Tetrahedron 1991, 47, 635–644. Chem. 1902, 323, 284–328.
73. S. Maki, N. Asaba, S. Kasemura et al., Tetra- 98. H. J. Schäfer, S. Kratschmer, A. Weiper
hedron Lett. 1992, 33, 4169–4172. et al. in Novel Trends in Electroorganic
74. S. Maki, S. Kosemura, S. Yamamura et al., Synthesis (Ed.: S. Torii), Springer-Verlag,
Chem. Lett. 1992, 651–654. Tokyo, 1998, pp. 187–190.
75. S. Maki, K. Tomoda, S. Kosemura et al., 99. T. Kubota, Rep. Asahi Glass Found. 1991, 59,
Chem. Lett. 1993, 1059–1062. 307–313.
76. S. Maki, S. Kosemura, S. Yamamura et al., 100. T. Kubota, R. Aoyagi, H. Sando et al., Chem.
Tetrahedron Lett. 1993, 34, 6083–6086. Lett. 1987, 1435–1438.
77. K. Chiba, M. Jinno, R. Kuramoto et al., 101. N. Muller, Tetrahedron 1991, 47, 549–553.
Tetrahedron Lett. 1998, 39, 5527–5530. 102. R. N. Renaud, P. J. Champagne, M. Savard,
78. K. Chiba, M. Fukuda, S. Kim et al., J. Org. Can. J. Chem. 1979, 57, 2617–2620.
Chem. 1999, 64, 7654–7656. 103. C. J. Brookes, P. L. Coe, D. M. Owen et al.,
79. J. Y. Becker, L. L. Miller, T. M. Siegel, J. J. Chem. Soc., Chem. Commun. 1974, 323,
Am. Chem. Soc. 1975, 97, 849–853. 324.
80. F. Barba, A. Guirado, M. L. Segura et al., 104. R. N. Renaud, P. J. Champagne, Can. J.
An. Quim. 1979, 75, 967–969. Chem. 1975, 53, 529–534.
81. S.-Q. Chen, T. Hatakeyama, T. Fukuhara
105. W. Dmowski, A. Biernacki, T. Kozowski
et al., Electrochim. Acta 1997, 42, 1951–1960.
et al., Tetrahedron 1997, 53, 4437–4440.
82. J. Y. Becker, L. R. Byrd, L. L. Miller et al., J.
106. R. N. Renaud, P. J. Champagne, Can. J.
Am. Chem. Soc. 1975, 97, 853–856.
Chem. 1979, 57, 990–993.
83. C. B. Campbell, D. Pletcher, Electrochim.
107. P. J. Champagne, R. N. Renaud, Can. J.
Acta 1978, 23, 923–927.
Chem. 1980, 58, 1101–1105.
84. F. Barba, A. Guirado, A. Soler, An. Quim.
108. W. Dmowski, T. Kozowski, J. Fluorine
1979, 75, 404–407.
Chem. 1998, 87, 179–183.
85. S. Ye, F. Beck, Tetrahedron 1991, 47,
5463–5470. 109. L. Becking, H. J. Schäfer, Tetrahedron Lett.
86. T. Shono, Y. Matsumura, J. Hayashi et al., 1988, 29, 2797–2800.
J. Org. Chem. 1985, 50, 4967–4969. 110. K. Uneyama, Tetrahedron 1991, 47, 555–562.
87. P. Mattei, F. Diederich, Helv. Chim. Acta 111. A. Matzeit, H. J. Schäfer in Novel Trends
1997, 80, 1555–1588. in Electroorganic Synthesis (Ed.: S. Torii),
88. T. Shono, Y. Matsumura, K. Inoue et al., J. Kodansha, Tokyo, 1995, pp. 303–306.
Chem. Soc., Perkin Trans 1 1986, 73–77. 112. S. Torii, T. Inokuchi, Bull. Chem. Soc. Jpn.
89. F. Barba, M. N. Elinson, J. Escudero et al., 1976, 49, 771–774.
Electrochim. Acta 1998, 43, 973–976. 113. T. Shono, J. Hayashi, H. Omoto et al.,
90. F. Barba, M. N. Elinson, J. Escudero et al., Tetrahedron Lett. 1977, 2667–2670.
Tetrahedron Lett. 1996, 37, 5759–5762. 114. E. J. Corey, R. R. Sauers, J. Am. Chem. Soc.
91. T. Shono, Y. Matsumura, J. Hayashi et al., 1959, 81, 1739–1745.
Acta Chem. Scand. 1983, B37, 491–498. 115. T. Akiyama, T. Fujii, H. Ishiwari et al.,
92. T. Shono, Y. Matsumura, S. Katoh et al., Tetrahedron Lett. 1978, 2165, 2166.
Tetrahedron Lett. 1989, 30, 371–374. 116. H. H. Westberg, H. J. Dauben Jr., Tetrahe-
93. H. Kolbe, Ann. Chem. Pharm. 1849, 69, dron Lett. 1968, 5123–5126.
257–294. 117. D. Hermeling, H. J. Schäfer, Chem. Ber.
94. A. J. Fry, Synthetic Organic Electrochem- 1988, 121, 1151–1158.
istry, Harper & Row, New York, 1972, 118. C. B. Warren, J. J. Bloomfield, J. Org. Chem.
pp. 273–286. 1973, 38, 4011–4016.
95. H. J. Schäfer, Top. Curr. Chem. 1990, 152, 119. J. Nokami, T. Yamamoto, M. Kawada et al.,
91–151. Tetrahedron Lett. 1979, 1047, 1048.
120. I. Kitagawa, M. Yoshikawa, T. Kamigauchi 128. H. Yamazaki, H. Horikawa, T. Nishitani

et al., Chem. Pharm. Bull. 1981, 29, et al., Tetrahedron 1991, 47, 541–548.
2571–2581. 129. Y. Matsumura, Y. Shirakawa, Y. Satoh et al.,
121. T. Iwasaki, H. Horikawa, K. Matsumoto Org. Lett. 2000, 2, 1689–1691.
et al., J. Org. Chem. 1979, 44, 1552–1554. 130. J. Nokami, M. Kawada, R. Okawara et al.,
122. D. Seebach, R. Charczuk, C. Gerber et al., Tetrahedron Lett. 1979, 1045, 1046.
Helv. Chim. Acta 1989, 72, 401–425. 131. T. Shono, Y. Matsumura, S. Yamane et al.,
123. M. Mori, K. Kagechika, H. Sasai et al., Chem. Lett. 1982, 565–568.
Tetrahedron 1991, 47, 531–540. 132. Y. Matsumura, T. Maki, Y. Satoh, Tetrahe-
124. P. Renaud, D. Seebach, Angew. Chem. Int. dron Lett. 1997, 38, 8879–8882.
Ed. Engl. 1986, 25, 843–845. 133. Y. Matsumura, Y. Satoh, T. Maki et al.,
125. P. Renaud, D. Seebach, Helv. Chim. Acta Electrochim. Acta 2000, 45, 3011–3020.
1986, 69, 1704–1710. 134. Y. Matsumura, Y. Satoh, K. Shirai et al.,
126. A. Zietlow, E. Steckhan, J. Org. Chem. 1994, J. Chem. Soc., Perkin Trans. 1 1999,
59, 5658–5661. 2057–2060.
127. C. Herborn, A. Zietlow, E. Steckhan, Angew.
Chem., Int. Ed. Engl. 1989, 28, 1399–1401.
199
7
Reduction of Oxygen-containing
Compounds
Shigenori Kashimura and Manabu Ishifune

Kin-Ki University, Osaka, Japan
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201

7.2 Cathodic Reduction of Alcohols . . . . . . . . . . . . . . . . . . . . . . . . . 201
7.3 Cathodic Reduction of Ethers . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
7.4 Cathodic Reduction of Esters and Amides . . . . . . . . . . . . . . . . . . 203
7.5 Cathodic Reduction of Carboxylic Acid . . . . . . . . . . . . . . . . . . . . 207
7.6 Cathodic Reduction of Ketones, Aldehydes, and Carbon Dioxide . . . 209
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
201
7.1 can be electrochemically reduced under

Introduction mild reaction conditions.
Numerous studies concerning the elec-
This chapter is concerned with the electroreduction of oxygen-containing com-
troreduction of oxygen-containing compounds have been reported so far and
pounds, that is, the cathodic reduction of our knowledge in this field is far from
alcohols, ethers, esters, amides, carboxylic complete. However, previous studies in
acids, aldehydes, and ketones. The reduc- this area until 1990, have been well sum-
tion potentials of these oxygen-containing marized in the literature [1–3]. Thus, this
compounds depend highly on their struc- chapter mainly deals with studies after
tures. In general, oxygen-containing aro- 1990 along with some typical examples
matic compounds are rather easily elec- reported until 1990. In addition, many
troreducible because aryl groups act as studies in this field have been carried out
electron-withdrawing substituents and fa- from both the synthetic and mechanistic
cilitate the electron transfer from the point of view; however, the main con-
cathode to the substrates. The electrore- tents of this chapter focus on the modern
duction of aliphatic ketones and alde- synthetic reactions using electrochemical
hydes has long been known and has reduction.
been well established from the synthetic
and mechanistic viewpoints [1–3], because
these compounds are electrochemically re- 7.2
ducible under mild reaction conditions. Cathodic Reduction of Alcohols
On the other hand, the reduction poten-
tials of other oxygen-containing aliphatic Cleavage of C−O bonds by direct elec-
compounds such as aliphatic alcohols, tron transfer from a cathode is usually
ethers, carboxylic acids, and esters are difficult because of the negative reduc-
highly negative and their electroreduction tion potential of the bond. Therefore,
has proved to be difficult until recently. In the reduction of aliphatic alcohols (R-
the last few years, some new electroreduc- OH) to the corresponding hydrocarbons
tive methods, which enable reduction of (R-H) is often carried out by the trans-
alcohols, aliphatic esters, and carboxylic formation of hydroxyl groups to good
acids, have been reported and now al- leaving groups such as halides (X =
most all oxygen-containing compounds Br, I), methanesulfonates (OMs), and
202 7 Reduction of Oxygen-containing Compounds
p-toluenesulfonates (OTs) followed by reliable methods for the reduction of

electroreduction (Scheme 1) [4, 5]. The de- alcohols to the corresponding hydro-
tails of the electroreduction of halides carbons. In this reaction, the role of
are given in Chapter 8 (oxidation and the anode and the cathode is as fol-
reduction of halogen-containing com- lows: trialkyl phosphine is anodically ox-
pounds) and that of methanesulfonates idized to the corresponding cation rad-
and p-toluenesulfonates is summarized ical, which reacts with the alcohol to
in Chapter 9 (electrochemistry of sulfur- form a phosphonium salt. The elec-
containing compounds). troreduction of the phosphonium salt
Aromatic hydroxyl groups are also dif- leads to the formation of a hydrocarbon
ficult to reduce; however, the transfor- (Scheme 4) [10, 11].
mation of hydroxyl groups to phospho- The cleavage of C−O bonds un-
nate esters followed by electroreduction der usual conditions of electroreduc-
affords the corresponding hydrocarbons tion is rather difficult. However, 1,2-
(Scheme 2) [6]. elimination and 1,3-elimination of hy-
Although the electroreduction of nonac- droxyl groups initiated by the elec-
tivated alcohols requires appropriate acti- tron transfer to neighboring groups
vation of hydroxyl groups as mentioned such as SPh, SO2 Ph takes place un-
above, activated ones such as allylic and der mild reaction conditions and leads
benzylic alcohols can be reduced by direct to the cleavage of C−O bonds. Usu-
electroreduction (Scheme 3) [1, 7–9]. ally, 1,2-elimination needs no activa-
Electrolysis of alcohols in an undivided tion of the hydroxyl group (Scheme 5),
cell and in the presence of trialkyl whilst for 1,3-elimination, an appropriate
phosphine is recently reported, and activation of the hydroxyl group is required
this is one of the most simple and (Scheme 6) [12–14].
+e
R OH R X R H
X = Br, I, OMs, OTs
Scheme 1 Cathodic desoxygenation of aliphatic alcohols; yields, e.g. for X = OMs: 63–85%.
+e
Ar OH Ar OPO(OEt)2 Ar H
Scheme 2 Cathodic desoxygenation of phenols; yields: in general, 40–70%.
+e
R1CH2 OH R1CH2 H
R = Ar, R CH
1 2
CH
Scheme 3 Cathodic desoxygenation of allylic and benzylic alcohols via in situ formed iodides; yields:
up to 95%.
−e +e
R3P R3P+ O R′ R′ H
R′ OH
Scheme 4 Cathodic desoxygenation of alcohols via phosphonium salts; R : aliphatic, benzylic, yields:
48–96%.
7.4 Cathodic Reduction of Esters and Amides 203
R1 R1
+e
R3 R3 Y = SPh, SO2Ph
Y
R2 OH R2
Scheme 5 Cathodic 1,2-elimination of β-arylthio- and β-arylsulfonyl-substituted alcohols; R1 , R2 , R3 :

aliphatic, H, yields: 50–96%.
R1 R1 1R
+e Y = SPh
R2 OH R2 X X = OMs, OTs
Y Y R2
Scheme 6 Cathodic 1,3-elimination of γ -substituted alcohols; R1 , R2 : aliphatic, H, yields: 65–75%.
7.3 7.4
Cathodic Reduction of Ethers Cathodic Reduction of Esters and Amides
Because the reduction potential of ether Electroreduction of esters (R1 COOR2 ) is

is usually more negative than that of classified into three types of reaction.
halides, examples that belong to this The first type of reaction is the reductive
category are rather rare. Generally, ca- cleavage of a bond between oxygen and
thodic reduction of ethers is similar to R2 . This type of reaction is similar
that of alcohols, and nonactivated ethers to the cathodic reduction of alcohols
are not reducible under the conditions (Sect. 7.2) and ethers (Sect. 7.3). That is,
of electroreduction. Activated ethers such activated esters such as allylic and benzylic
as benzylic and allylic ethers are elec- esters are electrochemically reduced to
trochemically reduced to a limited ex- the corresponding hydrocarbons and acids
tent (Scheme 7) [1, 15, 16]. Reduction (Scheme 8) [1, 16, 19–21].
of epoxides is usually difficult; however, Cathodic 1,2-elimination of activated
electroreductive cleavage of activated epox- esters leads to the cleavage of the C−O
ides to the corresponding alcohols is bond and this method is useful for the
reported [17, 18]. The cleavage of the deprotection of protected carboxyl groups
C−O bond of ethers is more easily ac- (Scheme 9) [22, 23].
complished in anodic oxidation than in The second type of reaction is the
cathodic reduction, which is stated in reductive coupling of α, β-unsaturated es-
Chapter 6. ters. These reactions are well documented
+e
R1CH2 OR2 R1CH2 H
R1 = Ar, R 3CH CH
Scheme 7 Cathodic cleavage of benzyl ethers.
+e
RCH2 OCOCH3 RCH2 H + CH3CO2H
R = Ar, R 1CH CH
Scheme 8 Cathodic cleavage of benzyl- and allylesters; e.g. benzyl carbamate, yields: 90–99%.
+e
RCOOCH2CCl3 RCOOH
Scheme 9 Cathodic deprotection of esters; R: phenyl, phenylNH, benzyl, polyene, yields: 45–90%.
COOMe
R R
+e COOMe Base
2 COOMe O
R COOMe R
R
Scheme 10 Intermolecular cathodic coupling of α,β-unsaturated esters; R: subst. phenyl, yields:
50–60%.
COOMe +e COOMe
(CH2)n (CH2)n
COOMe n = 1 − 4 COOMe
Scheme 11 Intramolecular cathodic coupling of α,β-unsaturated esters; yields: 40–100%.
in the literature [1], and hence, typi- A third type of reaction is the reduc-
cal examples of intermolecular and in- tion of the C=O bond of esters. Until
tramolecular coupling reactions are ex- recently, electroreduction of esters to the
emplified in Schemes 10 and 11, respec- corresponding alcohols has been limited
tively [24, 25]. to that of aromatic compounds as shown
α, β-Unsaturated amides show similar in Scheme 13 [1, 29, 30].
reactivities as the corresponding esters. Electroreduction of aromatic esters to
For example, electroreduction of chiral the corresponding aldehydes is accom-
α, β-unsaturated amides affords chiral- plished by the reduction of esters in the
coupling products in partially high di- presence of chlorotrimethylsilane (CTMS)
astereoselectivity (Scheme 12) [26–28]. (Scheme 14) [31].
COY COY O
O Ar 3S 2R Ar 3R 2S
+e
O + O Y= N O
Ar Y
Ar 4R Ar 4S i-Pr
Scheme 12 Diastereoselective intermolecular cathodic coupling of α,β-unsaturated esters; yields:
70–98%, de: 0 to >95%.
+e
COOR CH2OH
X X
Scheme 13 Cathodic reduction of aromatic esters to benzyl alcohols; e.g. X: 3-OH, yield: 91.5%.
+e
COOR CHO
CTMS
X X
Scheme 14 Cathodic reduction of aromatic esters to aromatic aldehydes; X = H, alkyl, yields: 0–70%.
7.4 Cathodic Reduction of Esters and Amides 205
Because of the highly negative reduc- aliphatic esters with the Mg electrode is
tion potentials (∼ −3.0 V vs. SCE) [32], performed in the presence of t-BuOH as a
the electroreduction of esters of aliphatic proton source, the corresponding primary
carboxylic acids to primary alcohols by di- alcohols are obtained in high yield. The
rect electron transfer from the cathode use of t-BuOD instead of t-BuOH yielded
is very difficult and the electrochemical deuterated alcohols with high deuterium
Birch-type reduction of aliphatic esters incorporation (Scheme 16).
in MeNH2 or liquid NH3 has not been This method is also applicable to the
reported until recently (Scheme 15) [33, reduction of amides to the corresponding
34]. This reaction is not a reduction aldehydes and alcohols by controlling
by direct electron transfer from the the amount of t-BuOH and supplied
cathode to the C=O bonds of the es- electricity. The reduction in the presence
ter but the reduction by a solvated of t-BuOD gives deuterated aldehydes
electron. (Scheme 17).
Electroreduction of aliphatic esters has Electroreduction of aliphatic esters
been recently achieved by using a Mg with an Mg electrode, under apro-
electrode [35]. When the reduction of tic conditions, leads to dimerization
+e
RCOOMe RCH2OH
MeNH2, LiCl
Scheme 15 Cathodic Birch-type reduction of aliphatic esters to alcohols; R: alkyl, yields: 95%.
O−
+e +e
RCOOMe R • OMe RCY2OY
Mg electrode t-BuOY
Y = H or D
Scheme 16 Deuterated alcohols by cathodic reduction in the presence of t-BuOD.
+e, t-BuOH (7 equiv.)

Ph(CH2)2CH2OH
THF/LiClO4
Mg cathode and anode
+e, t-BuOH (3.5 equiv.)

Ph(CH2)2CONMe2 Ph(CH2)2CHO
THF/LiClO4
Mg cathode and anode
+e, t-BuOD (3.5 equiv.)

Ph(CH2)2CDO
THF/LiClO4
Mg cathode and anode Degree of deuterium
incorporation: 72%
Scheme 17 Cathodic reduction of amides to alcohols and aldehydes; yields (alcohol): 70–82%,
yields (aldehyde): 65%.
affording the corresponding 1,2-diketone Although electroreduction of a mixture

whereas a bis-(trimethylsilyloxy)alkene is of esters with an Mg electrode gives a
obtained on reduction in the presence mixture of symmetrical and unsymmet-
of chlorotrimethylsilane (Scheme 18) [36]. rical 1,2-diketones (Scheme 19), the re-
Electroreduction of aromatic esters un- duction of diesters affords unsymmetrical
der aprotic conditions leads to the 1,2-diketones as the single product
corresponding 1,2-diketones [37]. The cru- (Scheme 20) [38, 39]. The selectivity of the
cial factor in generating the 1,2-diketone reaction shown in Scheme 20 is highly de-
is the formation of the Mg salt that is pendent on the value of n and the best
insoluble in the solvent (THF). result is obtained when n = 2.
+e O−
RCOOMe
Mg electrode •
R OMe
Mg2+ O
R
O − O− R
R O
R
OMeOMe OSiMe3
+e CTMS R
R
Mg electrode
OSiMe3
Scheme 18 Cathodic dimerization of esters to 1,2-diketones; R: alkyl, aryl; yields (diketone):

33–65%, yields (endioldiether): 55–78%.
+e 5F mol−1
C3H7CO2Me + C5H11CO2Me
THF/LiClO4
Mg electrode
O O
O
C5H11
C3H7 + C5H11
C5H11 + C3H7
C3H7
O O
O
16% 19% 29%
Scheme 19 Symmetrical and unsymmetrical 1,2-diketones from mixtures of esters.
O
+e
R2
n=2 THF/LiClO4 R1
Mg electrode O
R1COO (CH2)n OCOR2 O O
O
n = 2–4 R2 + R2
n = 3, 4 +e R1 + R2
R1 R1
THF/LiClO4 O
O O
Mg electrode
Scheme 20 Selectivity of unsymmetrical 1,2-diketone formation from unsymmetrical diesters of

1,n-diols.
7.5 Cathodic Reduction of Carboxylic Acid 207
The anion radical species formed by the 7.5

electroreduction of aliphatic esters show Cathodic Reduction of Carboxylic Acid
interesting reactivities, and the reduction
of olefinic esters gives bicyclic products Electroreduction of aromatic carboxylic
with high regio- and stereoselectivity. acid to the corresponding aldehydes and al-
cohols has been well studied [1], however,
The electroreduction of the ester in the
examples of the reduction of aliphatic
presence of chlorotrimethylsilane affords
carboxylic acids are rare. The aromatic
a tricyclic product (Scheme 21) [35, 40].
carboxylic acids are usually reduced to
The mechanism of this cyclization reaction
the corresponding benzylic alcohols un-
seems to be the addition of anion radical
der acidic conditions (Scheme 23) [42–46].
species, formed by the reduction of Substitution of an electron-withdrawing
the ester group, to the carbon–carbon group on the aromatic ring further fa-
double bond. cilitates the electron transfer from the
Electroreduction of aliphatic amides in cathode to the carboxyl group. Selectivity
the presence of chlorotrimethylsilane gives of electroreduction of aromatic carboxylic
coupling products and this reaction is acids to the corresponding aldehydes
useful for the synthesis of α-amino ketones can be achieved by controlling the reac-
(Scheme 22) [41]. In this reaction, the tion medium [47].
formation of an Mg salt promotes the Although some electroreduction of
coupling of two anion radical centers. aliphatic acids are reported in the older
+e
Mg electrodes
CO2Me
+e, t-BuOH
Me
• OH
•
O− O−
MeO MeO +e, THSCl
TMSO
Scheme 21 Cathodic cyclization of unsaturated esters; yield (alcohol): 60%, yield (TMS ether): 67%.
O Mg
+e (3 F mol−1), THSCl O− O O
2 R1 2
NR2 LiClO4 / THF • •
Mg electrode R1 • NR2 R1 R
NR2 NR2 1
NR2 O NR2
10% HCl
R1
R1
R1 R1
TMSO
Scheme 22 Cathodic coupling of amides; R1 : alkyl, R2 : methyl, yields: 63–70%.

CH2OH
COOH
+e
Y CHO
Y
Scheme 23 Cathodic reduction of aromatic carboxylic acids to benzyl alcohols or benzaldehydes.
literature [48], the yields are very low. Elec- acids gives acyl anion equivalents. The
troreduction of aliphatic carboxylic acids hydrolysis of the anion yields the cor-
under usual anhydrous reaction condi- responding aldehyde, and the reaction
tions does not lead to electron transfer to of the anion with alkyl halide fol-
the C=O group but leads to a deprotona- lowed by hydrolysis affords a ketone
tion reaction through the reduction of the (Scheme 25) [50, 51].
proton. This deprotonation reaction can be Recently, the electrolysis of aliphatic
applied to the preparation of esters under carboxylic acids in an undivided cell and
mild reaction conditions (Scheme 24) [49]. in the presence of triphenyl phosphine
Appropriate activation of carboxyl has been reported, which turned out to
groups enables reduction of aliphatic carbe one of the most reliable methods
boxylic acids to the corresponding alde- for the reduction of aliphatic carboxylic
hydes. The electroreduction of iminium acids to the corresponding aldehydes
salts prepared from aliphatic carboxylic (Scheme 26) [11, 52]. In this reaction,
+e
RCOOH RCOO− R4N+ R′-X RCOOR′
R4N+
Scheme 24 Cathodic alkylation of carboxylic acids to esters; R: alkyl, aryl, R : alkyl, yields: 24–96%.
Me Me H3O+
RCHO
I− N N
H2N OH
R + +e R −
RCOOH
Me-I O
O
R′-X
RCOR′
H3O+
Scheme 25 Cathodic reduction of activated aliphatic carboxylic acids to aldehydes (R: alkyl, yields:
70–82%) and ketones (R : benzyl, yields: 66 – 72%).
−e Ph3P, +e O− +e
R3P +
R3P O COR′ + R′ CHO
R′-COOH R′ • PR3 H+
Scheme 26 Cathodic reduction of aliphatic carboxylic acids in the presence of triphenylphosphine to

aldehydes; R : alkyl, aryl, yields: 36 – 100%.
7.6 Cathodic Reduction of Ketones, Aldehydes, and Carbon Dioxide 209
triphenyl phosphine is anodically oxidized of the products often depends on the re-
to the corresponding cation radical, which action conditions. The mechanism of the
reacts with carboxylic acids to form electroreduction of ketones and aldehy-
acyl phosphonium salts. These salts are des is similar to that of esters though the
electroreduced to aldehydes. reduction potentials of esters are much
This reaction is applicable to the re- more negative than those of ketones. One
duction of α-amino acids to optically electron transfer from the cathode to the
active α-amino aldehydes with high yields substrates forms anion radical species.
(Scheme 27) [53]. The fate of the anion radical depends on
The acyl radical equivalents formed by the reaction conditions and radical cou-
the electroreduction of acyl phosphonium pling products are often formed under
salts have an interesting reactivity and the aprotic conditions [1, 56, 57], while fur-
electroreduction of nonconjugated olefinic ther reduction of the anion radical to the
acids yields intramolecular coupling prod- corresponding alcohols takes place under
ucts (Scheme 28) [11, 54, 55]. protic conditions (Scheme 29) [1, 58–61].
Since the electroreduction of ketones
shown in Scheme 29 has been well es-
7.6 tablished [1–3, 12, 62–65], one more
Cathodic Reduction of Ketones, Aldehydes, recent interest in the electroreduction
and Carbon Dioxide of carbonyl compounds is focused on
the stereo-selective reduction of ketones.
Reduction potentials of ketones and For example, the diastereo-selective ca-
aldehydes are effected by the sub- thodic coupling of aromatic ketones
stituents. Electron-withdrawing groups has been reported. In the presence of
usually facilitate the electroreduction of a chiral-supporting electrolyte, a low
these compounds [1, 2]. Electroreduction degree of enantioselectivity has been
of aliphatic and aromatic ketones and alde- found [66] (Scheme 30).
hydes generally takes place under mild Electroreduction of carbonyl compounds
reaction conditions; however, the nature under irradiation of ultrasound is another
H NHCbz −e/+e H NHCbz
R COOH Ph3P, CH 2Cl2 R CHO
Scheme 27 Cathodic reduction of amino acids in the presence of triphenylphosphine to amino

aldehydes; R: alkyl, yields: 81–84%.
R1 O− O R1
+e • PBu3 +e
R2 n COOH R1 R2
Bu3P, CH 2Cl2
n
n R2
n = 1, 2
Scheme 28 Cathodic cyclization of unsaturated acids in the presence of triphenyl phosphine; R1 :
alkyl, H, aryl, R2 : H, aryl, yields: 11–49%.
HO OH
1, aprotic
R R R
+e R 2, H+ R′ R′
O −
• O
R′ R′ +e R
H OH
H+
R′
Scheme 29 Cathodic reduction of ketones; diols R1 : aryl, R2 : H, yields: in general 45–100%;

alcohols: R1 , R2 : alkyl, yields: in general, 45–100%.
HO OH
Ar Ar
+e
O • O− Ar *
*
Ar
Me Me Me
Me
Scheme 30 Diastereoselective cathodic coupling of aromatic ketones in the presence of chiral
supporting electrolyte, yield: 91%, 25% ee.
new technique of electrochemistry. For in- anion radical species may act as an electro-
stance, electroreductive-coupling reactions generated base (EGB) (details of EGB are
under ultrasonic irradiation remarkably shown in Chapter 14) and promotes the
increase the selectivity of the coupling base-catalyzed condensation reaction of ke-
(Scheme 31) [67]. tones and aldehydes (Scheme 33) [71–73].
Asymmetric electroreduction of ketones In another case, the anion radical species
to the corresponding chiral alcohols has undergoes regio- and stereoselective in-
recently been reported. Typical examples termolecular coupling reactions with car-
are the reduction of ketones bearing bon–carbon double bonds (Scheme 34) or
chiral auxiliaries [68, 69], and the indi- triple bonds [74]. This reaction is useful for
rect reduction of ketones with alcohol the regio- and stereo-selective formation
dehydrogenase (ADH), as a mediator of cyclic alcohols having a 5-membered
(Scheme 32) [70]. ring [75, 76].
Anion radical species formed by elec- The radical cyclization reaction shown
troreduction of carbonyl compounds show in Scheme 34 exclusively takes place at
interesting reactivities. In some cases, the the higher substituted carbon atom of the
Ar HO OH Ar
+e
O Ar Ar + OH
Me Me Me Me
Scheme 31 Influence of sonication on the selectivity in the cathodic reduction of aromatic ketones:
diol 10–23% (without sonication), 36–42% (with sonication).
R2 R2
+e
O * OH
ADH
R1 R1
Scheme 32 Electroenzymatic reduction of ketones with alcohol dehydrogenase; R1 : aryl, R2 : alkyl,
CHO, CO2 H, yields: 92–100%, 0 – 100% ee.
+e −•
RCH2CHO RCH2CHO
−•
RCH2CHO
−
RCH2CHO RCHCHO
−
RCHCHO
RCH2CHO RCH2CH CCHO
−• R
RCH2CHO EGB
Scheme 33 Base catalyzed condensation of aldehydes by electrogenerated bases (EGB’s); R: alkyl,

yields: 72–77%, very high current efficiency.
O R O− R OH
+e • 1) +e Me
R
DMF/Et4NOTs 2) H3O+
Scheme 34 Cathodic cyclization of unsaturated ketones; R: alkyl, yields: 75–98%.
double bond and forms a 5-membered The anion radical species also adds to
ring, whilst the similar cyclization reaction a carbon nitrogen triple bond and affords
to the silyl substituted carbon–carbon cyclic ketones (Scheme 37) [79, 80].
double bond predominantly occurs at the In contrast to the high regioselectivity
lower substituted carbon atom of the and good yields of electroreductive in-
double bond and forms a 6-membered ring tramolecular coupling reactions of ketones
(Scheme 35) [77]. with multiple bonds shown in Schemes 34
The addition of cathodically generated to 37, the yields of intermolecular coupling
butyl radicals to aromatic rings forms reactions have been very low until recently.
cyclic alcohols with high stereoselectivity However, by using carbon fiber electrodes,
(Scheme 36) [78]. intermolecular coupling reactions have
Me O Me O Me OH
O SiMe3
•
+e
Me •
SiMe3 SiMe3
SiMe3
Scheme 35 Intramolecular cathodic coupling of vinylsilanes with ketones; yields: 55%.
O O−
R OH
R •
+e R
i-PrOH
Scheme 36 Intramolecular cathodic cyclization of ketones with aryl rings; R: alkyl, yields: 21–74%.
O O− O
CN CN HO
n n
+e •
n
i-PrOH
Scheme 37 Intramolecular cathodic cyclization of ketones with nitriles; n: 1,2, yields: 55–76%.
O R2
+e
R1 R2 + R3 Carbon fiber electrode R
1 R3
OH
Scheme 38 Cathodic intermolecular coupling of ketones with alkenes; R1 , R2 , R3 : alkyl, yield:

52–82%.
now attained in reasonable yields (∼80%) of acetone with cis-(R)-2-octen-4-ol gave

(Scheme 38) [81]. (3R,5R)-2,3-dimethyl-2,5-nonanediol with
In the cathodic intermolecular coupling high diastereoselectivity.
of ketones with optically active allylic Electroreductive coupling of ketones
alcohols, the hydroxyl group plays an with silyl-substituted olefins promotes in-
important role in promoting the stereo- teresting reactions that are useful for
selective coupling reaction, and the forma- organic synthesis. For example, coupling
tion of a cyclic intermediate is suggested of ketones with trimethylvinylsilanes af-
to be the reason for a high diastereos- fords β-trimethylsilyl alcohols, which are
electivity (de = ∼95%) (Scheme 39) [82]. easily transformed to the corresponding
For example, the cathodic coupling olefins (Scheme 40). This reaction is in-
of acetone (R1 = R2 = CH3 ) with teresting from the synthetic point of view
trans-(R)-2-octen-4-ol (R3 = CH3 , R4 = since vinylsilane behaves as the equivalent
R5 = H, R6 = C4 H5 ) and trans-(R)-5- to a β-trimethylsilyl group-substituted
methyl-2-hexen-4-ol (R3 = CH3 , R4 = anion [77, 83].
H, R5 = CH3 , R6 = C2 H5 ) gave the Cathodic coupling of ketones with
corresponding (3S,5R)-2,3-dimethyl-2,5- an ethoxydimethylsilyl-substituted olefin
nonanediol and (3S,5R)-2,3,6-trimethyl- affords oxasilacyclopentanes with excel-
2,5-heptanediol, respectively, with excellent yield. This coupling is synthetically
lent diastereoselectivity. Also, the coupling valuable as the coupling product is a
O +e O-
•
R1 R2 R1 R2
OH R1
* −
R1 O H R1 O− H OH
R3 5 R6
2
R2 OH
R4 R R O +e R2 O H3O+
*
• * − * R3 *
R3 R3 R6 R6
R6 R5
R5 R4 R
5
R4
R4
Scheme 39 Diastereoselective cathodic coupling of ketones with allylic alcohols; yields: 60–90%.
OH
O R3 R1 R1 R3
+e R3 BF3 • HOAc R3
+ −
R1 R2 SiMe3 SiMe3
SiMe3
R2 R2
Scheme 40 Cathodic intermolecular coupling of ketones with vinyl trimethylsilane; R1 , R2 : alkyl, R3 :
prim. sec. alcohol, yields: 35–96%.
R3
Me 3
O R3 +e R1 30% H2O2 R1 OH R
Si
+ O OH
R1 R2 Si(OEt)Me2 R2 NaHCO3 R2
Me
R3 R3
Si(OEt)Me2 OH
Scheme 41 Cathodic intermolecular coupling of ketones with vinyl ethoxy dimethylsilane; R1 , R2 :

alkyl, R3 : H, alkyl, yields: 62–79%.
useful key intermediate for the prepara- trimethylsilyl-substituted carbon of the

tion of a 1,3-diol. In this reaction, the double bond (Scheme 42) [77].
ethoxydimethylsilyl-substituted olefin acts Anion radical species formed by the
as the equivalent of a β-hydroxy substituted electroreduction of ketones also inter-
anion (Scheme 41) [84]. molecularily add to a carbon–nitrogen
The existence of a trimethylsilyl double bond and form derivatives of an
group on the carbon–carbon double α-amino alcohol (Scheme 43) [85].
bond seems to activate the double Carbon dioxide (CO2 ) is another re-
bond towards radical addition since the ducible species with a carbon–oxygen
electroreductive intermolecular coupling bond. The electroreduction of CO2 is well
of ketones with carbon–carbon double established in the literature [1], however,
bond predominantly takes place at the the nature of the product highly depends
O SiMe3 SiMe3
+e
+
HO
Scheme 42 Selectivity in the intermolecular coupling of ketones with vinyl trimethylsilanes; yields:
86%.
OMe
R2
O O− N
+e R1 C C
R1 R2 R1 • R2
HO NHOMe
Scheme 43 Intermolecular cathodic heterocoupling of ketones with oximes; R1 , R2 : alkyl, cycloalkyl,
yields: 43–98%.
on the reaction conditions. The forma- 18. T. Inokuchi, M. Kusumoto, T. Sugimoto

tion of formic acid, oxalic acid, glyoxylic et al., Phosphorus, Sulfur Silicon Relat. Elem.
1992, 67, 271–276.
acid, glycolic acids, carbon monooxide,
19. H. L. S. Maia, M. J. Mediros, M. I. Montene-
methanol, and ethylene glycol has been gro et al., J. Electroanal. Chem. 1986, 200,
reported so far. Recently metal catalysts 363–370.
effective for the reduction of carbon diox- 20. M. A. Casadei, D. Pletcher, Synthesis 1987,
ide have been reported. Typical examples 1118–1119.
are the reduction of carbon dioxide using 21. J. G. Gourcy, M. Hodler, B. Terem et al., J.
Chem. Soc., Chem. Commun. 1976, 779–780.
Co [86], Re [87], Ru [88], and Ni [89]. 22. M. F. Semmelhack, G. E. Heinsohn, J. Am.
Chem. Soc. 1972, 94, 5139, 5140.
References 23. T. W. Greene, P. G. M. Wuts, Protect-
ing Groups in Organic Synthesis, Wiley-
1. H. Lund, M. Baizer, Organic Electrochemistry, Interscience, New York, 1991.
Marcel Dekker, New York, 1991. 24. L. H. Klemm, D. R. Olson, J. Org. Chem.
2. D. H. Evans, Encyclopedia of Electrochemistry 1973, 33, 3390–3394.
of the Element, Marcel Dekker, New York, 25. J. P. Petrovich, J. D. Anderson, M. M. Baizer,
1978. J. Org. Chem. 1966, 31, 3897–3903.
3. M. R. Rifi, Technique of Electroorganic Syn- 26. N. Kise, S. Mashiba, N. Ueda, J. Org. Chem.
thesis, Part 2, Wiley-Interscience, New York, 1998, 63, 7931–7938.
1974. 27. J. H. P. Utley, M. Gullu, M. Motevalli, J.
4. G. M. McNamee, B. C. Willett, D. M. La Per- Chem. Soc., Perkin Trans. 1 1995, 1961–1973.
riere et al., J. Am. Chem. Soc. 1977, 99, 28. N. Kise, Y. Hirata, T. Hamaguchi et al.,
1831–1835. Tetrahedron Lett. 1999, 40, 8125–8128.
5. T. Shono, Y. Matsumura, K. Tsubata et al., 29. F. D. Popp, H. P. Schultz, Chem. Rev. 1962,
Tetrahedron Lett. 1979, 23, 2157–2160. 62, 19–42.
6. T. Shono, Y. Matsumura, K. Tsubata et al., J. 30. R. Oi, C. Shimakawa, Y. Takenaka, Bull.
Org. Chem. 1979, 44, 4508–4511. Chem. Soc. Jpn. 1987, 60, 4193–4195.
7. H. Lund, M. A. Michel, G. Mousset et al., 31. P. R. Goetz-Schatowitz, G. Struth, J. Voss
Electrochim. Acta 1974, 19, 629–633. et al., J. Prakt. Chem./Chem.-Ztg. 1993, 335,
8. G. Horanyi, Electrochim. Acta 1986, 31, 230–234.
1095–1103. 32. D. Belotti, J. Cossy, J. P. Pete et al., J. Org.
9. T. Lund, H. Lund, Acta Chem. Scand. 1984, Chem. 1986, 51, 4196–4200.
B38, 387–390. 33. R. A. Benkeser, H. Watanabe, S. J. Mels
10. H. Maeda, T. Maki, K. Eguchi et al., Tetrahe- et al., J. Org. Chem. 1970, 35, 1210–1216.
dron Lett. 1994, 35, 4129–4132. 34. J. C. Chaussard, A. Combellas, S. Thiebault,
11. H. Maeda, H. Ohmori, Acc. Chem. Res. 1999, Tetrahedron Lett. 1987, 28, 1173, 1174.
32, 72–80. 35. T. Shono, H. Masuda, H. Murase et al., J.
12. T. Shono, Y. Matsumura, S. Kashimura, Org. Chem. 1992, 57, 1061, 1062.
Chem. Lett. 1978, 69–72. 36. S. Kashimura, Y. Murai, H. Masuda et al.,
13. T. Shono, Y. Matsumura, S. Kashimura et al., Tetrahedron Lett. 1995, 36, 4805–4808.
Tetrahedron Lett. 1978, 2807–2810. 37. M. Heintz, M. Devaud, H. Hebri et al., Tetra-
14. T. Shono, Y. Matsumura, S. Kashimura et al., hedron 1993, 49, 2249–2252.
Tetrahedron Lett. 1978, 1205–1208. 38. S. Kashimura, M. Ishifune, H. Ishida et al.,
15. H. Lund in Organic Electrochemistry (Eds.: Nov. Trends Electroorg. Synth. (Ed.: S. Torii),
H. Lund, O. Hammerich), Marcel Dekker, Kodansha, Tokyo, 1995, 213–216.
New York, 2001, Chap. 23, p. 977. 39. S. Kashimura, Y. Murai, D. Yoshihara et al.,
16. V. G. Mairanovsky, Angew. Chem., Int. Ed. Tetrahedron Lett. 1997, 38, 6717–6720.
Engl. 1976, 15, 281–292. 40. S. Kashimura, Y. Murai, M. Ishifune et al.,
17. A. V. Kamernitskii, I. G. Reshetora, E. I. Acta Chem. Scand. 1999, 53, 949–951.
Chernoburova et al., Chem. Abstr. 1984, 111, 41. S. Kashimura, M. Ishifune, Y. Murai et al.,
62 512. Tetrahedron Lett. 1998, 39, 6199–6203.
42. L. Horner, H. Hönl, Liebigs Ann. Chem. 1977, 66. W. J. M. van Tilborg, C. J. Smit, Recl. Trav.
2036–2066. Chim. Pays-Bas 1979, 98, 532–536.
43. H. Lund, Acta Chem. Scand. 1963, 17, 67. M. Atobe, T. Tonoi, T. Nonaka, Electrochem.
972–978. Commun. 1999, 1, 593–596.
44. Conti Oil, US 35266581 (1970). 68. S. Marion, P. Susanne, H. C. Heinz, J. Elec-
45. Standard Oil, USP, 1983, 4381229. troanal. Chem. 1999, 461, 94–101.
46. Otsuka Chemicals, JP, 1983, 117887. 69. C. Reufer, C. Zielinski, H. J. Schafer et al.,
47. Sumitomo Chemicals, JP, 1981, 156782. Acta Chem. Scand. 1999, 53, 1023–1037.
48. S. Ohno, T. Hayashi, Bull. Chem. Soc. Jpn. 70. R. Yuan, S. Watanabe, S. Kuwabata et al., J.
1953, 26, 232–234. Org. Chem. 1997, 62, 2494–2499.
49. T. Awata, M. M. Baizer, T. Nonaka et al., 71. T. Shono, S. Kashimura, K. Ishizaki, Elec-
Chem. Lett. 1985, 371–374. trochim. Acta 1984, 29, 603–605.
50. T. Shono, S. Kashimura, Y. Yamaguchi et al., 72. A. J. Bellamy, G. Howat, I. S. Mackirdy, J.
Chem. Lett. 1987, 1511, 1512. Chem. Soc., Perkin Trans. 2 1978, 786–793.
51. T. Shono, S. Kashimura, Y. Yamaguchi et al., 73. G. C. Barret, J. Grattan, Tetrahedron Lett.
Tetrahedron Lett. 1987, 28, 4411–4414. 1979, 20, 4237–4240.
52. H. Maeda, T. Maki, H. Ohmori, Electrochem- 74. T. Shono, I. Nishiguchi, H. Ohmizu, Chem.
istry (Denki Kagakai) 1994, 62, 1109–1114. Lett. 1976, 1233–1236.
53. H. Maeda, T. Maki, H. Ohmori, Tetrahedron 75. T. Shono, I. Nishiguchi, H. Ohmizu et al., J.
Lett. 1992, 33, 1347–1350. Am. Chem. Soc. 1978, 100, 545–550.
54. H. Maeda, T. Maki, H. Ohmori, Chem. Lett. 76. E. Kariv-Miller, J. Mihachi, J. Org. Chem.
1995, 249–250. 1986, 51, 1041–1045.
55. H. Maeda, H. Ashie, T. Maki et al., Chem. 77. S. Kashimura, M. Ishifune, Y. Murai et al.,
Pharm. Bull. 1997, 45, 1729–1733. Tetrahedron Lett. 1995, 36, 5041–5044.
56. M. M. Baizer, J. P. Petrovich, Progress in 78. T. Shono, N. Kise, T. Suzumoto et al., J. Am.
Physical Organic Chemistry, Wiley-Inter- Chem. Soc. 1986, 108, 4676, 4677.
science, New York, 1970, Vol 7. 79. T. Shono, N. Kise, Tetrahedron Lett. 1990, 31,
57. S. Swann Jr., Technique of Organic Chemistry, 1303–1306.
Wiley-Interscience, New York, 1956, Vol. 2. 80. T. Shono, N. Kise, T. Fujimoto et al., J. Org.
58. H. Kita, S. Ishikura, A. Katayama, Elec- Chem. Soc. 1992, 57, 7175–7187.
trochim. Acta 1974, 19, 555–560. 81. T. Shono, S. Kashimura, Y. Mori et al., J.
59. J. Grimshaw in Organic Electrochemistry, Org. Chem. 1989, 54, 6001–6003.
(Eds.: H. Lund, O. Hammerich), 4th ed., 82. T. Shono, Y. Morishima, N. Moriyoshi et al.,
Marcel Dekker, New York, 2001, Chap. 10. J. Org. Chem. 1994, 59, 273–275.
60. S. Swann Jr., E. Onstott, F. Baastad, Trans. 83. S. Kashimura, M. Ishifune, Y. Murai et al.,
Electrochem. Soc. 1955, 102, 113–118. Tetrahedron Lett. 1996, 37, 6737–6740.
61. J. Armand, L. Boulares, Bull. Chim. Fr. 1975, 84. S. Kashimura, M. Ishifune, Y. Murai et al.,
711–718. Chem. Lett. 1996, 309, 310.
62. J. H. Stocker, R. M. Jenevein, Collect. Czech. 85. T. Shono, N. Kise, T. Fujimoto, Tetrahedron
Chem. Commun. 1971, 36, 925–927. Lett. 1991, 32, 525–528.
63. L. Horner, D. Degner, Electrochem. Acta 86. C. M. Lieber, N. S. Lewis, J. Am. Chem. Soc.
1974, 19, 611–620. 1984, 106, 5033, 5034.
64. W. J. M. van Tilborg, L. I. G. Dekker, C. J. 87. G. Calzaferri, K. Haedener, J. Li, J. Pho-
Smit, Recl. Trav. Chim. Pays-Bas 1978, 97, tochem. Photobiol., A 1992, 64, 259–262.
321–326. 88. S. Chardon-Nobalt, D. Alian, R. Ziessel et al.,
65. W. J. M. van Tilborg, C. J. Smit, R. A. von J. Electroanal. Chem. 1998, 444, 253–260.
Santen, Recl. Trav. Chim. Pays-Bas 1979, 98, 89. K. Bujno, R. Bilewich, L. Siegfried et al.,
526–531. Electrochim. Acta 1997, 42, 1201–1206.
217
8
Oxidation and Reduction of
Halogen-containing Compounds
Dennis G. Peters
Indiana University, Bloomington, Indiana
8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
8.2 Anodic Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219

8.2.1 Halogenated Alkanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
8.2.2 Alicyclic Halides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
8.2.3 Aryl Halides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
8.3 Cathodic Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221

8.3.1 Halogenated Alkanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
8.3.2 Halogenated Alkenes and Alkynes . . . . . . . . . . . . . . . . . . . . . . . 223
8.3.3 Benzyl Halides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
8.3.4 Alicyclic Halides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
8.3.5 Aryl Halides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
8.3.6 Acyl and Phenacyl Halides . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
8.3.7 Aliphatic α-Halocarbonyl Compounds . . . . . . . . . . . . . . . . . . . . . 227
8.3.8 Halogenated Heterocyclic Compounds . . . . . . . . . . . . . . . . . . . . 228
8.3.9 Catalytic Reduction of Carbon–Halogen Bonds . . . . . . . . . . . . . . 229
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
219
8.1 8.2.1
Introduction Halogenated Alkanes
Among many classes of organic com- At a platinum anode in acetonitrile, a

pounds, halogen-containing species is one primary alkyl iodide undergoes oxida-
of the most thoroughly investigated. This tion to give a carbocation that reacts
chapter offers a brief overview of both the with the solvent to give an intermediate
oxidation and reduction of halogenated or- (1), and the latter species is converted
ganic compounds. Limitations of space to an N -alkylacetamide (2) during an
preclude a comprehensive bibliography; ether–water workup [5]:
mainly, the most important and recent
publications are cited here. Where the RI R+ + e− + 1/2 I2
same author or authors have published
+
a series of papers on a subject, often only R+ + CH3CN RN C CH3
the most recent reference is given. Addi- (1)
tional information can be obtained from O
other more expansive treatments [1–3]. By
consulting references cited within the ar- 1 + H2O RNH C CH3
(2)
ticles listed at the end of this chapter, the
interested reader can gain an even more (1)
complete picture of this subject. where, among other groups, R=CH3 ,
C2 H5 , (CH3 )2 CH, C4 H9 , and (CH3 )3 -
CCH2 (Eq. 1). However, other evidence [6]
8.2 suggests that a cation radical (RI+• )
Anodic Processes is initially generated at the anode.
Polyfluoroalkyl iodides can be trans-
As revealed in the following three sections, formed anodically into amides, esters, and
work dealing with the electrochemical oxi- ethers [7]. Secondary alkyl iodides afford
dation of halogenated organic compounds N -alkylacetamides (2) upon oxidation at
is centered largely on the behavior of alkyl, platinum in acetonitrile [8], and various
alicyclic, and aryl halides. A review by mechanistic features of the oxidation of
Becker [4] provides an especially good per- both primary and secondary alkyl iodides
spective of developments in these areas. have been probed [9].
220 8 Oxidation and Reduction of Halogen-containing Compounds
Controlled-potential oxidations of a However, electrooxidation of 1-bromoada-

number of primary, secondary, and mantane involves the transfer of more
tertiary alkyl bromides at platinum than three electrons to afford N -(1-
electrodes in acetonitrile have been adamantyl)acetamide. In a comparable
investigated [10]. For compounds such study of the oxidation of 2-
as 2-bromopropane, 2-bromobutane, tert- haloadamantanes and their methyl-
butyl bromide, and neopentyl bromide, a substituted analogues [13], it was observed
single N -alkylacetamide is produced. On that the products depend upon the identity
the other hand, for 1-bromobutane, 1- of the halogen atom as well as the number
bromopentane, 1-bromohexane, 1-bromo- of bridgehead methyl groups.
3-methylbutane, and 3-bromohexane, a Oxidation of either cyclopropyl methyl
mixture of amides arises. It was proposed iodide or cyclobutyl iodide at plat-
that one electron is removed from inum in acetonitrile, followed by an
each molecule of starting material and aqueous workup, leads to a mixture
that the resulting cation radical (RBr+• ) of N -(cyclopropyl methyl)acetamide and
decomposes to yield a carbocation (R+ ). N -cyclobutylacetamide, presumably be-
Once formed, the carbocation can react cause the intermediate cyclopropylmethyl
(either directly or after rearrangement) cations can rearrange partially to a cy-
clobutyl cation; both react with ace-
with acetonitrile eventually to form an
tonitrile to form immonium cations
N -alkylacetamide, as described above for
that are hydrolyzed to the isomeric
alkyl iodides. In later work, Becker [11]
acetamides [14]. Cyclopentyl, cyclohexyl,
studied the oxidation of 1-bromoalkanes
and cycloheptyl bromides have been ox-
ranging from methyl to heptyl bromide.
idized to afford a mixture of the corre-
He observed that, as the carbon-chain
sponding N -cycloalkylacetamide and cy-
length is increased, the coulombic yield
cloalkene, whereas cyclobutyl bromide
of amides decreases as the number of
gives only N -cyclobutylacetamide, and
different amides increases.
bromocyclopropane is converted into
N -allylacetamide [15]. Polycyclic bridge-
8.2.2
head iodides undergo electrooxidation
Alicyclic Halides
at glassy carbon in acetonitrile to
form N -alkylacetamides [16]; for ex-
Koch and Miller [12] reported that oxida-
ample, N -(1-bicyclo[2.1.1]hexyl)acetamide
tion of 1-chloro- and 1-fluoroadamantane
was obtained in 55% yield from 1-
at a platinum anode in acetonitrile is a
iodobicyclo[2.1.1]hexane.
two-electron process leading to the for-
mation of the corresponding N -(3-halo-1-
8.2.3
adamantyl)acetamide in yields of 91 and
Aryl Halides
65%, respectively (Eq. 2):
In early work, the oxidation of iodoben-
X X
zene at platinum in acetonitrile was
O shown to give a cation radical (3),
which reacts with excess starting mate-
NH C CH3
rial to yield the 4-iododiphenyliodonium
(2) cation [5] (Scheme 1).
8.3 Cathodic Processes 221
+•
I I + e−
(3)
+
3 + I I I + e− + H +
Scheme 1 Anodic coupling of iodobenzene to the 4-iododiphenyliodonium cation [5].
Parker and Eberson [17] demon- 8.3.1

strated that the oxidation of 9,10- Halogenated Alkanes
dibromoanthracene in the presence of
a nucleophile (e.g. 3,5-lutidine) re- Depending on the electrode material, the
sults in the replacement of a bromine potential, the solvent, and the supporting
by the nucleophile. In a series of electrolyte, the reduction of an alkyl
papers [18], various polyfluoroaromatic monohalide (RX) at an inert cathode can
amines were oxidized at platinum in lead to a radical (R• ) or a carbanion (R− )
an acetone–water mixture; for exam- intermediate, as shown in the following
ple, octafluoroacridone was synthesized mechanistic Scheme 3.
from 2-aminononafluorobenzophenone Once formed, the radical intermediate
(Scheme 2). (R• ) can couple to afford a dimer (R2 ), can
In a potassium acetate–acetic acid disproportionate to give an alkane (RH)
medium, 2-fluoro- and 4-fluoroanisole and an olefin (R(−H)), or can accept a
can be oxidized at platinum to af- hydrogen atom from a donor (such as the
ford 2-acetoxy- and 4-acetoxyanisole, re- solvent, SH) to give an alkane. A carbanion
spectively [19]. Using a platinum anode (R− ) can be protonated by the solvent (or
in a trifluoroacetic acid–potassium tri- a deliberately added acid, HB) to yield an
fluoroacetate solution, Blum and Ny- alkane. In addition, RX can undergo E2
berg [20] electrooxidized hexafluoroben- and SN 2 reactions with B− , and R− can
zene to tetrafluorobenzoquinone in 75% attack RX to form a dimer.
yield, and octafluoronaphthalene was con- Tertiary alkyl halides are easier to reduce
verted into hexafluoronaphthoquinone in than secondary alkyl halides, which are
60% yield. easier to reduce than primary alkyl halides.
Carbon–iodine bonds are easier to reduce
than carbon–bromine bonds, which are
8.3 easier to reduce than carbon–chlorine
Cathodic Processes bonds [1–3].
Primary [21] and secondary [22] alkyl io-
In this part of the chapter, the discussion is dides are reduced in a stepwise fashion
focused on the direct cathodic reduction of at mercury cathodes to form alkyl radicals
halogenated organic compounds, although and alkyl carbanions; the alkyl radicals un-
the last section will address the increas- dergo coupling and disproportionation as
ingly active area of catalytic reductions of well as interaction with the electrode to
carbon–halogen bonds. yield diorganomercury compounds, and
F H2N F O F
F O F
F F
F F
F NH F
F F
F F F F
Scheme 2 Octafluoroacridone by way of anodic nuclear substitution [18].
Fast
RX + e− [RX− •] R• + X−
R• + e− R−
Combination
R2
2R • Disproportionation
RH + R(−H)
R • + SH RH + S •
R− + SH (or HB) RH + S− (or B−)
Scheme 3 Mechanism of cathodic cleavage of halogenated alkanes.
the alkyl carbanions afford mainly alkanes reductive coupling of 1,1,1-trichloro-2,2,2-

and olefins. However, the reduction of trifluoroethane with aldehydes [26] and of
primary and secondary alkyl bromides at gem-polyhalo compounds with activated
mercury gives alkyl carbanions only [21, olefins [27] is possible. Several studies
22], whereas tert-butyl bromide exhibits a have involved the electrogeneration
stepwise reduction [23]. An investigation of the trichloromethyl anion, which
of the reduction of primary, secondary, reacts with a number of substrates [28].
and tertiary alkyl iodides and bromides Vicinal dihalides, such as 1,2-dibromo-1,2-
at glassy carbon has revealed the for- diphenylethane, undergo a two-electron
mation of alkanes, olefins, and coupling reduction with loss of two halides to yield
products [24]. an olefin [29]. Electrochemical reduction
Electrochemical reduction of a variety of α,ω-dihaloalkanes at both mercury
of polyhalogenated alkanes has been and carbon cathodes has been extensively
undertaken. Stepwise dechlorination of investigated [30, 31]; from starting
gem-dichloro- and gem-trichloroalkanes materials with short carbon chains,
occurs. Dichloromethane can be reduced for example, 1,3-dibromopropane and
in the presence of an olefin 1,4-dibromobutane, the corresponding
to form a cyclopropane [25], and cycloalkane can be prepared. Reduction
C6H5 H C6H5 C6H5

Ni cathode
Br(CH2)3Br + C C
H C6H5
Scheme 4 Cathodic alkylation of trans-stilbene [32].

of 1,3-dibromopropane at a nickel cathode benzyl chloride in the presence of ke-

in the presence of an arylalkene affords the tones and aldehydes [28]. Steric effects on
cyclopentane adduct (Scheme 4) [32]. the reductive coupling of α-substituted
benzyl bromides have been probed [41].
8.3.2 Reduction of trichloromethylbenzene in
Halogenated Alkenes and Alkynes the presence of acetic anhydride gives
2-acetoxy-1-chloro-1-phenyl-1-propene and
Vinyl halides, such as cis- and trans-3- 1,2-diacetoxy-1-phenyl-1-propene [42], and
iodo-3-hexene [33], undergo a one-electron cathodic addition of trichloromethylben-
reduction with expulsion of a halide ion zene to ketones yields α,β-unsaturated
to give a vinyl radical that is further ketones [43]. Amino acids can be obtained
reduced and protonated. When vinyl via the coupling of Schiff bases with elec-
halides are electrolyzed in the presence trogenerated benzyl carbanions [44].
of trimethylchlorosilane, silylated products
are obtained [34]. 8.3.4
A classic paper by Baizer and Chruma Alicyclic Halides
[35] describes synthetic applications based
on the reduction of allyl halides. Electrol- Mann and Barnes [45] have discussed
yses of 4-bromo- and 4-chloro-2-butene the mechanism of reduction of sub-
can be employed for the allylation of stituted and optically active 1-bromo-
acetone and benzaldehyde [36], and the re- and 1-iodocyclopropanes, and Hazard and
coworkers [46] have investigated the reduc-
duction of allyl halides in the presence
tion of 1-bromo-1-carboxy-2,2-diphenyl-
of trimethylchlorosilane affords silylated
cyclopropane. At mercury cathodes, elec-
compounds [34].
trolyses of 1-bromo- and 1-iodonorbornane
Several publications deal with acetylenic
proceed via two-electron cleavage of the
halides that can undergo reductive in-
carbon–halogen bond to give mainly nor-
tramolecular cyclization [37]. For example,
bornane, plus a small amount of bis(1-
electrolysis of 6-iodo-1-phenyl-1-hexyne at
norbornyl)mercury [47].
a carbon cathode gives benzylidenecy-
Electrochemical reduction of 2,2-
clopentane in 36% yield. dichloronorbornane, 2-exo-bromo-2-endo-
chloronorbornane, and 2-endo-bromo-2-
8.3.3 exo-chloronorbornane gives mixtures of
Benzyl Halides nortricyclene and endo-2-chloronorbor-
nane [48]. Electrolysis of 1-bromo-
Mechanistic aspects of the reduction of 3-chlorocyclobutane at mercury yields
benzyl halides at mercury have been ex- bicyclo[1.1.0]butane, cyclobutane, and
tensively investigated [35, 38]. From the cyclobutene [49]. Hoffmann and Voss [50]
reduction of benzyl iodide at platinum, observed that 1,3-dibromocycloalkanes
Koch and coworkers [39] obtained toluene, can undergo ring-closure at a platinum
bibenzyl, and hydrocinnamonitrile. Elec- cathode (Eq. 3):
trolysis of benzyl chloride in the presence
of acyl chlorides can be used to synthe- Br Br
+
size alkyl benzyl ketones [40], whereas
alcohols are formed by electrolysis of (3)
Reduction of 1-bromo-4-chlorobicyclo- Savéant and coworkers [58] have played a

[2.2.0]hexane affords 1,4 -bicyclo[2.2.0]- central role in characterizing the behavior
hexane [51]. Wiberg and coworkers [52] of aryl halides.
electrolyzed 1,4-dibromobicyclo[2.2.2]oct- Iodobenzene and bromobenzene [59], as
ane and obtained evidence that well as p-iodoanisole [60], can be elec-
[2.2.2]propellane is a transient in- trolyzed at mercury cathodes in the pres-
termediate, and electrolysis of 1,5- ence of carbon dioxide to give carboxylic
dibromobicyclo[3.2.1]octane leads to acids. Reduction of various aryl halides in
[3.2.1]propellane [49]. Studies of the the presence of trimethylchlorosilane af-
reductions of 1,3-dihaloadamantanes, fords silylated products [61]. Kariv-Miller
1,4-dihalobicyclo[2.2.2]octanes, and 1,3- and Vajtner [62] converted fluorobenzene
dihalobicyclo[1.1.1]pentanes have been re- to benzene by carrying out electrolyses
ported [53]. When 1,4-dihalonorbornanes at mercury cathodes in diglyme con-
are electrolyzed at mercury, norbor- taining the dimethylpyrrolidinium cation
nane and bis(1-norbornyl)mercury are (DMP+ ); the latter behaves catalytically
produced, along with small quanti- by being reduced to an amalgam that re-
ties of 1,1 -binorbornyl, and [2.2.1]pro- acts with fluorobenzene to form the anion
pellane is an intermediate [54]. Selec- radical (C6 H5 F−• ), which undergoes a car-
tive electrochemical trimethylsilylation bon–fluorine bond scission, followed by
reduction and protonation to yield ben-
of tetrachlorocyclopropane to afford 1-
zene. Reduction of an aryl halide gives an
(trimethylsilyl)trichlorocyclopropane has
aryl carbanion, which, by deprotonating
been described [55]. Chlordane, aldrin, and
an appropriate nitrile, can lead to coupling
alodan (chlorinated insecticides) can be
of the nitrile with esters, aldehydes, and
electrochemically dechlorinated [56], and
ketones [63].
lindane (γ -hexachlorocyclohexane) can
Dihalobenzenes, such as p-bromoiodo-
undergo stepwise dechlorination [57].
benzene, can be reduced in a step-
wise manner [64]. An investigation of
8.3.5 the electrochemistry of the entire fam-
Aryl Halides
ily of chlorinated benzenes has been
reported [65], and the dechlorinations of
Earlier, in Sect. 8.3.1, a generalized mech- 1,2,3,5-tetrachlorobenzene [57] and of 2,4-
anistic scheme for the reduction of simple dichlorophenoxyacetic acid (a herbicide)
alkyl halides was presented. What dis- have been accomplished [66]. Several pa-
tinguishes aryl halides (ArX) from alkyl pers dealing with the reduction of chlori-
halides (RX) is the finite lifetime of nated biphenyls have appeared [67–69].
the initially electrogenerated anion radi-
cal (ArX−• ). Thus, although ArX exhibits 8.3.6
the same kinds of reactions as RX, a key Acyl and Phenacyl Halides
difference is that the transient anion rad-
ical (ArX−• ) can undergo a homogeneous Reduction of benzoyl chloride at mercury
electron-transfer reaction with the aryl rad- yields an acyl radical that dimerizes to form
ical (Ar• ) (Eq. 4): benzil. As quickly as it forms, benzil ac-
cepts an electron to form an anion radical
ArX−• + Ar•
−−
−−−
−ArX + Ar
−
(4) that is acylated by a molecule of benzoyl
O O
C6H5CH CH C Cl + e− C6H5CH CH C• + Cl−

(a)
C6H5CH2 O
2 C6H5CH2CH C O
(b) O CH2C6H5
Scheme 5 Cathodic reduction of cinnamoyl chloride to the corresponding ketene dimer [70b].
chloride; most probably, the resulting in- the carboxylic acid) is obtained as a by-
termediate is reduced again and acylated product of hydrolysis involving adventi-
one more time to afford a mixture of tious water.
cis- and trans-stilbenediol dibenzoate [70, Phenylacetyl chloride and hydrocin-
71]. An analogous set of reactions can namoyl chloride are reduced at mercury
be proposed for the reduction of both to form both acyl radicals and acyl anions
1-naphthoyl chloride and 2-naphthoyl chlo- as intermediates [76]. From electrolyses of
ride [70]. Cinnamoyl chloride undergoes a phenylacetyl chloride, the products include
one-electron reduction at mercury to give 1,4-diphenyl-2-butene-2,3-diol diphenylac-
a radical (Scheme 5a). This radical gains a etate, phenylacetaldehyde, toluene, 1,3-
hydrogen atom from the medium to form diphenylacetone, and 1,4-diphenyl-2,3-
a ketene, which immediately undergoes butanediol, and analogous species arise
dimerization (Scheme 5b). from the reduction of hydrocinnamoyl
In addition to studying the behavior of chloride. Reduction of phthaloyl dichlo-
benzoyl chloride, Cheek and Horine [72]
ride is a more complicated system [77]; the
have examined the reduction of benzoyl
electrolysis products are phthalide, biph-
fluoride; electrolysis of the latter com-
thalyl, and 3-chlorophthalide, but the latter
pound affords benzyl benzoate, diphenyl-
compound undergoes further reduction to
acetylene, stilbenol benzoate, and some
give phthalide, biphthalyl, and dihydrobi-
polymers. Another feature of the reduc-
phthalide.
tion of benzoyl chloride is the possibility
that both acyl radicals and acyl anions are Electrolysis of 2-furoyl chloride
involved as intermediates [71]. at mercury affords mainly 1,2-di(2-
Glutaryl dichloride undergoes reduction furyl)ethene-1,2-diol di(2-furoate); how-
at mercury to give 5-chlorovalerolactone ever, an interesting pair of minor
and valerolactone; a polymeric solid, pos- products are 1,2-di(2-furyl)-2-hydroxy-3-
sibly X[(CH2 )3 CHCl−O−C=O]n (CH2 )3 X cyanopropanone and 3-(2-furyl)acryloni-
(where X = CHO or CO2 H), is additionally trile, in which a fragment of the sol-
produced [73]. Heptanoyl chloride [71], vent (acetonitrile) is incorporated [78].
trimethylacetyl chloride [74], and cyclo- When 2,4,6-trimethylbenzoyl chloride
hexanecarbonyl chloride [75] can be re- is reduced at carbon or mercury
duced at carbon or mercury cathodes cathodes in acetonitrile, the major
to form the corresponding aldehydes; in products are 2,4,6-trimethylbenzaldehyde
addition, the anhydride (and sometimes and 3-(2,4,6-trimethylphenyl)acrylonitrile,
along with traces of 3-(2,4,6-trimethyl- products were formed – S-methylidene

phenyl)glutaronitrile and 3-(2,4,6-trimeth- bis(diphenylthioacetate), S-chloromethyl
ylphenyl)propionitrile [79]. diphenylthioacetate, and S-methyl di-
Reduction of 1-adamantanecarbonyl phenylthioacetate.
chloride at carbon or mercury leads Barba and coworkers [84–91] have pub-
to the quantitative formation of 1- lished a number of papers dealing with
adamantanecarboxaldehyde [80]. Muba- novel syntheses based on the reduc-
rak [81] investigated the reduction of tion of phenacyl bromides. Electrolysis
2-thiophenecarbonyl chloride at both of phenacyl bromide at a mercury cath-
carbon and mercury; the starting material ode leads to an intermediate, which
appears to undergo a two-electron reacts to give 2,4-diphenylfuran [84]. How-
reduction to form an acyl anion, which ever, when a proton donor (CH3 OH) is
leads to 1,2-di(2-thienyl)ethene-1,2-diol present, the reduction of phenacyl bro-
di(2-thiophenecarboxylate) as the major mide yields acetophenone and 2-bromo-
product and to 2-thiophenecarboxaldehyde 1,3-diphenyl-3,4-epoxy-butan-1-one. Inter-
as the minor product. estingly, if phenacyl bromide is slowly
Lozano and Barba [82] electrolyzed 2- introduced into an electrolysis cell so that
chloro-2-phenylacetyl chloride at mercury the unreduced starting material is main-
in methylene chloride and obtained tained at a low concentration, the products
derivatives of pyran-2-one and pyran-4- are different [85] (Scheme 7).
one, where R is H and C6 H5 CH2 CO, It is also possible to protect the carbonyl
respectively, at high and low current moiety of a phenacyl bromide via the re-
density (Scheme 6). In later work [83], action with semicarbazide hydrochloride;
the same workers reduced 2-bromo- then the semicarbazone can be electrolyt-
2,2-diphenylacetyl bromide in methylene ically dimerized, ultimately to afford a
dichloride saturated with hydrogen 2,5-diarylfuran [86]. Alternatively, the elec-
sulfide gas; three sulfur-containing trolytically formed dimer can be converted
OR O
C6H5 O
C6H5 C6H5 C6H5 C6H5
CH C +
O O O OR
Cl Cl
C6H5 C6H5
Scheme 6 Cathodic reduction of 2-chloro-2-phenylacetyl chloride to pyran-2-one and pyran-4-one
derivatives [82].
C6H5 O
O C C6H5
C6H5 C CH2Br C6H5 C6H5 +

C C C6H5 O
O
O O
Scheme 7 Cathodic reduction of phenacylbromide to trimer and dimer [85].

(via refluxing in dimethylformamide) to buffer gives a mixture of dicyclopropyl

a 3,6-diphenylpyridazine [87]. Reduction ketone and α-bromocyclopropyl cyclo-
of α-bromopropiophenone at mercury propyl ketone, whereas only the lat-
gives 1,4-diphenyl-2,3-dimethylbutan-1,4- ter product is obtained for the same
dione [88], and the reduction of phenacyl buffer in dimethylformamide [97]. Low-
bromides provides a synthetic path- temperature reduction of alkylated α,α -
way to 4-aryl-2-methylfurans [89] and dihaloketones to cyclopropanones (iso-
enol carbonates [90]. Finally, 3,7-diaryl- lated as hemiacetals or hemiacylals) can
2H-imidazo[2,1-b] [1, 3, 4]oxadiazines can be performed with highly alkylated start-
be prepared via reduction of the semicar- ing compounds [98]. Electrolysis of α,α -
bazones of phenacyl bromide [91]. dichloroketones at mercury in the pres-
ence of carboxylic acids, phenols, and
8.3.7 diethyl malonate leads to the forma-
Aliphatic α-Halocarbonyl Compounds tion of Favorskii-rearrangement products,
dechlorinated ketones, and addition prod-
Studies of aliphatic α-haloaldehydes in ucts [99]. In the presence of amines or phe-
water–dioxane have shown that the elec- nols, 1,1,3-tribromo- or 1,1,3-trichloro-3-
trochemical behavior of these compounds methyl-2-pentanone can be reduced to the
is affected by the equilibrium between corresponding α,β-unsaturated amides or
the hydrated and unhydrated forms of the
esters [100].
aldehyde [92]. Each carbon–halogen bond
In aqueous media, α-halocarboxylic
is broken in a two-electron, one-proton
acids and their esters undergo two-
process, and the resulting nonhalogenated
electron, one-proton reductive cleav-
aldehyde undergoes reduction at a more
age [101]. Electrolysis of ethyl bromoac-
negative potential [93].
etate at mercury affords mainly ethyl
Reduction of 2-bromo-3-pentanone at
acetate and diethyl succinate, along
mercury affords a mixture of 3-pentanone
with small amounts of diethyl fu-
and 1-hydroxy-3-pentanone, whereas elec-
trolysis of α,α -dibromoacetone in the marate, 1,2,3-tricarbethoxycyclopropane,
presence of benzoate gives a mixture and 1,2,3-tricarbethoxypropane [35]. Elec-
of products arising from both a car- trolysis of a solution containing α-chloro-
bon–bromine bond cleavage and an N -benzylacetamide, carbon dioxide, and
SN 2 displacement of bromide by ben- a probase (e.g. tetraethyl ethylenetetracar-
zoate [94]. In an acetic acid–acetate buffer, boxylate) has been used to synthesize N -
branched dibromo ketones, such as 2,4- benzyloxazolidine-2,4-dione (a biologically
dibromo-2,4-dimethyl-3-pentanone, are reactive compound) [102]. Maran [103] has
duced to α-acetoxy ketones; however, less examined the reduction of α-haloamides
highly substituted compounds, such as at mercury; for example, electrolysis
4,6-dibromo-5-nonanone, undergo sim- of (S)-(–)-2-bromo-N -phenylpropanamide
ple cleavage of both carbon–bromine yields propananilide, 2-(dimethylamino)-
bonds [95]. Other work dealing with the re- 5-methyl-3-phenyloxazolidin-4-one, and
duction of α,α -dibromoketones has been cis-1,4-diphenyl-3,6-dimethyl-2,5-dioxopip-
described [96]. erazine. Casadei and coworkers [104]
Reduction of bis(α-bromocyclopropyl) investigated the following process
ketone in an aqueous acetic acid–acetate (Scheme 8).
O O Cl
2e−
H3C C NH CH CCl3 H3C C NH CH C
OCOCH3 Cl
Scheme 8 Cathodic β-elimination from β-haloacetate [104].
Reductions of ethyl α,β-dibromopro- cathode affords 3,4,6-trichloro-2-picolinic

panoate, ethyl α,γ -dibromobutyrate, and acid, which can be further reduced to 3,6-
methyl α,δ-dibromovalerate at mercury dichloro-2-picolinic acid [118, 119].
have been characterized [105]. Studies of the behavior of hetero-
cyclic compounds possessing two nitrogen
8.3.8 atoms are rare. There is a survey of the
Halogenated Heterocyclic Compounds reduction of 6-haloquinoxalines and 2-
halophenazines [116], and a report about
Halogenated heterocyclic compounds ex- the reduction of 4-chloroquinazoline [120].
hibit a behavior similar to that of aryl Halogenated thiazoles are reduced at
halides. Accordingly, at mercury in aque- mercury in a process involving two elec-
ous media, monohalogenated pyridines, trons and a proton to give thiazole [121]. By
in either their unprotonated or pro- electrolyzing 2-bromothiazole in an acidic
tonated forms, undergo a two-electron water–ethanol mixture, Iversen [122] ob-
cleavage of the carbon–halogen bond, tained thiazole in 88% yield. Reduction of
followed by protonation to yield pyri- 2-bromothiazole at carbon involves both
dine [106]. Redox catalysis has been
radical and carbanion intermediates, and
used to probe the reduction of 2-
thiazole is formed quantitatively [123].
bromo-, 3-bromo-, 2-chloro-, and 3-
For the reduction of bromo- and iodothi-
chloropyridine at mercury [58]. Reduction
ophenes in both aqueous and nonaqueous
of 2,5-dibromo-, 2,3-dichloro-, and 2,6-
media, cleavage of each carbon–halogen
dichloropyridine in ethanol–water has
bond is a two-electron, one-proton pro-
been studied polarographically [107], and
cess [124]. Pletcher and Razaq [125] pre-
the electrochemical behavior of mono-
and dihalopyridines at carbon cath- pared 3-bromothiophene by electrolyzing
odes has been characterized [108]. Cham- 2,3,5-tribromothiophene, and Gedye and
bers and coworkers [109] have stud- coworkers [126] investigated the reduction
ied the reduction of some polyhalopy- of tetrabromo-, tetraiodo-, 2,3,4-tribromo-,
ridines at mercury. There is a patent and 3,4-dibromothiophene at various cath-
describing the electrosynthesis of 2,3,5- odes. Procedures for the electrosyn-
trichloropyridine from pentachloropyri- thesis of brominated thiophenes have
dine [110, 111], and two patents deal with been reported [127]. Reduction of sev-
the reduction of pentachloropyridine to eral dihalothiophenes at carbon gives
2,3,5,6-tetrachloropyridine [112–115]. rise to an electrolytically induced halo-
Two papers concerning the reduction gen dance [128] and, by reducing
of chlorinated quinolines have been pub- a substituted 3-chlorobenzo[b]thiophene,
lished [116, 117]. Electrolysis of 3,4,5,6- Justice and Hall [129, 130] obtained
tetrachloro-2-picolinic acid at a silver 3-hydrobenzo[b]thiophene.
8.3.9 vinyl bromides, 2-bromoindene, and 7,7-

Catalytic Reduction of Carbon–Halogen dichlorobicyclo[4.1.0]heptane [139], and
Bonds with bornyl, isobornyl, and exo- and endo-
norbornyl bromides [140].
Although an up-to-date review [3] of this Two reviews provide important infor-
subject has recently appeared, a summary mation about the use of transition-metal
is presented here. In many instances, complexes as mediators [141] and about
a carbon–halogen bond can be cleaved catalytic processes involving a wider vari-
chemically with an electron-transfer medi- ety of metal species [142].
ator (catalyst) that is electrogenerated at Catalytic processes based on the use
potentials more positive than those re- of electrogenerated nickel(0) bipyridine
quired for the direct reduction of the complexes have been a prominent theme
carbon–halogen bond. Electrogenerated in the laboratories of Nédélec, Périchon,
anion radicals of aromatic hydrocarbons and Troupel; some of the more re-
were the first mediators to be used, cent work has involved the follow-
but in recent years electrogenerated lowing: (1) cross-coupling of aryl halides
valent transition-metal complexes and with ethyl chloroacetate [143], with ac-
other organometallic species have enjoyed tivated olefins [144], and with activated
increasing popularity as catalysts. alkyl halides [145], (2) coupling of or-
Lund and coworkers [131] pioneered ganic halides with carbon monoxide to
the use of aromatic anion radicals as form ketones [146], (3) coupling of α-
mediators in a study of the catalytic chloroketones with aryl halides to give
reduction of bromobenzene by the α-arylated ketones [147], and (4) formation
of ketones via reduction of a mixture of a
electrogenerated anion radical of chrysene.
benzyl or alkyl halide with a metal car-
Other early investigations involved the
bonyl [148].
catalytic reduction of 1-bromo- and 1-
Nickel(0) triphenylphosphine can be
chlorobutane by the anion radicals of
used to couple aryl halides and alkenes
trans-stilbene and anthracene [132], of 1-
to synthesize substituted olefins [149], 1,2-
chlorohexane and 6-chloro-1-hexene by the
bis[(di-2-propylphosphino)benzene]nick-
naphthalene anion radical [133], and of 1-
el(0) can be used to couple aryl
chlorooctane by the phenanthrene anion halides [150], and 1,2-bis[(diphenylphos-
radical [134]. Simonet and coworkers [135] phino)ethane]nickel(0) can be used to
pointed out that a catalytically formed prepare benzoic acid from bromoben-
alkyl radical can react with an aromatic zene in the presence of carbon
anion radical to form an alkylated aromatic dioxide [151].
hydrocarbon. Additional, comparatively Electrogenerated nickel(I) salen has
recent work has centered on electron been employed catalytically for the re-
transfer between aromatic anion radicals duction of benzal chloride [152] and
and 1,2-dichloro-1,2-diphenylethane [136], for the reductive coupling of 2-
on reductive coupling of tert-butyl bromo- and 2-iodoethanol to pre-
bromide with azobenzene, quinoxaline, pare 1,4-butanediol [153]. Electrogener-
and anthracene [137], and on the ated nickel(I) cyclams have been used
reactions of aromatic anion radicals with as catalysts for the reductive in-
substituted benzyl chlorides [138], with tramolecular cyclizations of o-haloaryl
compounds possessing unsaturated side References

chains [154], of 2-bromoalkyl- and 3-
bromoalkyl-2-cyclohexen-1-ones [155], of 1. M. D. Hawley in Encyclopedia of Electro-
chemistry of the Elements (Eds.: A. J. Bard,
o-bromoacryloylanilides to give five-
H. Lund), Marcel Dekker, New York, 1980,
membered lactams [156], of acetylenic pp. 1–308, Vol. XIV.
halides to prepare functionalized (meth- 2. J. Casanova, V. P. Reddy in The Chemistry
ylene)cyclopentanes [157], and of 2-bromo- of Functional Groups, Supplement D2 (Eds.:
and 2-iodoethanol to afford ethylene ox- S. Patai, Z. Rappoport), Wiley, New York,
1995, pp. 1003–1067.
ide [158]. 3. D. G. Peters in Organic Electrochemistry
Cobalt(I) salen has been employed (Eds.: H. Lund, O. Hammerich), 4th ed.,
as a catalyst for the reduction of the Marcel Dekker, New York, 2000, pp.
following species: benzal chloride [159]; 341–378.
benzotrichloride [160]; 1-bromobutane, 1- 4. J. Y. Becker in The Chemistry of Func-
tional Groups, Supplement D (Eds.: S. Patai,
iodobutane, and 1,2-dibromobutane [161]; Z. Rappoport), Wiley, New York, 1983,
iodoethane [162], benzyl chloride [163], pp. 203–286.
and ethyl chloroacetate [164]. Rusling and 5. L. L. Miller, A. K. Hoffmann, J. Am. Chem.
coworkers have investigated the use Soc. 1967, 89, 593–597.
6. A. Laurent, R. Tardivel, C. R. Acad. Sci., Ser.
of cobalt(I) salen, as well as vitamin
C 1971, 272, 8–10.
B12s and cobalt(I) phthalocyanine, in 7. J. Y. Becker, B. E. Smart, T. Fukunaga, J.
both homogeneous phase and bicontin- Org. Chem. 1988, 53, 5714–5720.
uous microemulsions for the catalytic 8. A. Laurent, E. Laurent, R. Tardivel, Tetrahe-
reduction of vicinal dibromides [165] and dron 1974, 30, 3423–3429.
9. L. L. Miller, B. F. Watkins, Tetrahedron Lett.
1-bromobutane, 1-bromododecane, and 1974, 4495–4498.
trans-1,2-dibromocyclohexane [166]. 10. J. Y. Becker, J. Org. Chem. 1977, 42,
Electrogenerated samarium(II) catalyzes 3997–4000.
the reduction of organic halides [167] 11. J. Y. Becker, Tetrahedron Lett. 1978,
and the reductive coupling of 3- 1331–1334.
12. V. R. Koch, L. L. Miller, J. Am. Chem. Soc.
chloropropanoate or of allyl chloride 1973, 95, 8631–8637.
with ketones [168, 169]. Reactions of 13. F. Vincent, R. Tardivel, P. Mison, Tetrahe-
iron(II) porphyrin with vicinal dihalides dron 1976, 32, 1681–1688.
and various organic monohalides have 14. E. Laurent, R. Tardivel, Tetrahedron Lett.
1976, 2779–2782.
been examined [170], and iron(II)
15. J. Y. Becker, D. Zemach, J. Chem. Soc.,
myoglobin immobilized in biomembrane- Perkin Trans. 2 1979, 914–917.
like surfactant films on graphite 16. R. S. Abeywickrema, E. W. Della, S. Flet-
electrodes catalytically dehalogenates cher, Electrochim. Acta 1982, 27, 343–346.
ethylene dibromide and trichloroacetic 17. V. D. Parker, L. Eberson, J. Chem. Soc.,
Chem. Commun. 1969, 973–974.
acid [171]. Yoshida and coworkers reduced
18. C. M. Jenkins, A. E. Pedler, J. C. Tatlow,
mixtures of organic halides and iron Tetrahedron 1971, 27, 2557–2560.
pentacarbonyl, followed by addition of 19. K. Nyberg, L.-G. Wistrand, J. Chem. Soc.,
an electrophile, to prepare carbonyl Chem. Commun. 1976, 898–899.
compounds [172] and, in related work, 20. Z. Blum, K. Nyberg, Acta Chem. Scand.
1979, B33, 73–75.
iron pentacarbonyl served as a catalyst 21. D. M. La Perriere, W. F. Carroll Jr., B. C.
for the conversion of alkyl halides into Willett et al., J. Am. Chem. Soc. 1979, 101,
aldehydes [173, 174]. 7561–7568.
22. M. S. Mubarak, D. G. Peters, J. Org. Chem. 47. W. F. Carroll Jr., D. G. Peters, J. Org. Chem.
1982, 47, 3397–3403. 1978, 43, 4633–4637.
23. K. L. Vieira, D. G. Peters, J. Org. Chem. 48. A. J. Fry, R. G. Reed, J. Am. Chem. Soc.
1986, 51, 1231–1239. 1972, 94, 8475–8484.
24. J. A. Cleary, M. S. Mubarak, K. L. Vieira 49. M. R. Rifi, Collect. Czech. Chem. Commun.
et al., J. Electroanal. Chem. 1986, 198, 1971, 36, 932–935.
107–124. 50. J. Hoffmann, J. Voss, Chem. Ber. 1992, 125,
25. S. Durandetti, S. Sibille, J. Périchon, J. Org. 1415–1419.
Chem. 1991, 56, 3255–3258. 51. J. Casanova, H. R. Rogers, J. Org. Chem.
26. T. Shono, N. Kise, H. Oka, Tetrahedron Lett. 1974, 39, 3803.
1991, 32, 6567–6570. 52. K. B. Wiberg, G. A. Epling, M. Jason, J. Am.
27. E. Léonel, J. P. Paugam, S. Condon- Chem. Soc. 1974, 96, 912–913.
Gueugnot et al., Tetrahedron 1998, 54, 53. W. Adcock, C. I. Clark, A. Houmam et al., J.
3207–3218. Am. Chem. Soc. 1994, 116,
28. S. Sibille, E. d’Incan, L. Leport et al., 4653–4659.
Tetrahedron Lett. 1986, 27, 3129–3132. 54. W. F. Carroll Jr., D. G. Peters, J. Am. Chem.
29. T. Lund, C. Bjørn, H. S. Hansen et al., Acta Soc. 1980, 102, 4127–4134.
Chem. Scand. 1993, 47, 877–884. 55. G. K. Surya Prakash, H. A. Buchholz,
30. J. C. Bart, D. G. Peters, J. Electroanal. Chem. D. Deffieux et al., Synlett 1994, 819–820.
1990, 280, 129–144. 56. J. Gassman, J. Voss, G. Adiwidjaja, Z.
31. W. A. Pritts, D. G. Peters, J. Electroanal. Naturforsch., B 1995, 50, 953–958.
Chem. 1995, 380, 147–160. 57. S. M. Kulikov, V. P. Plekhanov, A. I.
32. E. Léonel, J. P. Paugam, J.-Y. Nédélec et al., Tsyganok et al., Electrochim. Acta 1996, 41,
527–531.
J. Chem. Res.(S) 1995, 278–279.
58. C. P. Andrieux, C. Blocman, J. M. Dumas-
33. A. J. Fry, M. A. Mitnick, J. Am. Chem. Soc.
Bouchiat et al., J. Am. Chem. Soc. 1979, 101,
1969, 91, 6207–6208.
3431–3441.
34. J. Yoshida, K. Muraki, H. Funahashi et al.,
59. T. Matsue, S. Kitahara, T. Osa, Denki Ka-
J. Org. Chem. 1986, 51, 3996–4000.
gaku 1982, 50, 732–735.
35. M. M. Baizer, J. L. Chruma, J. Org. Chem.
60. N. S. Murcia, D. G. Peters, J. Electroanal.
1972, 37, 1951–1960.
Chem. 1992, 326, 69–79.
36. M. Tokuda, S. Satoh, H. Suginome, J. Org. 61. M. Bordeau, C. Biran, P. Pons et al., J. Org.
Chem. 1989, 54, 5608–5613. Chem. 1992, 57, 4705–4711.
37. M. S. Mubarak, D. D. Nguyen, D. G. Peters, 62. E. Kariv-Miller, Z. Vajtner, J. Org. Chem.
J. Org. Chem. 1990, 55, 2648–2652. 1985, 50, 1394–1399.
38. O. R. Brown, H. R. Thirsk, B. Thornton, 63. R. Barhdadi, J. Gal, M. Heintz et al., Tetra-
Electrochim. Acta 1971, 16, 495–503. hedron 1993, 49, 5091–5098.
39. D. A. Koch, B. J. Henne, D. E. Bartak, J. 64. A. J. Fry, M. A. Mitnick, R. G. Reed, J. Org.
Electrochem. Soc. 1987, 134, 3062–3067. Chem. 1970, 35, 1232–1234.
40. T. Shono, I. Nishiguchi, H. Ohmizu, Chem. 65. D. Petersen, M. Lemmrich, M. Altrogge
Lett. 1977, 1021–1024. et al., Z. Naturforsch., B 1990, 45,
41. A. J. Fry, J. M. Porter, P. F. Fry, J. Org. 1105–1107.
Chem. 1996, 61, 3191–3194. 66. A. I. Tsyganok, K. Otsuka, Electrochim. Acta
42. J.-P. Gisselbrecht, H. Lund, Acta Chem. 1998, 43, 2589–2596.
Scand. 1985, B39, 823–827. 67. S. O. Farwell, F. A. Beland, R. D. Geer, J.
43. M. Steiniger, H. J. Schäfer, Angew. Chem. Electroanal. Chem. 1975, 61, 315–324.
1982, 94, 75–76. 68. M. Maruyama, K. Murakami, Nippon Ka-
44. T. Iwasaki, K. Harada, J. Chem. Soc., Perkin gaku Kaishi 1976, 536–539.
Trans. 1 1977, 1730–1733. 69. J. F. Rusling, J. V. Arena, J. Electroanal.
45. C. K. Mann, K. K. Barnes, Electrochemical Chem. 1985, 186, 225–235.
Reactions in Nonaqueous Systems, Marcel 70. (a) A. Guirado, F. Barba, C. Manzanera
Dekker, New York, 1970, pp. 206–211. et al., J. Org. Chem. 1982, 47, 142–144.
46. R. Hazard, S. Jaouannet, A. Tallec, Bull. (b) A. Guirado, F. Barba, J. Martin, Elec-
Soc. Chim. Fr. 1983, II, 263–264. trochim. Acta 1984, 29, 587–588.
71. G. A. Urove, D. G. Peters, M. S. Mubarak, 98. W. J. M. van Tilborg, R. Plomp, R. de Ruiter

J. Org. Chem. 1992, 57, 786–790. et al., Recl. Trav. Chim. Pay-Bas 1980, 99,
72. G. T. Cheek, P. A. Horine, J. Electrochem. 206–212.
Soc. 1984, 131, 1796–1801. 99. I. Chiarotto, M. Feroci, C. Giomini et al.,
73. G. A. Urove, D. G. Peters, Tetrahedron Lett. Bull. Soc. Chim. Fr. 1996, 133, 167–175.
1993, 34, 1271–1274. 100. A. Inesi, L. Rossi, M. Feroci et al., New J.
74. G. A. Urove, D. G. Peters, J. Org. Chem. Chem. 1998, 22, 57–61.
1993, 58, 1620–1622. 101. P. J. Elving, J. M. Markowitz, J. Electrochem.
75. G. A. Urove, D. G. Peters, J. Electrochem. Soc. 1954, 101, 195–202.
Soc. 1993, 140, 932–935. 102. M. A. Casadei, S. Cesa, A. Inesi, Tetrahe-
76. M. S. Mubarak, G. A. Urove, D. G. Peters, dron 1995, 51, 5891–5900.
J. Electroanal. Chem. 1993, 350, 205–216. 103. F. Maran, J. Am. Chem. Soc. 1993, 115,
77. G. A. Urove, D. G. Peters, J. Electroanal. 6557–6563.
Chem. 1993, 352, 229–242. 104. M. A. Casadei, S. Cesa, F. M. Moracci,
78. G. A. Urove, D. G. Peters, J. Electroanal. Gazz. Chim. Ital. 1993, 123, 457–462.
Chem. 1994, 365, 221–228. 105. C. Giomini, A. Inesi, E. Zeuli, Electrochim.
79. G. A. Urove, D. G. Peters, Electrochim. Acta Acta 1984, 29, 1107–1109.
1994, 39, 1441–1450. 106. S. Kashti, E. Kirowa-Eisner, J. Electroanal.
80. M. S. Mubarak, D. G. Peters, J. Electrochem. Chem. 1979, 103, 119–135.
Soc. 1995, 142, 713–715. 107. S. Kashti-Kaplan, E. Kirowa-Eisner, Isr. J.
81. M. S. Mubarak, J. Electroanal. Chem. 1995, Chem. 1979, 18, 75–79.
394, 239–243. 108. M. S. Mubarak, D. G. Peters, J. Electroanal.
82. J. I. Lozano, F. Barba, Heterocycles 1994, 38, Chem. 1997, 425, 13–17.
1339–1346.
109. R. D. Chambers, W. K. R. Musgrave, C. R.
83. J. I. Lozano, F. Barba, Electrochim. Acta
Sargent et al., Tetrahedron 1980, 37,
1997, 42, 2173–2176.
591–595.
84. F. Barba, M. D. Velasco, A. Guirado, Elec-
110. D. Kyriacou, U. S. Pat. 4,242,183, 1980.
trochim. Acta 1983, 28, 259–260.
111. D. Kyriacou, Chem. Abstr. 1981, 94, 54 933.
85. G. Montero, M. G. Quintanilla, F. Barba, J.
112. V. D. Parker, U. S. Pat. 3,694,332, 1972.
Electroanal. Chem. 1993, 345, 457–461.
113. V. D. Parker, Chem. Abstr. 1972, 77, 164 492.
86. F. Barba, M. D. Velasco, A. Guirado, Syn-
thesis 1984, 593–595. 114. C. K. Bon, A. J. Kemp, T. J. Sobieralski, U.
87. F. Barba, M. D. Velasco, A. Guirado et al., S. Pat. 4,592,810, 1986.
Synth. Commun. 1985, 15, 939–944. 115. C. K. Bon, A. J. Kemp, T. J. Sobieralski,
88. F. Barba, M. D. Velasco, A. Guirado et al., Chem. Abstr. 1986, 105, 69 063.
Electrochim. Acta 1985, 30, 1119–1120. 116. K. Alwair, J. Grimshaw, J. Chem. Soc.,
89. F. Barba, J. L. de la Fuente, Tetrahedron Lett. Perkin Trans. 2 1973, 1811–1815.
1992, 33, 3911–3914. 117. P. Fuchs, U. Hess, H. H. Holst et al., Acta
90. F. Barba, M. G. Quintanilla, G. Montero, Chem. Scand. 1981, B35, 185–192.
Synthesis 1992, 1215–1216. 118. D. Kyriacou, F. Y. Edamura, J. Love, U. S.
91. F. Barba, B. Batanero, J. Org. Chem. 1993, Pat. 4,217,185, 1980.
58, 6889–6891. 119. D. Kyriacou, F. Y. Edamura, J. Love, Chem.
92. A. Kirrmann, P. Federlin, Bull. Soc. Chim. Abstr. 1981, 94, 22 193.
Fr. 1958, 7, 944–949. 120. H. Lund, Acta Chem. Scand. 1964, 18, 1984,
93. P. J. Elving, C. E. Bennett, J. Electrochem. 1995.
Soc. 1954, 101, 520–527. 121. E. Laviron, Bull. Soc. Chim. Fr. 1961,
94. J. P. Dirlam, L. Eberson, J. Casanova, J. Am. 2350–2355.
Chem. Soc. 1972, 94, 240–245. 122. P. E. Iversen, Synthesis 1972, 484–485.
95. A. J. Fry, J. J. O’Dea, J. Org. Chem. 1975, 40, 123. C. Ji, D. G. Peters, J. Electroanal. Chem.
3625–3631. 1998, 455, 147–152.
96. A. J. Fry, A. T. Lefor, J. Org. Chem. 1979, 44, 124. M. Person, R. Mora, Bull. Soc. Chim. Fr.
1270–1273. 1973, 528–536.
97. A. J. Fry, J. T. Andersson, J. Org. Chem. 125. D. Pletcher, M. Razaq, J. Appl. Electrochem.
1981, 46, 1490–1492. 1980, 10, 575–582.
126. R. N. Gedye, Y. N. Sadana, R. Leger, Can. J. 151. C. Amatore, A. Jutand, J. Electroanal. Chem.
Chem. 1985, 63, 2669–2672. 1991, 306, 141–156.
127. S. Dapperheld, M. Feldhues, H. Litterer 152. A. J. Fry, P. F. Fry, J. Org. Chem. 1993, 58,
et al., Synthesis 1990, 403–405. 3496–3501.
128. M. S. Mubarak, D. G. Peters, J. Org. Chem. 153. A. L. Butler, D. G. Peters, J. Electrochem.
1996, 61, 8074–8078. Soc. 1997, 144, 4212–4217.
129. R. M. Justice Jr., D. A. Hall, U. S. Pat. 154. S. Olivero, J. C. Clinet, E. Duñach, Tetrahe-
4,588,484, 1986. dron Lett. 1995, 36, 4429–4432.
130. R. M. Justice Jr., D. A. Hall, Chem. Abstr. 155. S. Ozaki, T. Nakanishi, M. Sugiyama et al.,
1986, 105, 69 060. Chem. Pharm. Bull. 1991, 39, 31–35.
131. H. Lund, M. A. Michel, J. Simonet, Acta 156. S. Ozaki, H. Matsushita, H. Ohmori, J.
Chem. Scand. 1974, B28, 900–904. Chem. Soc., Perkin Trans. 1 1993,
132. S. Margel, M. Levy, J. Electroanal. Chem. 2339–2344.
1974, 56, 259–267. 157. S. Ozaki, S. Mitoh, H. Ohmori, Chem.
133. J. W. Sease, R. C. Reed, Tetrahedron Lett. Pharm. Bull. 1995, 43, 1435–1440.
1975, 393–396. 158. M. A. Semones, D. G. Peters, J. Electrochem.
134. W. E. Britton, A. J. Fry, Anal. Chem. 1975, Soc. 2000, 147, 260–265.
47, 95–100. 159. A. J. Fry, A. H. Singh, J. Org. Chem. 1994,
135. J. Simonet, M. A. Michel, H. Lund, Acta 59, 8172–8177.
Chem. Scand. 1975, B29, 489–498. 160. S. A. Kaufman, T. Phanijphand, A. J. Fry,
136. T. Lund, S. U. Pedersen, H. Lund et al., Tetrahedron Lett. 1996, 37, 8105–8108.
Acta Chem. Scand. 1987, B41, 285–290. 161. D. Pletcher, H. Thompson, J. Electroanal.
B40, 470–485. 162. K. S. Alleman, D. G. Peters, J. Electroanal.
B41, 93–102. 163. A. A. Isse, A. Gennaro, E. Vianello, J. Elec-
139. N. Gatti, W. Jugelt, H. Lund, Acta Chem. troanal. Chem. 1998, 444, 241–245.
Scand. 1987, B41, 646–652. 164. L. J. Klein, K. S. Alleman, D. G. Peters et al.,
140. K. Daasbjerg, J. N. Hansen, H. Lund, Acta J. Electroanal. Chem. 2000, 481, 24–33.
Chem. Scand. 1990, 44, 711–714. 165. M. O. Iwunze, N. Hu, J. F. Rusling, J. Elec-
141. J. Y. Nédélec, J. Périchon, M. Troupel in troanal. Chem. 1992, 333, 331–338.
Topics in Current Chemistry (Ed.: 166. D.-L. Zhou, J. Gao, J. F. Rusling, J. Am.
E. Steckhan), Springer-Verlag, New York, Chem. Soc. 1995, 117, 1127–1134.
1996, pp. 141–173, Vol. 185. 167. H. Hebri, E. Duñach, J. Périchon, Synth.
142. S. Torii, Synthesis 1986, 873–886. Commun. 1991, 21, 2377–2382.
143. M. Durandetti, M. Devaud, J. Périchon, New 168. H. Hebri, E. Duñach, J. Périchon, J. Chem.
J. Chem. 1996, 20, 659–667. Soc., Chem. Commun. 1993, 499–500.
144. S. Condon-Gueugnot, E. Léonel, J.-Y. 169. H. Hebri, E. Duñach, J. Périchon, Tetrahe-
Nédélec et al., J. Org. Chem. 1995, 60, dron Lett. 1993, 34, 1475–1478.
7684–7686. 170. R. S. Wade, C. E. Castro, J. Am. Chem. Soc.
145. M. Durandetti, J.-Y. Nédélec, J. Périchon, J. 1973, 95, 226–230.
Org. Chem. 1996, 61, 1748–1755. 171. A. E. F. Nasser, J. M. Bobbitt, J. D. Stuart
146. M. Oçafrain, M. Devaud, M. Troupel et al., et al., J. Am. Chem. Soc. 1995, 117,
J. Chem. Soc., Chem. Commun. 1995, 10 986–10 993.
2331–2332. 172. K. Yoshida, E. Kunugita, M. Kobayashi
147. M. Durandetti, S. Sibille, J.-Y. Nédélec et al., et al., Tetrahedron Lett. 1989, 30, 6371–6374.
Synth. Commun. 1994, 24, 145–151. 173. K. Yoshida, M. Kobayashi, S. Amano,
148. E. Dolhem, M. Oçafrain, J.-Y. Nédélec et al., J. Chem. Soc., Perkin Trans. 1 1992,
Tetrahedron 1997, 53, 17 089–17 096. 1127–1129.
149. Y. Rollin, G. Meyer, M. Troupel et al., J. 174. K. Yoshida, H. Kuwata, J. Chem. Soc., Perkin
Chem. Soc., Chem. Commun. 1983, 793–794. Trans. 1 1996, 1873–1877.
150. M. A. Fox, D. A. Chandler, C. Lee, J. Org.
Chem. 1991, 56, 3246–3255.
235
9
Electrochemical Reactions of
Sulfur Organic Compounds
Viatcheslav Jouikov and Jacques Simonet

Laboratoire d’Electrochimie Moléculaire et Macromoléculaire, Université
de Rennes I, Campus de Beaulieu, 35042 Rennes, France
9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
9.2 Electrooxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237

9.2.1 Thiones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
9.2.2 Thiols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
9.2.3 Sulfides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
9.2.4 Thioketals and Thioacetals . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
9.2.5 Disulfides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
9.2.6 Tetrathiofulvalenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
9.2.7 Sulfur-containing Polymers . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
9.3 Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256

9.3.1 Thiones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
9.3.2 Sulfides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
9.3.3 Disulfides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
9.3.4 Sulfoxides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
9.3.5 Sulfones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
9.3.6 Sulfonium Salts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
9.3.7 Sulfonamides and Deprotection to Amines . . . . . . . . . . . . . . . . . 268
9.4 Sacrificial Sulfur Electrodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268

9.4.1 Sacrificial Anodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
9.4.2 Sacrificial Cathodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
237
9.1 conjugation or other interactions affect-

Introduction ing the delocalization of a charge on the
sulfur atom. The HOMO of such in-
Sulfur organic compounds were among termediates still controls their reactivity,
the first that attracted the attention of which is the tendency to dimerization or
electrochemists about a century ago. Since other second-order orbital-controlled in-
that time, great progress has been made in teractions. The lack of conjugation, for
this field and it will not be an exaggeration example, in aliphatic sulfur derivatives,
to say that synthetic and theoretical studies causes sulfur-centered charge-controlled
in sulfur electrochemistry account for a reactions and often results in scission of
great part of the progress in organic bonds formed by sulfur. If sulfur does not
electrochemistry. form multiple bonds or has no vacant or
An enormous amount of work has been half-filled orbitals, like in sulfonium salts,
done in this wide field and a number the reduction of such compounds is usu-
of excellent reviews on different aspects ally accompanied by reductive cleavage.
of sulfur electrochemistry has been pub- The review below deals with anodic
lished [1–7], so here we confine our at- and cathodic reactions of organic deriva-
tention to some principal reactions and tives of sulfur, which have interesting
interesting applications of both anodic and potentialities for the electrosynthesis and
cathodic activation of sulfur-containing electrochemically initiated functionaliza-
molecules. Compared to other chalco- tion of organosulfur and related or-
genides, sulfur has frontier orbitals that ganic compounds.
have volume, symmetry, and energy more
suitable for efficient interaction with ad-
jacent carbon atoms. The ionization of
9.2
molecular sulfur requires about 10 eV. Electrooxidation
Conjugation of the pz orbitals of sulfur
with a π-system lowers the ionization 9.2.1
potential by ca. 2 eV. For this reason, Thiones
compounds of divalent sulfur undergo
oxidation rather easily often giving rise The HOMO of thiocarbonyl compounds
to cation radicals or dications. The sta- corresponds to the n-electrons of sulfur;
bility of this species is in line with the the π-orbitals of the C=S bond usually
238 9 Electrochemical Reactions of Sulfur Organic Compounds
have a lower energy. However, both chem- intermediates (a free radical and the cor-
ical (shown for thioureas, thiocarbonates, responding highly reactive cation). The
and thiocarbamates) and electrochemical anodic behavior of alkyl isothiocyanates
oxidation (tested for aromatic thiocarbonyl appears to be strongly dependent on the
derivatives in poorly nucleophilic media) bulkiness of the alkyl group R. As a mat-
show reaction of C=S double bond open- ter of fact, the exclusive formation of
ing and formation of dicationic dimers five-membered heterocyclic compounds as
(Eq. 1) [8]. shown in Structures (1), (2), and (3) implies
reactions of transient(s) with the start-
R1 R1 R1
ing compound or the nucleophilic solvent
−2e− + +
2 C S C S S C (in the example quoted above, acetoni-
trile will favor formation of structure (1))
R2 R2 R2
(Scheme 2).
(1) The anodic oxidation of 1,2-dithiole-3-
The oxidation step of thioureas can be thiones (R1 , R2 = H, Ph, respectively) was
reversed, as was shown by cyclic voltamme- reported [9, 10] to yield disulfide-linked
try to regenerate thiourea from anodically bis(dithiole-3-thione) dication (Scheme 3).
produced dimeric salt (in AN/Bu4 NClO4 , Homogeneous oxidation of sub-
potentials vs Ag/Ag+ ) (Scheme 1). stituted thiobenzamides and N ,N -
The anodic oxidation of alkyl isothio- diphenylthiourea in aqueous AN/Bu4
cyanates RNCS in wet acetonitrile (AN) NOAc or in aqueous EtOH/Et4 NOTs,
involves the formation of two possible mediated by the organotellurium species
+ +
R2N R2N NR2
−2e (E = 0.5 and 0.8 V)
2 C S C S S C
+2e (E = 0.5 V)
R2N R2N 2 ClO4− NR2
Scheme 1 Anodic dimerization of thiourea and cathodic cleavage of the dimer.
OH OH
−e− H2O −e−
RNCS [RNCS] • +
−H+ RN • S RN + S
CH3CN 2X
2X
R O R O
N C S S N C
MeC S RN C C O C S
N N N
S
R R
(1) (2) (3)
Scheme 2 Anodic oxidation of alkyl isothiocyanates.

9.2 Electrooxidation 239
S S S S S S
2 −2e− + +
R2 S R2 S S R2
R1 R1 R1
Scheme 3 Anodic oxidation of 1,2-dithiole-3-thiones.
S Ph
−e N
Ph C NH2 Ph CN +
Ar2Te N
Ph S
Scheme 4 Oxidation of substituted thiobenzamides.
generated by the electrooxidation of when pH > pKa (RSH), the only form,
diorganyltellurides, results in substi- RS− , is present, and the Ep remains
tuted benzonitrile and 3,5-diaryl-1,2,4- constant. The oxidation of thiols at a Hg
thiadiazole [11]. The use of the first solvent electrode occurs reversibly (in acid media)
favors the formation of nitriles whereas and involves the formation of a metastable
by using the second electrolyte, the cor- intermediate of Hg(I) (Eq. 2):
responding thiadiazoles were selectively
obtained in a 71–77% yield (Scheme 4). −e
(2)
The oxidation of thioesters of phospho- RSH + Hg RSHg + H+
rus(III) acids (S-ethyldiphenylphosphi-
nite, S,S-diethylphenylphosphonite and Then mercury thiolate transforms into
triethylthiophosphite) in AN/NaClO4 oc- a more stable Hg(II) derivative (Eq. 3)
curs at potentials characteristic for [16, 17].
thioethers with substituents other than
for phosphorus(III) groups, which sug- 2 RSHg (RS)2Hg + Hg (3)
gests the contribution of the lone pair
of sulfur to the HOMO to be predomi- The oxidation of thiols on mercury and
nant. The process is thought to proceed some other metals (M = Zn, Cd) can be
via an intermediate cation radical with the used for the preparation of different bis-
number of electrons n varying from 0.65 thiolate complexes M(SR2 ) [18].
to 0.85, which suggests a catalytic mecha- Under aprotic conditions, prototropic
nism [12–15]. transformations of thiols are relatively
slow, so one can observe distinct waves
9.2.2 of the oxidation of the protonated form
Thiols and of its parent base [19, 20]. Normally,
the oxidation of thiols (aliphatic, aromatic,
In aqueous solutions, the peak potentials and heteroaromatic) affords diorganyl-
of the oxidation of thiols vary with disulfides. So various aliphatic and aro-
pH (Ep /pH ∼ = 60 mV), reflecting the matic thiols are easily converted into the
position of the acid-base equilibrium corresponding disulfides upon oxidation
affecting the SH group. In basic solutions, in MeOH/MeONa with the yields ranging
from 65 to 95% (Eq. 4) [21]. the deprotonated form [25]. The overall
process can be depicted by the following
−e
RSH 1/2 RSSR (4) Scheme 6.
−H+ The system lipoic-dihydrolipoic acid
The electrooxidation of thiophenol [19], behaves in a similar way.
2-mercaptobenzothiazole [22], 6- and 2- Although thiophenol, like other thiols,
thiopurine [23], 2-thiopyridine [24] results normally forms diphenyldisulfide upon
in their disulfide derivatives in good yields. oxidation [19], in the presence of a strong
Bifunctional compound, 2,6-purinedi- proton-donor (CH3 NO2 /CF3 COOH) it can
thiol [23] can form first a 6,6 -disulfide (4), undergo anodic polymerization to give
and then, by subsequent oxidation of the poly-p-phenylene sulfide (Eq. 5) [26].
latter, give a cyclic product with two S–S
SH
bridges (Scheme 5).
−2n e (5)
In the anodic process of another bifunc- S
n −2n H+
tional thiol, 1,3-propanedithiol, all three n
forms – a neutral molecule, its mono-, and
dianion undergo oxidation. The addition Another example of a polymer formation
of HO− ions to the solution or a ca- is the oxidation of 1,3,4-thiadiazole-2,5-
thodic preelectrolysis (due to the reduction dithiol [27] including the formation of an
of protons), shift the equilibrium toward intermediate disulfide (5). As the latter is
SH S S
N −e N N
N 1/2 N N
−H+
HS N N N N SH HS N N
H H H
(4)
S S
−2e N N N N
4
−2H+
N N S S N N
H H
Scheme 5 Anodic cyclodimerization of 2,6-purinedithiol.
CH2SH CH2S− CH2S−

+e +e
H2C H2C H2C
−1/2 H2 −1/2 H2
CH2SH CH2SH CH2S−
−2e −2e −H+ −2e

+
−2H CH2S
H2C
CH2S
Scheme 6 Anodic cyclization of 1,3-propanedithiol.

easier to oxidize than the starting thiol, or 11-mercaptoundecanoic acid) [37], a

it forms a polymer in the presence of 2- viologen derivative of N -(n-octyl)-N -
chloro-pyridine or lutidine (Scheme 7). (10-mercaptodecyl)-4,4 -bipyridinium di-
Anodic fluorination of thiols was re- bromide [38], and 3,3 -thiodipropionic
ported [28] providing a route to perfluo- acid [39] form monolayers on the gold elec-
roalkyl derivatives of sulfur hexafluoride trodes by self-assembly. Polybithiophene
though the yields of products are not films were electrochemically grafted onto
high. The process, achieved in a system titanium electrodes as well [40].
of HF/NaF at a Ni anode with helium
bubbling through the solution, leads to dif- 9.2.3
ferent perfluorinated products (Scheme 8). Sulfides
The high tendency of thiols to form
sulfur-gold bonds upon oxidation on a First reported by Fichter in the year
gold electrode was used in numerous 1910 [41–52], and improved later on as
investigations to modify gold electrodes described in many papers and patents, the
for different analytical and synthetic pur- oxidation of diorganylsulfides in aqueous
poses. Nonanethiol [29], butanethiol and and organo-aqueous media occurs in two
octanethiol [30], hexadecanethiols [31], oc- steps, providing first sulfoxides and then
tadecanethiol [32], ferrocene-terminated sulfones in yields close to quantitative
alkanethiol (FcCO2 C11 H22 SH) [33], 2- (Eq. 6).
mercaptobenzothiazole and 2-mercapto-
O
benzimidazole [34], 3-mercaptopropionic
−2e O −2e
acid or bis(4-pyridyl) disulfide and RSR′ RSR′
H2O, −2H+ H2O, −2H+
n-alkanethiols having various chain RSR′
lengths [35], 4-aminothiophenol [36], 1- O
undecanethiol and 3-mercaptopropionic (6)
acid (the latter can be selectively removed Diverse products were obtained when
by controlling the electrode potential, performing this process under water-free
and replaced with 1-hexadecanethiol conditions. The fact that the removal
N N −e N N N N
1/2
HS
S SH −H+ HS
S S S SH
(5) S
−e N N N N N N
5 +
Py/PyH HS S S S S SH
S S S
n
Scheme 7 Anodic polymerization of 1,3,4-thiadiazole-2,5-dithiol.
F2
∼30 F mol−1
C
F2 C
HS(CH2)4SH F5S(CF2)4SF5 + C4F9SF5 + SF4
Ni anode F2C C
HF/NaF F2
Scheme 8 Anodic perfluorination of 1,4-butane-dithiol.

of an electron from organic sulfides The cation radicals of the compounds

normally provides intermediate sulfur with electron-withdrawing substituents
cation radicals helps to better understand undergo first-order sulfur-centered re-
the nature of the transformations leading actions (Scheme 9) [48–50], those with
to these products. neutral or weak donor substituents
The reactions of electrogenerated cation (Scheme 10) react with π-nucleophiles
radicals of diarylsulfides are mainly orbital- such as styrene, anisole [51, 52] to give
controlled and at this level the elec- trisarylsulfonium salts (if the p-position is
tronic structure of their frontier orbitals substituted [52]) or Ph2 S+• can dispropor-
(HOMO–SOMO) has very interesting syn- tionate (Scheme 11). The cation radicals
thetic consequences. The 3p orbitals of of arylsulfides bearing electron-donating
sulfur are conjugated with only one aro- substituents can form more reactive di-
matic ring even if there are two aryls bound cations by disproportionation, which, in
to sulfur. Therefore, only one ring can be turn, can react with nucleophiles [52, 53].
activated electrochemically. The degree of In the absence of an external nucleophile,
the charge delocalization in the ArS moiety the sulfides produce sulfonium products
of a cation radical on the one hand, and by self-coupling (Scheme 11) [48, 52–56].
the availability of p- and o-positions for the When the para-position of an aromatic
substitution on the other, determine quite ring is substituted, ortho-products can
different reactivity of such species. be obtained, the regioselectivity of their
O
−2e
O2N S NO2 O2N S NO2
Wet AN
Scheme 9 Oxidation of diorganylsulfides in organo-aqueous media.
−e TolH
Tol 2S Tol 2S+• Tol 3S+
−e, −H+
Scheme 10 Generation of sulfonium salts from thioethers.
−e
Ph2S Ph2S+•
2 Ph2S+• Ph2S + Ph2S++
Ph
Ph2S +
S C6H4SPh
−H+
[Ph2 S]++ Ph
2 R − Py + R
PhSC6H4 N
−R − Py+H
Scheme 11 Formation of sulfonium and pyridinium products by anodic oxidation of Ph2 S.

formation is controlled by the combined Different nucleophiles such as methanol,

electron-donating effects of the para- allylsilanes, silyl enol ethers, trimethylsilyl-
substituents [57]. cyanide, and arenes can be used in this pro-
The sulfonium dimer can in turn be cess [62]. When the sulfide itself contains
oxidized at a higher potential, which is an unsaturated or aromatic fragment and
the diffusion-limited oxidation current of the process is carried out in the absence of a
Ph2 S. For this reason, the concentration nucleophile, an intramolecular anodic sub-
of the latter in the reaction layer closer stitution/cyclization might occur [61–63].
to the electrode is practically zero, so Methyl esters of 2-benzothiazolyl-2-alkyl
a dimeric dication radical formed from or aryl-acetic acid, oxidized in MeOH/Et4
[(Ph)2 S-C6 H4 SPh] can only react with NClO4 or H2 SO4 in the presence
this cation. Thus, no trimers but only of CuCl2 , form 2,2-dimethoxy products
tetramers are obtained under such con- (Eq. 7) [64].
ditions (Scheme 12) [52, 54, 55].
OMe
Alkyl aryl sulfides [48, 56–59] follow the R′ CO2Me −3e
R′ CO2Me
same scheme of oxidation, that is, sul- MeOH, −H+
S R′′ OMe
fonium dimers are the main products
unless the alkyl group is a stable-leaving (7)
group (i-Pr, CH2 Ph, CPh3 ), in the last Oxidation of α-organylthiocarbamates in a
case, an S−C(sp3 ) bond cleavage occurs MeOH/Et4 NOTs system smoothly affords
(Scheme 13). the substitution of the ArS-group with
Oxidative S−C bond cleavage, fol- MeO; the yields of such a process are
lowed by the attack of a nucleophile close to quantitative [62]. The eliminating
on the carbocation formed, is a classi- ArS• fragment dimerizes to end up as a
cal anodic substitution reaction. In this corresponding disulfide (Scheme 14).
way, OH [60], AcNH [61], AcCH2 [62], Anodic elimination (oxidative desul-
and CH2 =CHCH2 [63] groups were in- fanylation–deprotonation) occurs when a
troduced to replace the RS fragment. carbonyl or CN group (X) is attached
Ph Ph Ph Ph
+ −2e + + +
2 S C6H4SPh S C6H4SC6H4 S SPh
−H+
Ph Ph C6H4
Scheme 12 Anodic coupling of a sulfonium dimer.
R
Self-coupling
Ph S SR
PhSR, −e, −H+ +
−e +• S C cleavage
PhSR PhSR PhSSPh + 2 R+
C H cleavage PhS R′
R R′C(H)1-2
Nu, −H+ Nu
Scheme 13 Different pathways of oxidation of alkyl aryl sulfides.

X X′
CO2Me −2.3 − 2.9 F mol−1 CO2Me
Ph N Ph N
MeOH
CH2Y CH2Y′
X, Y = H, SPh X′, Y′ = H, OMe
SPh, H OMe, H
Scheme 14 Anodic oxidation of thiocarbamate.
to the β-carbon rendering its proton(s) observed [67].

more acidic. α,β-Unsaturated carbonyl or PhS R′ OAc R′
cyano derivatives can thus be obtained −2e
PhS
(Eq. 8) [65]. R AcOH/AcONa
R
R −2e (9)
X R X When there is an Me3 Si group at the α-
−H+
SEt
position of an alkyl aryl sulfide, which
(8) is known to leave more easily than a
A simultaneous cleavage of both C−S and proton, the cleavage of the Csp3 −Si bond
C−C bonds was observed during the ox- gives access to different α-functionalized
idation of β-hydroxysulfides [66] resulting products (R=RCO, or, RR1 C=CHCHR2 )
in two different ketones (Scheme 15). (Scheme 16) [71–73]. However, in a low-
The last reaction in Scheme 13 be- nucleophilic media, it is the rupture of the
comes possible when the sulfide has a S−C(sp3 ) bond that takes place leading
CH2 or CH fragment, adjacent to the to corresponding disulfides in an EC2 C1
sulfur atom whose protons are getting process [73].
more acid when the molecule is oxidized. Both the second and third processes
Electron-withdrawing groups (EWGs) in- in Scheme 13 can also be used for
crease the ease of deprotonation of this site the functionalization of α-silylated alkyl
even more. Thus, α-MeO–, α-AcO–, and phenyl sulfides [74] when oxidizing the
α-F-sulfides were prepared (Eq. 9) [67–70]. latter in the presence of primary alcohols.
When the nucleophilic attack is sterically First, the cleavage of the C−Si bond
hindered or α-protons are absent, prod- (equivalent to deprotonation) and then
ucts acetoxylated in the phenyl ring are that of the S−C bond occurs to give
OH SR −2e
R1 R4 R1R2C O + R3R4C O
MeOH or
R2 R3 AN/H2O
Scheme 15 Anodic oxidation of β-hydroxysulfide.
RO−
ArSCH2OR + Me3SiOR
−2e
ArSCH2SiMe3
ArSSAr + Me3SiCH2+
Scheme 16 Anodic oxidation of α-trimethylsilylmethylene aryl sulfide.

either 1-methoxy-1-phenylthioacetone or Anodic regioselective fluorination of

its acetal (Scheme 17). α-phenylsulphenylated ethyl acetates, 1-
Anodic nucleophilic functionalization of naphthalene and 2-pyridine deriva-
an α-carbon turned out to be particularly tives [80], 1-aryl-3-(phenylthio)oxindoles
efficient for the fluorination of organic and 2-substituted-3-oxo-4-(phenylthio)-1,2,
sulfides. The introduction of one or two flu- 3,4-tetrahydroisoquinolines [81], 2-benzo-
orine atoms at the α-carbon was reported thiazolyl and 5-chloro-2-benzothiazolyl
in several papers for sulfides bearing sulfides [82], α-(phenylsulfenyl)lactams
EWGs = CN, COMe, COPh, CF3 , CO2 Et, [83], as well as various heterocycles
CONEt2 , PO(OEt)2 ) (Scheme 18) [75–78]. such as thiolanones, oxathiolanones, dithi-
Two systems are mainly used as the sup- olanones, 3H-1,4-benzoxathian-2-ones [84]
porting electrolyte and fluorine source at a in Et3 N·3HF or Et4 NF·nHF (n = 3,4), has
time namely, Et3 N·3HF and Et4 NF. been reported.
Both mono- and difluorination of aro- The anodic fluorination of 2-phenylthio-
matic thioethers can be achieved for chromen-4-one under similar conditions
compounds bearing an electron acceptor provides 3-monofluoro- and 2,3,3-trifluoro-
group, not only at the α-methylene carbon products (Scheme 20) [85].
but also in the aromatic ring (EWG = CN, Recent developments in anodic fluorina-
NO2 , RSO2 ) (Scheme 19) [79]. tion were reviewed in Ref. [86].
SPh SPh OMe

−2e −2e
R R R
MeOH MeOH
SiMe3 OMe OMe
Scheme 17 Anodic substitution of α-silylated alkyl phenyl sulfides.
−2e, −H+
ArSCHF EWG
ArSCH2 EWG
Et3N• 3HF −4e, −2H+
ArSCF2 EWG
Scheme 18 Anodic fluorination of sulfides.
EWG
−2e, −H+
SCHF R
EWG
SCH2 R
Et3N• 3HF
−4e, −2H+ EWG
SCF2 R
Scheme 19 Anodic fluorination of sulfides.
O O
F
−2e
Et3N• 3HF/AN
S Ph S Ph
Scheme 20 Anodic fluorination of thiochromen-4-one.

The preparative oxidation of vinyl sul- that described in Ref. [87] was proposed
fides is thought to proceed via an interme- involving a thiiran intermediate, formed
diate bridged sulfonium cation that can be upon addition of a first Nu to the vinylic
attacked by an external nucleophile from cation radical, which can then be attacked
the less encumbered side to give two iso- by a second Nu from either side to give
mers (Scheme 21) [87]. either gem- or vic-adducts.
As performed in AN, with either Oxidative electrophilic activation of α,β-
H2 O or MeOH added [87, 88], this pro- unsaturated phenylsulfides, carried out
cess can afford different products, for in an AcOH/AcONa solution results in
example α-thioaryl aldehydes or their products of the addition of a nucleophile to
dimethyl acetals. Similar products were the multiple bonds, α,β-diacetoxysulfides
shown to form in systems AN/Et3 N·3HF, or, as a result of a further oxidation, that
MeOH/Et3 N·3HF, and AcOH/AcOK, the eliminates the PhS group, in α-acetoxy
nucleophiles being F, MeO, and AcO, ketones (Scheme 23) [89].
respectively. In the last two cases both Although the oxidation of arylsulfides, as
vicinal and geminal adducts were obtained determined by their HOMO’s structure, is
(Scheme 22). expected to involve cation radical species,
In order to rationalize the product these latter reactions are not always
distribution, a mechanism analogous to detectable by voltammetry at reasonable
R1 R2
R2 a R1C(O) CHR2SR3
C C
−2e, −2H+
R1HC C +
S
b R1CHSR3 C(O)R2
SR3 a b
R3
OH−
Scheme 21 Anodic oxidation of vinyl sulfides.
R
−2e O
H2O SAr
SAr
Nu Nu
R
−2e R R
Nu SAr
Nu SAr Nu
R AcO R AcO R′
−2e
SPh or
SPh AcOH/AcONa
Alk Alk OAc Alk O
R = H, AcOCH2, CO2R

sweep rates. The presence of an extended effect, anchimeric assistance or interaction

conjugated system is crucial for the through space) are repulsive and
stability and hence the observation of destabilizing for the starting molecule
such cation radicals: for example, the so they lower its oxidation potential by
reversibility was not seen for the oxidation splitting the levels of the occupied frontier
of the first two naphthalene derivatives orbitals. On the other hand, they strongly
(6) and (7) depicted below [90], whereas stabilize the corresponding cation radicals
it was observed for derivatives (8) to due to the interaction that can vary from
(10) [91, 92]. In some cases, even if at almost purely electrostatic to two center,
moderate scan rates the reduction signals three electron [2c3e]- or 2e-bonds. The
of cation radicals or dications from PhSR formation of stable dithiadications of 1,5-
(R = Me, Et, i-Pr, t-Bu, Ph) are not seen; dithiacyclooctanes is, probably, the best
these species, however, were successfully illustration of this [90, 101, 102].
used to mediate the oxidation of secondary Anodic oxidations of hexathioalkyl ben-
alcohols to ketones [93]. zene asterisk compounds were achieved
The assistance of some electron-rich at a Pt anode in AN. In particular, hexa-
groups [94–96], heteroatoms [90, 97, 98] iso-propylthio-benzene afforded both the
or filled σ -orbitals [99, 100] in the oxidation primary cation radical and the free radical
of organic sulfides was studied in a obtained from the deprotonation (Eq. 10).
series of papers (Scheme 24). Since the The radical was found to exist in two forms
3p orbitals of sulfur are quite compact (one progressively transformed into an-
compared to those of Se, the mentioned other as evidenced by ESR spectroscopy).
electronic and stereoelectronic effects are The observation of both forms was possi-
rather remarkable. These interactions ble because of a sterically caused hindered
(discussed in terms of a trans-annular rotation. The produced free radical has
S S
MeS SMe S S S S S S S S
(6) (7) (8) (9) (10)
−e +•
R S R′ R S R′
Y Y
Y = O, S, Se, N, P - containing groups
C—C, C—Si, C—Sn bonds
Scheme 24 Neighbouring group assistance of sulfide oxidation.

quite a long half-time life (τ1/2 > 200 s) at dimeric dication. In the presence of water,
room temperature [103]. an ECE process takes place involving the
cleavage of two S−C bonds and leading
H3C • CH3
to a disulfide and a carbonyl compound
SPri S (Eq. 12) [107].
i-PrS SPri i-Pr Pri
−e−
R S R
−2e S
−H+ +
i-PrS SPri i-Pr Pri AN/H2O
O
S
SPri Pri R1 S R1
(10) (12)
This process is more efficient when be-
9.2.4 ing redox-catalyzed [110, 111]. Thus the
Thioketals and Thioacetals use of electrogenerated cation radicals
of some triarylamines (Ar = Tol, p-Br-
The oxidation of geminal dithioethers C6 H4 [112]) as mediators provides even
usually results in the removal of both higher yields of the corresponding car-
organylthio groups affording a disulfide bonyl compounds.
and regenerating a ketone or an alde- In wet acetonitrile, 1,3-dithiane-1-oxides
hyde. Since the thioprotection of carbonyl can be formed from 1,3-dithianes (Eq. 13)
groups is a common tool in organic synthe- [105, 107].
sis, this process received special attention
as a general and selective way of depro- O
tection of various carbonyl compounds. R S −2e, −H+ S (13)
Open-chain bis(diorganylthio)methanes, Nu OH
R1RC
substituted 1,3-dithianes, and related R1 S S
compounds [104–109] can be converted
into corresponding carbonyl compounds The formation of S-oxides has also been
(Eq. 11); it is also possible to deprotect observed when oxidizing a variety of
a ketone thioacetal in preference to an 5-substituted 2-tert-butyl-1,3-dithianes in
aldehyde thioacetal [108]. wet acetonitrile. In an undivided cell,
4-substituted 1,2-dithiolane-1-oxides were
ArS −2e obtained (Scheme 25) [113]. A coupled ca-
ArSSAr + O CH2 (11)
ArS
AN/H2O thodic process, in this case, was the
reduction of protons formed in the an-
In dry AN, the oxidation was shown to odic reaction.
follow an EEC scheme (electrochemical, Under the conditions of electrochemical
electrochemical, chemical reaction) and carbonyl deprotection, some strained
is thought to involve an intermediate cyclic systems like 2-, 2,2-, and
O
S S X
R X −4e
+ RR1C O
R1 Y AN, H2O Y
S S
Scheme 25 Conversion of 1,3-dithianes into 1,2-dithiolane-1-oxides.

SPh
+•
Me SPh
SPh Me OMe SPh
−e SPh
Me SPh
Me AN/MeOH (44%)
SPh
• +
+ OMe O
Me S
Me OMe
Ph
(33%)
Scheme 26 Anodic ring opening of 1,1-bis(phenylthio)-cyclopropanes.
2,3-methylsubstituted 1,1-bis(phenylthio)- The oxidation of diphenyldisulfide in

cyclopropanes undergo ring opening AcOH/HCl or AN/NaClO4 [115] solution
to give methanol-addition products gives benzenesulfonic acid or its sodium
(Scheme 26) [114]. The process is thought salt (Eq. 14) [116, 117].
to include an intermediate equilibrium of
two distinct cation radicals, so the presence PhSSPh
Pt anode
PhSO3Na (14)
of donor methyl groups at the C(2) atom, AN/NaClO4
stabilizing the cation radical, is critical for
the ring opening. Using this reaction, 1-cystine was con-
verted to 1-cysteic acid; the process gives
9.2.5 better yields when mediated by bromide
Disulfides ion oxidation [118].
In wet acetonitrile, the oxidation of
Being oxidized in the presence of oxy- diaryldisulfides [119] and dialkyldisulfides
gen donors such as ClO4 − or in aqueous (Alk = t-Bu) [120] affords the correspond-
solutions, diorganyldisulfides often cleave ing aryl and alkylthiosulfonates in good
the S−S bond to form corresponding sul- synthetic yields (Eq. 15). Thus, the oxi-
fonic acids. In wet acetonitrile (AN), other dation of a cyclic disulfide, dibenzo(c,e)-
oxygen containing products, for example, 1,2-dithiin (1,1) does not affect the S−S
sulfones, were obtained as well. However, bond and results in a corresponding
under dry aprotic and low-nucleophilic thiosulfonate, dibenzo(c,e)-1,2-dithiin-1,1-
conditions, the rupture of the S−S bridge dioxide(Scheme 27) [121]. Such oxidized
occurs to produce RS+ species that can products can form in wet acetonitrile
react with a variety of C-nucleophiles pro- as well as in a dry solvent, but in
viding a convenient route to different the latter case this is probably a re-
organo-sulfur derivatives. sult of disproportionation of the primarily
−2e, −3H+
+ 11
H2O
S S S S S S
O
(11)
O O
Scheme 27 Oxidation of disulfide to diaryl thiosulfonate.

formed sulfoxide. been illustrated by the oxidation of un-

symmetrical dichalcogenides (both due
−4e
RSSR RSO2SR (15) to the different substitution at the aro-
AN-H 2O/NaClO4
matic rings or to the different nature
of heteroatoms forming the dielement
When neither solvent nor supporting salt bridge). It was shown that unsymmetri-
can provide oxygen (e.g. in a system cal diaryl disulfides, like 4-bromo-4 -nitro-
CH2 Cl2 /Bu4 NBF4 ) and a strong proton diphenyldisulfide, or a heterodielement
donor is present in the solution, the compound like phenylselenylthiobenzene,
oxidation of diphenylsulfide yields oligo(p- PhSSePh, undergo symmetrization to
phenylene)sulfides (Scheme 28) [122]. give a mixture of two symmetrical di-
In an aprotic solution, the mechanism aryl disulfides, 4-4 -dibromo and 4,4 -
of oxidation of diaryl disulfides was shown dinitrodiphenyldisulfide (in a total yield
to be more complex than a direct cleav- 80%) or, respectively, diphenylsulfide and
age of the S−S linkage [116, 117, 123]. diselenide (Scheme 29) [116, 117].
The occurrence of two consecutive re- Owing to a very dissymmetric π-charges
actions being of second kinetic order if distribution on the S−S bridge in aryl
potential-determined and of first order if methyl disulfides, 4-RC6 H4 SSMe, the
current-determined, was established for cation radicals of these compounds behave
the two-electron transfer steps. Dimer- like those of alkyl aryl selenides, undergo-
ization of the cation radicals occurs on ing a potential-determined cleavage of the
the ArS fragment, whose contribution S−S bond or a deprotonation of the methyl
to the HOMO is more important, and group [124, 125].
produces an intermediate disulfonium di- Electrogenerated organylsulfenium cat-
cation. The subsequent cleavage of the ions RS+ , being strong electrophiles, pro-
latter results in two ArS+ cations and a vide interesting synthetic opportunities
molecule of a disulfide (the same as a start- for the sulfur functionalization of organic
ing disulfide in the case of symmetrical compounds. First reported by Bewick [126]
compounds). This mechanism, EC2 C1 E for Me2 S2 , the oxidation of diorganyldisul-
(E = electrochemical, C = Chemical), has fides in an appropriate aprotic solvent (AN,
+•
−e PhSSPh
PhSSPh PhSSPh C6H4 -S
n
Scheme 28 Anodic oligomerization of diphenyldisulfides.
−e +•
ArSSAr1 ArSSAr1
+
+•
k2 ArS SAr1 k1
2 ArSSAr1 ArSSAr + 2 Ar1S+
ArS SAr1
+
Scheme 29 Anodic symmetrization of unsymmetrical dichalcogenides.

CH2 Cl2 , sulfolane, THF) in the presence of 1,2-dimethylthiation was obtained in a

alkenes, whose oxidation potential is lower quantitative yield (Scheme 31) [128].
than that of the disulfide, results in the Terminal alkenes, containing ω-OH or
addition of the MeS group on the double ω-COOH functionalities, may undergo
bond. Since then, the anodic sulfeanylation cyclization [129] with different orienta-
of multiple bonds received many synthetic tion of the intramolecular attack of
applications. the nucleophilic end of the molecule
High selectivity of the addition and the on the intermediate episulfonium ion
formation of trans-products (with an ex- (Eq. 16).
ternal nucleophile added to the vicinal
position to RS group) suggest that the PhSSPh
OH PhS
process occurs via an intermediate episul- 1-2 −2e 1-2
O
fonium complex or an ylide (Scheme 30).
The nucleophilic properties of the me- (16)
dia are crucial for the nature of the Usually, 5- and 6-membered Markovni-
methylthio products formed. With pyri- kov-type products are formed; in other
dine, a product of vicinal methylthiation- cases the process results in various open-
pyridination was obtained. In pure ace- chain products. The formation of an
tonitrile the solvent itself plays the role anti-Markovnikov adduct from 2-cyclohex-
of a nucleophile [127], whereas in a low- 1-enyl-ethanol was explained by the cy-
nucleophilic liquid SO2 a product of clization of an episulfonium intermediate
−2e
Me2S2 2 MeS+
Me S+
MeS
Nu−
MeS+ + or
+ Nu
Me S
Scheme 30 Sulfenylation of double bonds.
SMe
Pyridin
AN +
N
SMe
MeS+
AN
NHCMe
SMe O
Liquid SO2
SMe
Scheme 31 Addition of the methylthiogroup and nucleophiles to alkenes.

into a spiro compound with a 4-membered external nucleophile (Eq. 18).

O-containing ring, which then rearranges
to the more stable 5-membered product Br
(Eq. 17) [129]. −2e
(CH2)2S 2
Et4NBr
1-2 2 1-2 S
SAr
(CH2)2OH (18)
ArSSAr
The oxidation of Me2 S2 in the presence
−2e
O of aromatics with an increased electron
Ar Ph, MeO C6H4
density at several carbons, such as ace-
naphthylene or phenanthrene, and pyri-
(17) dine leads to similar products of vicinal
The process was shown to be functionalization (Scheme 32) [128].
more efficient when performed in The feasibility of a one-pot consecutive
the presence of some bromide salts removal of the pyridinium moiety by
whose oxidation allows lowering of reducing the products electrochemically
the working potential and favors the in the same cell has been shown, thus
S−S bond scission. Bromide mediated providing a convenient synthetic route
oxidation of bis(2-cyclopent-1-enylethane) to 1-methylthio-acenaphthylene and 9-
and bis(2-cyclohex-1-enylethane)disulfide methylthio-phenanthrene (Eq. 19) [128].
in AN/Et4 NClO4 /Et4 NBr [130] undergoes
the S−S bond cleavage followed by an
intramolecular attack of the sulfenium
+2e
cation on the double bond to give [3.3.0] 7 (19)
and [4.4.0] bicyclic products. The anion −PyH+
Br− also serves in the process as an MeS
+
MeS N
MeS+ +
Py
MeS+ +
Py +
N
MeS
(7)
Scheme 32 Addition of the methylthiogroup and nucleophiles to aromatic compounds.

O
−2e R1 −4e SR
RSSR + R1
R1 C CH S H2O, −5H+
R O
R = Ph, Tol, PhCH 2
R1 = Ph, n-Bu
Scheme 33 α-Oxothioesters by addition of electrogenerated RS+ electrophiles to alkynes.
RS+ electrophiles that are electrogener- anisoles in 26 to 77 and 11 to 35% yields,

ated in a CH2 Cl2 /Bu4 NClO4 solution read- respectively (Eq. 20) [133].
ily attack even less reactive triple bonds
X X
of terminal alkynes [123] and result, after
R R R R
further oxidation and hydrolysis, in α-oxo-
MeS+ +
thioesters (Scheme 33). Under acidic con- −H+
ditions, it is possible to direct the reaction
SMe
to the formation of an oligomer, cyclohexa- X = OH, OMe
1,4-phenylene sulfide, or a conductive (20)
poly(p-phenylene)sulfide [131, 132]. When anthracene was used as an
For electrogenerated sulfenium cations, arene under similar conditions, a mixture
not only the addition to multiple car- of methylthiated products was obtained,
bon–carbon bonds was shown but also among them 9-methylthio-anthracene (12)
examples of electrophilic aromatic substi- in 74% yield, and the dimer of (12)
tution. Carried out in a low-nucleophilic (Scheme 34) [128].
media (CH2 Cl2 ), this process provides a To circumvent the limitation caused
new route to arylthio derivatives allow- by the oxidation of aromatic substrates,
ing methylthiation of diverse phenols and a two-step process was designed in
SMe SMe MeS SMe
−2e
Me2S2 + +
Anthracene
SMe MeS SMe

(12)
SMe
O
+
SMe
Scheme 34 Methylthiation of anthracene.

such a way that Me2 S2 is first The resulting t-BuSS• radicals dimer-
oxidized in liquid sulfur dioxide ize to the tetrasulfide, and t-Bu+ car-
to generate a potent methylthiating bocation can be trapped by different
agent, supposedly (MeS)3 + , which can nitriles to afford, after workup, corre-
be isolated as a solid with an sponding N -(t-Bu)amides [135]. In liquid
appropriate counterion or stocked in SO2 , the products of the oxidation of
the solution for several weeks. This t-Bu2 S2 react with phenol yielding S8
reagent regioselectively reacts with and 4-t-butyl phenol almost quantita-
various strongly to weakly activated tively [136].
arenes to afford their methylthiation in The molecule of a thiol or a disulfide
good to excellent yields (Eq. 21) [134]. can serve as a nucleophile for RS+ cations.
Thus, anthracene and 2,6-dimethylphenol Thus the reaction of sulfenium cations,
electrogenerated in CH2 Cl2 /Bu4 NClO4 ,
give 9-methylthioanthracene and 6-
with these substrates results in unsym-
methylthio-2,6-dimethylphenol in 78%
metrical diorganyldisulfides in 47 to 90%
and 97% isolated yields, respectively.
yields (Eq. 22) [137].
Polymethylthiation was also observed
and, with thiophene as a substrate, the −2e R′SH (R2′S2)
R2S2 2 RS+ RSSR′
bis-methylthiated product was formed
predominantly (Scheme 35). (22)
The oxidation of a mixture of aromatic
disulfides, Ph2 S2 or Tol2 S2 , with 2,2,2,-
−2e +
3 Me2S2 2 Me S S Me trifluoroethylamine affording arylsulfany-
SO2/Bu4NPF6 lation of the amino group was reported
Me S (Eq. 23) [138].
(MeS)3+ + ArH −3e

ArSMe CF3CH2NH2 CHF3CH N SAr
−H+, −Me2S2
ArSSAr, −3H+
(21) (23)
When both para- and ortho-positions
of the arene are available for substitu- 9.2.6
tion, a mixture of ca. 9 : 1 p- and o- Tetrathiofulvalenes
methylthioproducts was obtained.
It is interesting that dialkyldisulfides Electrooxidation of tetraorganylthioethy-
(Alk = t-Bu) usually cleave on the S−S lenes (13) (R = Me, Et, Ph) [139–142]
bond to produce corresponding sulfe- and bicyclic tetrathiofulvalenes (14) [143]
nium cations, whereas di-t-butyldisulfide occurs in two reversible one-electron steps
undergoes the S−C bond cleavage [135]. (Scheme 36).
SMe SMe
(MeS)3+
+ +
MeS SMe SMe MeS SMe
S S S S
a, a : a, b = 10 : 1
Scheme 35 Bismethylthiation of thiophene.

RS SR R1 S S R4
RS SR R2 S S R3
(13) (14)
S S −e S S
+ •
S S Ep = 0.68 V vs SCE S S
S S −e S S
+ • + +
Ep = 1.12 V S S
S S
Scheme 36 Reversible 1e-oxidations of tetrathiofulvalenes.
Authors [143] suppose that sulfur atoms with a gap between the potentials of
are not affected by oxidation and only act formation of a cation radical and of a
as activating double bond substituents. dication of about 0.27–0.46 V depending
However, the analysis of the electronic on the nature of the substituents at S
structure of tetrathiofulvalene shows that, atoms. Similarly, crown ether derivatives
resulting from the interaction of π(CC) of tetrathiofulvalene (15) undergo two con-
secutive reversible oxidations (E1/21 = 0.48
and π(S) orbitals, HOMO of this molecule
is an antibonding combination of π and E1/2 = 0.64 V vs SCE [152]), the po-
2
and nπ orbitals with the predominant tential of the first of which shifts anodically
contribution being from the latter. Indeed, in the presence of several ions (Li+ , Na+ ,
the substitution of one or more S atoms K+ , Ag+ ) in solution.
with Se results in a less conjugated system
and, as a consequence, in higher oxidation S S
S S
potentials [144].
Other conditions being equal, the first O O
oxidation potentials of tetrathiofulvalenes S S S S

1–5 1–5
are usually less positive than those of (15)
tetrathioethylenes [141–151]. The first re-
versible oxidation of tetrathiofulvalenes The redox properties of bis-fused TTF
normally occurs at 0.2–0.8 V versus SCE, derivatives and unsymmetrical TTF deriva-
whereas the second occurs at 0.6–1.2 V tives (16) and (17) were reported [153, 154].
O S S S S O S S R
O S S S S O S S R
(16) (17)
S S S S
R R
S , S , S S
An extensive review on bis-tetrathioful- 1-methylpyrrole [167], polyethers possess-

valenes in which the TTF moieties are ing two 3-thienyl units [168], polythiophe-
separated by several spacers was recently nol [26], polymers of 3-thienyltrifluoroace-
published [155]. tamide and 3-thienylheptafluorobutyra-
mide [169], poly(4-R-2,2 -bithiophenes)
9.2.7 (R = Oct, CH2 OH, CO, CO2 Me) [170],
Sulfur-containing Polymers poly(3-butylthiophene-co-3-bromothioph-
ene) [171], disulfide-containing polymer of
Because of a remarkable n-π conjuga- 2,5-dimercapto-1,3,4-thiadiazole [27], poly-
tion in aromatic sulfides, and hence an (3,4,3 ,4 -tetraoctyl-[2,2 ]bithienyl) [172],
extended charge delocalization in their polymers produced by anodic coupling
p- or n-doped forms, sulfur-containing of a series of dipyrrolyl-ethylenes, -thio-
polymers have good potentialities for phenes, -phenylenes, and -diethylene-thio-
use in many fields dealing with conduc- phenes [173], poly p-nitrophenyl-function-
tive polymers. Such polymers are usually alized thiophenes [174], poly(2,5-bis(3,4-
obtained by anodic oxidation of corre- ethylenedioxy-2-thienyl)pyridine) exhibit-
sponding monomers and oligomers under ing multicolor electrochromism for neu-
low-nucleophilic conditions [156, 157]. Be- tral, p- and n-type doped forms [175], and
cause of the above-mentioned conjugation, many others.
the oxidation of the polymer is easier than
that of the starting material, so the poly-
mer formed is obtained in its doped form 9.3
as exemplified below for the polythiophene Reduction
formation (Scheme 37).
Thus, many polymers with dif- 9.3.1
ferent conductivity were synthesized. Thiones
To cite a few, these are poly-
thiophene [158], 3-methylthiophene [159], In general, it may be expected that thiocar-
polymers of 3-thiophene-acetic acid and bonyl compounds are easier to reduce ca-
methyl 3-thiophene-acetate [160], poly(2,5- thodically than the corresponding carbonyl
thienylenevinylene) [161], poly(benzo[b]- structures. There are a few examples deal-
thiophene) [162], poly(naphto[2,3-c]thio- ing with the cathodic reduction of thiones.
phene) [163], poly(dithieno[3,2-b;2 ,3 -d]- Let us quote the case of thiobenzophenone,
thiophene) [164], poly(3-n-hexylthiophene) which affords readily a rather stable radi-
[165], poly(2,5-di-(2-thienyl)-thiophene) cal anion at a potential that is +0.5 V more
[166], copolymers of thiophene and positive than that of benzophenone, when
m+
−2(n − 1)e −(mn)e, (mn)X−
n
S −2(n − 1)H+ S S
n mX− n
p-doped form
Scheme 37 Oxidation of thiophene to p-doped polythiophene.

9.3 Reduction 257
R R
R +e
S CH S Y + C(OMe) S Y
MeOH, Y−X, −X
R′
R′ R′
Y = Me, PhCH2, PhCO, Ac
Scheme 38 Cathodic alkylation of thiones.
reduced in dimethylformamide (Eq. 24). Electrochemical investigations of 3-

heterosubstituted 2-cyclohexene-1-thiones
Ph Ph of the general formulae (19) are available
• in a recent literature [183, 184].
C S + e− C S The cathodic coupling of 4H-pyran
Ph Ph 4-thiones (20) in nonaqueous media
(24) was achieved in good or even high
Such anion radicals derived from yields [185, 186] to afford π-donors like
bipyranylidenes.
thiones were shown to play the role of
To allow anion radicals generated from
nucleophiles as well as that of reducing
structure (20) to dimerize more rapidly,
agents towards alkyl halides [176–178], to-
this reaction was carried out in the
sylates [178], and acetylchloride [176]. This
presence of an electrophile. For exam-
way, thiobenzophenone could be cathodi-
ple, in the presence of EtBr as elec-
cally converted in the presence of benzyl
trophile, the cathodic coupling of struc-
chloride and benzoic anhydride to afford
ture (20) (X = O, R1 = R2 = Ph, R3 =
the corresponding products in good yields R4 = H) may be depicted as follows
(Scheme 38). (Scheme 39).
Similarly, aliphatic thiones are also read- Such a coupling reaction when achieved
ily reduced at microcathodes in DMF. in electrophilic media was shown to be of
Thus, thiocamphor exhibits a one-electron a general character. Thus, thiocoumarines
reversible step at −1.88 V versus SCE, could be also converted into corresponding
which is about 0.9 V more positive than π-donor dimers in one step and in good
the potential of the reduction of camphor yields.
under the same experimental conditions. The coupling of strongly activated
α,β-unsaturated thiones such as (18) were thiones (20) (X = S and NR), was
also investigated polarographically in pro- also achieved, however, in much lower
tic media. Similarly [179–182], reduction yields [187].
of α,β-ethylenic ketones and aldehydes in 1,2-Dithioles-3-thiones (21) were – and
acidic media yielded dimers. continue to be – frequently studied
S
MeS RR′N
R3 R4
S S
R1 X R2
Me Me Me Me
(18) (19) (20)
Ph Ph
−
e • Radical
O S O SEt
EtBr Dimerization
Ph Ph
Ph Ph Ph Ph
SEt EtSSEt
½ O O ½ O O
EtS
Ph Ph Ph Ph
Scheme 39 Cathodic dimerization with subsequent disulfide elimination of pyran-4-thiones.
[188–196] in electrochemistry. Thiourea and related compounds like

thioamides have been studied polaro-
S S graphically in alcoholic buffered me-
S R1 dia. Being cathodically reduced, benzotri-
R2 azepine (22) undergoes a ring contraction
(21) affording the corresponding quinazoline
(23) (Eq. 25) [194, 195].
Many papers deal with both analytical
determination and cathodic transforma- H S H
N N S
tions of thiones (21). Thus, a four-electron 2e−
NH
reduction of OLTIPRAZR [4-methyl-5-(2- NR1
NH
pyrazinyl)-1,2-dithiole-3-thione] produces Ph R2 Ph
several species that could account for
the schistosomicidal activity of metabo- (22) (23)
lites of the starting compound. The first (25)
two-electron reduction (in aqueous media) Lastly, the electrochemical reduction of
affords the scission of the S−S linkage 3-imidazolin-5-thiones in an AN solution
and the thus formed dianion can be read- showed a rather unexpected migration
ily [197] alkylated by common alkyl halides. of the aryl group from nitrogen to sul-
Let us note that the cathodic behavior of fur [196] occurring under electron transfer,
structure (21) was shown to be strongly in- although the mechanism was not strictly
fluenced by the nature of substituents and proven by the authors (Scheme 40).
particularly [198] by the electron-donating Thioesters and dithioesters are readily
ability of R1 . reduced at a mercury cathode. In the
e−
S N M+X− S• N S N
acetonitrile
Hg cathode
M+
C C C
O Ph O Ph Ph O
Scheme 40 Reductive 1,3-benzoyl migration.

9.3 Reduction 259
presence of electrophiles [199–201] (e.g. conditions, tetraorganyldiphosphine disul-

primary alkyl halides, dimethylsulfate), fides, RR P(S)-P(S)RR (R, R = Ph, Bz,
corresponding alkylated compounds can Me, Et, Pr, i-Pr, Bu), undergo the elec-
be formed (Scheme 41). troreduction within the interval of poten-
Benzenecarbodithioesters and carbo- tials from −1.54 to −2.48 V versus the
thio-S-esters were shown to yield Hg pool [197]. The process is supposed
diphenylacetylene by the cathodic to occur with the two-electron reductive
reduction in aprotic media. Thus, cleavage of one of the bonds formed
the formation of diphenylacetylene by sulfur.
involves [202] two molecules of a substrate.
The cathodic reactivity of thioamides 9.3.2
involving a similar alkylation of the C=S Sulfides
group in the presence of primary alkyl
halides was reviewed [199–201]. Dialkyl sulfides RSR are known [205] to
One-electron reversible reduction of be electrochemically inactive in all cath-
triarylphosphine sulfides in DMF/Et4 NI ode materials and solvents considered.
leads to an anion radical [198, 203, 204]. On the contrary, arylalkylsulfides ArSR
The second step of the reduction, occur- and diarylsulfides ArSAr , in general, can
ring at slightly more negative potentials, exhibit [206] an irreversible two-electron
results in different products of cleavage of cathodic step at fairly negative potentials.
P−S or P−C bonds – triphenylphosphine, As a matter of fact, diphenylsulfide was re-
benzene, and diphenylthiophosphinic acid ported to be polarographically reduced in
(Scheme 42). DMF at a potential of E1/2 = −2.549 V ver-
Tetraorganyldiphosphine sulfides, R2 sus the Ag+ /Ag electrode. Phenyl methyl
P(S)-PR2 (R = Ph, Me) can be reduced sulfide was found to be even more difficult
in DMF/Et4 NI at about −1.8 V ver- to reduce under the same experimental
sus the Hg pool [197]. The process conditions: a wave at E1/2 = −2.751 V was
is supposed to occur with the two- observed. Such negative potentials pre-
electron reductive cleavage of one of the clude the use of hydroorganic solvents
bonds formed by sulfur. Under similar and platinum electrodes. The assumed
S SMe
2e, H+, Me2SO4
C C H
SBut SBut
Scheme 41 Reduction of dithioester.
+e −•
Ar3P S Ar3P S
Ar Ph, PhCH CH
−•
Ph2P S− + Ph− (PhH)
+e
Ph3P S
Ph3P + S2−
Scheme 42 Reduction of triarylphosphine sulfides.

e− − kc
•
ArSR ArSR • ArS− + R
Cleavage
− Fast
R• + ArSR • R− + ArSR
R− + Proton source RH
Scheme 43 Reductive cleavage of arylsulfides.
mechanism would correspond to a Disp reinforced the stability of the primary an-
scheme as shown above (Scheme 43). ion radical while the cleavage rate (PhS−
To date, few quantitative studies are was proven to be the leaving group)
available on sulfides. However, the rates decreased (kc ≤ 1 s−1 ). Transient arylsul-
kc are probably very high when weakly fonyl σ radicals of structure (25) were
activated ArSR are considered. shown to act as electrophiles [208] and
SPh therefore used as intermediates in SRN 1 re-
PhS SO2R actions when electro-inactive nucleophiles
SPh were added to the electrolysis solution.
The reduction of sulfides bearing a
(24) (25)
vic-OH group involves a fast cleavage
With 1,2-di(phenylthio)benzene (24), of the C−S bond accompanied by a
two successive two-electron steps [207] simultaneous elimination of the hydroxyl
can be observed in aprotic DMF (E1 = group. This process can be efficiently used
−1.82 V and E2 = −2.11 V vs Ag/AgI as a mild method to create double bonds,
0.1 M /I− reference system). On the other for example, from ketones [209–211]. The
hand, substitution by efficient electron- yields of such a process are fairly high
withdrawing groups might change dramat- (Scheme 44).
ically the cathodic behavior of ArSR-type The reduction of α-carbonyl diphenyldi-
compounds. Apparently, the captodative thioacetals [212] was reported to be self-
character of substituents attached to the catalyzed (with formation in the course
phenyl ring (see Structure 25) strongly of the cathode process of the couple
R1 R1 R1
PhSCH2Li 2e−
C O C CH2SPh C CH2
1) SPh−
2) OH−
R2 R2 OH R2
Scheme 44 Cathodic elimination of vic-hydroxy-arylsulfides.
O R2 O R2
2e−
R1 C C SPh R1 C CH SPh
PhS−, H+
SPh
Scheme 45 Cathodic cleavage of a α-carbonyl arylsulfide.

9.3 Reduction 261
PhS-SPh/PhS− that acts as a redox cat- phenylthiolate onto the mercury electrode.
alyst at the potential of −0.63 V vs NHE) With R = t-Bu, the bulkiness of the thio-
(Scheme 45). late forbids that and the cleavage reaction
Hexathioalkyl-substituted benzenes are could be evidenced (by the detection of
considered as new π-acceptors [213]. an anion radical of very short lifetime)
(Scheme 46).
SR The electroreduction of benzothiophene
RS SR presents an example when the saturation
of a double bond can compete with the
RS SR S−C bond cleavage and the chemoselectiv-
SR ity depends on the experimental conditions
(26) (Scheme 47) [214].
Unlike oxygen derivatives, thioesters of
Structures such as (26) were demon- phosphor(III) acids (S-ethyldiphenylphos-
strated [103] to be fairly easily reduced at phinite, S,S-diethylphenylphosphonite and
a Pt electrode. Thus, when R = Ph, an an- triethylthiophosphite) undergo electrore-
ion radical (E ◦ = −1.26 V vs Ag/AgI/I− duction at DME (dropping mercury elec-
0.1 M) of high stability is formed. How- trode) in DMF or AN [215]. An irreversible
ever, macroelectrolyses of the compounds two-electron process results in the P−S
(26) could not be achieved at all since bond scission.
whatever the amount of electricity passed p-Diphenylarylsulfophosphamides ex-
through the cell, the starting material was hibit facile cathodic cleavage reaction yield-
totally recovered. The compounds (26) are ing, after quenching, diphenylphosphinic
expected to react slowly with the tetraalky- acid and aryl sulfide [216].
lammonium salt R4 N+ and the reaction
would correspond to an indirect reduc- 9.3.3
tion of the electrolyte. Compounds (26), Disulfides
with R = primary alkyl groups, led – even
in DMF – to strong self-inhibition ex- The reduction of disulfides is a reverse re-
plained by the adsorption of produced action of thiol oxidation and, under protic
SBut SBut
t-Bus SBut t-Bus SBut
+ − + t-Bu•
e
t-Bus SBut t-Bus SBut
SBut S
Scheme 46 Cathodic cleavage of hexa(thio-t butyl)benzene.
Wet THF/Bu 4NBF4

+2e S
S C2H5
H2O/Bu4NOH
SH
Scheme 47 Two pathways for the reduction of benzothiophene.

conditions, many reactions discussed in takes place along with the homogeneous
Sect. 9.2.2 can be effected in the back reduction of the disulfide (Scheme 49).
direction. Since the process involves a Diaryldisulfides can as well act as elec-
thiolate-anions formation, it can be used trophiles toward electrogenerated nucle-
for in situ generation of S-nucleophiles re- ophiles [221].
acting with appropriate electrophilic part-
ners to give alkylated or acetylated products 9.3.4
(Eq. 26) [217]. Sulfoxides
+2e 2 EX Since diorganyl sulfides and sulfoxides can

RSSR 2 RS− 2 RSE
2X− be mutually interconverted electrochemi-
(26) cally [222] (for the oxidation of sulfides
The electroreduction of disulfides R2 S2 to sulfoxides and further to sulfones, see
(R = Ar, Alk), in the presence of car- Sect. 9.2.3), sulfoxides take an intermedi-
bonyl compounds and Me3 SiCl, includes ate position between sulfides and sulfones
the formation of intermediate thiosilanes (Eq. 27).
and results in trimethylsilyl ethers of
hemithioacetals of ketones and aldehydes R R
Oxidation
or in full thioacetals depending on whether S S O (27)
Reduction
a two-compartment (a) or an undivided (b) R R
cell was used (Scheme 48) [218].
The above process carried out with- Chemical reduction of sulfoxides can be
out a carbonyl compound is probably the carried out in aprotic solvents according
best means to smoothly obtain thiosi- to several routes. It formally deals with an
lanes [219]. exchange of oxygen atoms using trivalent
Upon activation of disulfides (R = Bz, derivatives of phosphorus (PI3 , PCl3 ),
Pr, t-Bu) by electrogenerated anion rad- boron (BBr3 ) as well as derivatives of
icals of some activated olefins [220] the silicon (MeSiCl3 ). Other methods consist
formation of a saturated thioalkyl product in the use of reducing reagents in the
a SR
O OSiMe3
+2e
RSSR RSSiMe3
Me3SiCl
b SR
SR
Scheme 48 Hemithioacetals and thioacetals via reduction of disulfides in the presence of ketone.
O O
e, Pr2S2
OMe OMe
SPr
Scheme 49 Reductive thioalkylation of methyl cinnamate with disulfide.

9.3 Reduction 263
presence of Lewis acids (like NaBH4 + a disproportionation induced by electron

TiCl4 ). transfer) (Scheme 50).
Electrochemically, the reduction of acti- α,β-Ethylenic sulfoxides were shown
vated sulfoxides (unsaturated or aromatic) to behave similarly. However, cleavage
in protic media exhibits a specific step lead- reactions (partial formation of sulfonate
ing to corresponding sulfides. However, ion) as well as a coupling reaction (the
in acidic solutions of sulfoxides a hydro- behavior similar to that of α,β-ethylenic
gen reduction wave can be seen [223, 224] ketones) could clearly be demonstrated
because of the reduction of their pro- (Scheme 51) [226].
tonated form. On the contrary, in the
absence of electrophiles (in aprotic DMF), 9.3.5
the reduction of aromatic sulfoxides was Sulfones
reported to afford [225] a complex between
the reduced form and the substrate (the Most sulfones are known to react
process therefore would be analogous to with chemical reagents (dissolved metals,
Ar1
Ar1 Ar1 Ar1
− Substrate
e •
S O S O− S• O S O−
Ar2 Ar2 Ar2 Ar2
−
2
Ar1 Ar1 O
e− + S Arylsulfinate(s) as
S
cleavage product(s)
Ar2 O
Ar2
Scheme 50 Disproportionation of sulfoxide by electron transfer.
e− •
Ar SO CH CHR Ar SO CH CHR
High concentration (coupling)
• ArSO CH2 C R
ArSO CH CHR
•
ArSO CH CHR ArSO CH2 C R
R
2 ArSO +
R
Low concentration
H+/e−
Ar SO CH2 CHR ArSO + RCH CH2
Scheme 51 Cathodic cleavage and coupling competing in reduction of α,β-ethylenic sulfoxides.

amalgams) via electron transfer. Such re- of aromatic sulfones is depicted in the
actions can be successfully mimicked by Scheme 52 below:
using electrochemistry with cathodes (Hg, The above mechanism underlines the
Pt, glassy carbon) whose potentials can sulfone anion radical as an obliga-
be adjusted to fit the level of the LUMO tory intermediate. The lifetime of such
of a considered sulfone. Generally speak- species depends on the nature of sub-
ing, phenyl alkyl sulfones PhSO2 R (taken stituent(s) on the Ar group. Thus, with a
as model molecules) are electroactive (with strongly electron-withdrawing substituent
the standard potential E ◦ in the range from in position 4 or/and 2 (like NO2 and
−2.2 V to −2.4 V vs SCE) while dialkyl CN groups), highly stable free rad-
sulfones are not sufficiently activated to ex- icals can be obtained [229, 230]. Note
hibit any felt electron transfer up to −3.0 V also that two cleavage routes (a) or/and
versus SCE. Since phenyl alkyl sulfones (b) can be observed according to the
are weakly electroactive [227, 228], electro- nature of Ar and R and the posi-
chemical steps are only visible in aprotic tion of substituents on the aromatic
organic solvents. The reductive cleavage ring [231, 232].
e−
ArSO2R [ArSO2R]−•
a
ArSO2− + R•
[ArSO2R] −•
b
RSO2− + Ar •
Ar • / R• + [ArSO2R]−• Ar− / R− + ArSO2R

Proton source
Ar− / R− ArH / RH
or
H• transfer
Ar • / R• ArH / RH
From solvent
Scheme 52 Sulfone anion radical in the reductive cleavage of arylsulfones.
SO2R SO2R
SO2R
SO2R RO2S SO2R

SO2R
(27) (28) (29)
SO2R
RO2S SO2R RO2S SO2R
RO2S SO2R RO2S SO2R

SO2R
(30) (31)
9.3 Reduction 265
Thus (29) and (30) at the level of Other disulfones like (32) and (33) were
the first one-electron transfer will lead studied (see Ref. [6]). They exhibit surpris-
to dimers [233] while cleavage reactions ingly stable anion radicals (and even a
will occur only after the disproportion- stable dianion with (32)). Such charged
ation or an electrolyses at the level of species could be used as redox mediators.
the second electron-transfer step [6] (pro- However, reduction of alkyl halides RX by
ducing a dianion). Bulky hexasulfones (33) did not permit the formation of alky-
(31) with different R (Alk, Ar) undergo lated products presumably because of the
a conformational change through elec- strong steric strain induced by alkylation
tron transfer [234]. Separate redox systems of the corresponding carbon atoms in the
were clearly evidenced for a sterically con- cyclobutene ring.
gested structure (presumably possessing a
chair form) of low E ◦ and for an unstable O O
SO2Ph
S
one (produced by electron transfer and of
a short lifetime) with a much higher E ◦
S SO2Ph
since it is more conjugated. Lastly, disul- O O
fones (27) and (28) appear to be cleaved.
(32) (33)
Both undergo an ipso substitution with for-
mation of an R• radical and a subsequent α,β-Ethylenic sulfones exhibit a behavior
coupling with the substrate anion radi- that could be considered as specific and
cal [235]. Sterical hindrance in (27) makes totally different from that of α,β-ethylenic
ortho-coupling unfavorable. However, the ketones or nitriles. Thus, with the present
disulfone (27) shows an interesting case of series, there is practically no case of
a reversible cleavage according to route (a) dimerization or double-bond saturation.
(see general reduction Scheme 52 of aro- This seems to be because of the fact
matic sulfones) and a reorganization of the that reduction of compounds of this
substrate, which can cleave to a phenoxy series cannot be completed neither in
derivative (Scheme 53) [236]. acidic nor in aqueous solutions because
Thus, the progressive accumulation of a fast cleavage occurs at the level of the
alkyl and/or arylsulfonyl groups onto a anion radical.
benzene ring (in the aromatic polysulfones Consequently, the reaction given below
(27)–(31)) led to an increasing stabiliza- could be regarded as an exception (reduc-
tion of the corresponding anion radicals. tion in a DMF/LiClO4 system). Aromatic
e−
28 RO2S −• SO2R RSO2 + • SO2R
Cleavage
•
RSO + O SO2R R S O −• SO2R
•
R + SO
Scheme 53 Reversible cleavage and reorganization of disulfone.

Ar1 SO2 CH2 CH Ar2

Aprotic DMF
2 Ar1SO2CH CHAr2
LiClO4/Hg or Ar1 SO2 CH2 CH Ar2
Pt anode
(34) 75%
Scheme 54 Cathodic coupling of α,β-ethylenic sulfone.
ethylenic sulfones (34) were found [237] like superoxide or acridine anion radical)
to lead selectively to the corresponding (Eq. 29). The product (36), unknown until
δ-disulfones with a high ratio of the d,l now, could be efficiently used in Diels-
isomer (d,l/meso >10) (Scheme 54). Alder synthesis.
Such a behavior, however, was not found It was checked to undergo the ca-
with vinyl arylsulfones: studies in aprotic thodic cyclodimerization, thus providing
organic solvents revealed the existence of a route [241] to ladderanes (37) (Eq. 29).
electrocatalytic cyclodimerizations. Thus, However, this process could not be gen-
sulfones ArSO2 CH=CHR afford corre- eralized by transfer to other unsaturated
sponding cyclodimers [238], often, almost sulfones, because the double bond can
quantitatively (in constant current elec- readily migrate to the β,γ -position, where
trolyses in DMSO/LiClO4 solution, the it favors the cleavage of the concerned
catalytic amount of electricity does not anion radical.
exceed 0.1 F mol−1 ) (Eq. 28). SO2Ph
EGB
SO2Ph 35
Cathode Pt
2 PhSO2 (a) (36)
Activation by (29)
electron transfer SO2Ph Cathode
36
(35)
Trans isomer PhSO2 O2SPh
(b) (37)
(28)
Cyclobutane (35) and its analogs were Lastly, the anodic oxidation of sulfone
not described in literature so far. They anions could be achieved. Examples of the
can be regarded as an easy source both dimer formation are available in a recent
of a cyclobutyl radical [239] (by cleavage of paper [242]. The activity of α-sulfonyl
C−S bond under electron transfer) and a anions at a positively polarized electrode
dienophile [240]. Thus, (35) readily yields was pointed out. The coupling of α,α-
the corresponding cyclobutene (36) in the bissulfonyl anions by anodic oxidation was
presence of electrogenerated bases (EGB) also achieved. These coupling reactions
B(−) −
RSO2CH2SO2R RSO2CHSO2R
BH
−e− • RSO2 CH SO2R

RSO2CHSO2R ½
∆ RSO2 CH SO2R
Scheme 55 Anodic coupling of α,α-bisulfonyl anions.

9.3 Reduction 267
were found to be reversible (with reverse leading to their formation, the mech-
formation of the free radical upon the anism of the heterogeneous (direct)
temperature increase) (Scheme 55). reduction is strongly expected to be
ECE (two heterogeneous electron trans-
9.3.6 fers E associated with an extremely
Sulfonium Salts fast chemical reaction C). To illustrate
the influence of the nature of sub-
The cathodic scission of onium cations stituents R on the ease of the elec-
such as ammonium, phosphonium, sul- troreduction in the series of organyl(1-
foxonium, and sulfonium salts was exten- naphthyl)methyl sulfonium salts (39),
sively studied with regard to their reactions some reduction potentials are collected in
and applications in organic synthesis. All Table 1.
sulfonium ions, whatever their structure,
exhibit a cathodic step. Some of them are
easily reduced in aqueous media. Their
fairly good solubility (both in aqueous and S+ X−
organic media) allows them to be regarded Me R
as electrolytes as well and their cathodic (39)
reactivity eventually influences product
distribution. The first charge transfer to Tab. 1 Potentials of reduction (Ep , vs SCE) of
a salt of type (38) could be understood as sulfonium salts (39) at a Pt microelectrode in
a fragmentation reaction to free radicals AN/Bu4 NBF4 ; C = 10−3 M (from
Ref. [243–246].)
either at the cathode surface or in the bulk
of the solution (by homogeneous redox
R X Ep (V)
catalysis) (Scheme 56).
In the presence of an excess of re- −CH3 CF3 SO3 −1.51
ducing species, free radicals (R1 )• , (R2 )• −CH(CH3 )2 BF4 −1.49
or/and (R3 )• are usually reduced very fast −CH2 -C6 H5 BF4 −1.23
and owing to the probable dissociative −CH2 COC6 H5 CF3 SO3 −0.74
−CH2 C(C6 H5 )=C(CN)2 CF3 SO3 −0.17
character of the relevant electron transfer
•
(R1) + R2SR3
+ e− • •
R1R2R3SR− R1R2R3S (R2) + R1SR3
−X− •
(R3) + R1SR2
(38)
Scheme 56 Cathodic cleavage of sulfonium salts.
O
S+ S+ S+
−
Me CH2Ph Me CH2Ph Me CHPh
−0.79 V −1.23 V −1.74 V
Lastly, let us emphasize the large to an overall two-electron process

difference of reducibility (Ep vs SCE) (Scheme 57).
between sulfoxonium, sulfonium, and its Reduction potentials are much too
corresponding ylide. cathodic to allow reaction in aqueous
The nature of the cleavage and the solvents. This reaction is efficient for
possible stability of sulfuranyl radicals the deprotection of the amine function.
formed after electron transfer could be It is then particularly well adapted to
advantageously revealed by ESR and the achieve the deprotection in a very mild
associated technique of spin trapping and selective manner [249], and to allow
as well [247, 248]. Spin traps such as the synthesis of macrocycles in high yield
t-butylphenylnitrone and nitrosodurene (Scheme 58) [250]. Note that mesitylates
could contribute to demonstrate the struc- are not electrochemically active.
ture of the leaving radical formed by
cathodic decomposition of the sulfo-
nium substrate. 9.4
Sacrificial Sulfur Electrodes
9.3.7
Sulfonamides and Deprotection to Amines Although it does not deal with the direct
redox processes of sulfur organic com-
In nonaqueous media, the cathodic pounds, the use of sacrificial electrodes,
cleavage of N−S bonds occurs according both cathodes and anodes producing
−•
R1 R1 R1
e− •
N SO2Ar N SO2Ar N + ArSO2−
R2 R2 R2 R1
e−, H+
NH
R2
Scheme 57 Cathodic cleavage of sulfonamide for deprotection of amines.
Ts
H
N (CH2)n N (CH2)n
8e−
Ts N N Ts HN NH
−4Ts−, 4H+
(CH2)n N (CH2)n N
H
Ts
Ts = CH3 SO2
n = 1:yield = 96%
n = 2:yield = 95%
Scheme 58 Cathodic deprotection of macrocyclic polyamines.

9.4 Sacrificial Sulfur Electrodes 269
under polarization Sx 2− or Sy 2+ species, yield of tetrasulfides is observed owing

turned out to be a very convenient elec- to the formation of the less oxidized
trochemical way to obtain various organo- form S2 2+ . α,ω-Terminal dithiols, used
sulfur products. Usually made of a molten in this process, give cyclic products. A
mixture of elemental sulfur and a carbon cyclic sulfide, 2-[1,3]-benzothiadiazole, was
powder, these electrodes behave like con- obtained when using o-phenylenediamine
ventional inert electrodes in the range of in a similar process [252]. With aniline, one
potentials between −0.6 and 1.6 V vs. SCE; obtains the ortho-substituted product, 2,2 -
at these potentials, sulfur is not involved diaminodiphenylsulfide. It is interesting
in the formation of products. At potentials that when a secondary or a tertiary
below −0.6 V or above 1.6 V, the reduction aromatic amine is taken, the formation of
or oxidation of sulfur takes place, respec- a para-substituted diarylsulfide takes place
tively. The cathodic dissolution of the exclusively.
sulfur electrode produces S3 −• , S4 2 , and Another point worth mentioning is
the selectivity of the electrogenerated
S8 2− species, whereas its anodic process
electrophilic sulfur species toward aro-
mainly generates S2+ cations. When us-
matic substrates in the reaction with
ing sacrificial sulfur electrodes, a general
diphenylether and diphenylamine. In the
rule applies: the higher the corresponding
first case, an internal ortho-cyclization
potential (cathodic or anodic), the more
yields in phenoxathiin, in the second, a
reduced/oxidized (and hence containing
para-substitution occurs [252] giving a lin-
less S atoms) S-species are produced, for
ear product (Scheme 59).
example, S4 2− > (S6 2− ↔ 2S3 −• ) > S8 2−
More activated substrates such as
in the cathodic and S2+ > S2 2+ in the thiophene, produce a mixture of α,α -
anodic process. dithiophene mono-, di-, tri-, tetra-, and
polysulfides. When both α-positions of
9.4.1 thiophene are taken by methyl groups,
Sacrificial Anodes a β,β - and a fused tricyclic product
were obtained.
Diorganyltrisulfides (RS3 R, R = Alk, Ar)
can be obtained by the reaction of 9.4.2
electrogenerated S2+ cations with thiols Sacrificial Cathodes
in good synthetic yields [251]. When the
potential of the electrolysis shifts to higher Cathodic generation of Sx 2− species
potentials (2.3 V vs SCE), trisulfides are in the presence of alkylhalogenides
preferentially formed; as the potential provides polysulfides Alk-Sx -Alk (x =
is set at about 1.8 V, a rise of the 2, 3, 4). At more negative potentials
O
X=O
X S
+ S2+
H H
X = NH
N S N
Scheme 59 Anodic substitution of aromatic compounds with electrogenerated S2+ .

(−1.5 V vs SCE) one obtains equal quan- of about 22% [259]. Cumulene deriva-
tities of di-, tri-, and tetrasulfides, at tives such as 1,1-di-p-chlorophenylbuta-
less negative potentials (−0.9 V), tri- 1,2,3-triene, 1,1-di-p-chlorophenyl-4,4-di-
and tetrasulfides are obtained almost p-methylphenylbuta-1,2,3-triene, and
exclusively [253]. Substituted monohalo- 1,1,4,4-tetraphenylbuta-1,2,3-triene produ-
benzenes such as 4-bromobenzophenone ced 7-membered pentathiepins with 5
and 2-chloronitrobenzene give corre- sulfur atoms [260].
sponding diaryldisulfides [254–256]. The Activated unsaturated compounds react
addition of MeI in the last case, re- with Sx 2− species as well [261]. Thus, acry-
sulting in methyl-(2-nitrophenyl)disulfide, lonitrile gives bis(2-cyanoethyl)trisulfide as
allowed to suppose the process to occur a main product along with some amount
via an intermediate 2-nitrophenyl disul- of 6-amino-5-cyano-7,8-dihydro-4H -1,2,3-
fide anion. trithiocine, if the reaction was carried out
1,4- and 1,2-dinitrobenzene react with in strong basic media (Scheme 60).
polysulfide ions (S3 .− ↔ S6 2− ) or aryl- When 3-chloro-3-phenyl acrylonitrile
disulfide anions ArS2 2− , obtained by was involved in this reaction, a bi-
adding sulfur to the solution of electrogen- cyclic product, 6,6 -diphenyl-4,4 -bis(1,2,3-
erated 4-methylphenyl or 4-fluorophenyl dithiazine) was formed in good yield [262].
thiolates, affording the products of nu- Five-membered cyclic disulfides were ob-
cleophilic aromatic substitution of ortho tained in this reaction when ethylenic
or para nitro groups – nitroarylthiolate, ni- esters or ketones were taken as an un-
troaryl disulfide ions, or an equilibrium saturated substrate (Scheme 61) [263].
mixture of nitroaryl mono- and disulfide An example of the formation of a
ions [257] or NO2 C6 H4 S2 Ar [258], respec- cyclic product, containing only one sul-
tively. fur atom, is the reaction of Sx 2−
In an SRN 1 process with polysul- anions with activated double bonds
fide anions, 3-bromoquinoline afforded of 1,5-diphenyl-1,4-pentadiene-3-one yield-
a mixture of diquinolinyl mono-, di- ing in a substituted oxotetrahydrothiopy-
and trisulfide, all in similar yields ran (Scheme 62) [253].
2 H2C CH CN + S32− NC (CH2)2 S3 (CH2)2 CN
Scheme 60 Michael addition with electrogenerated S3 2− .
Ph
+Sx2−
PhCH CHCO2Me
−HSx − 2−, −MeO− S
S O
Scheme 61 Cyclic disulfides by reaction of Sx 2− with methyl cinnamate.
(PhCH CH)2CO + Sx2−

Ph S Ph
Scheme 62 Double Michael addition of electrogenerated Sx 2− to a divinylketone.

Ph
C CHC(O)Ph
EtOH-DMF/Mg(ClO4)2 S2
C CHC(O)Ph
Ph
+Sx2−
PhCH CHC(O)Ph
Ph(O)C Ph Ph(O)C C(O)Ph
+
DMF/NaClO4
Ph S C(O)Ph Ph S Ph
(2 : 1)
Scheme 63 Michael addition of Sx 2− to benzalacetophenone.
A similar process with benzalace- The triple bond of the cyano group
tophenone results in different products, in benzonitrile is also affected by Sx 2−
the chemoselectivity being controlled by anions; thiobenzamide was formed in
the experimental conditions, namely the this case in a 40% yield [255, 256].
solvent and the supporting electrolyte An interesting example of a simul-
used [261]. Either an acyclic disulfide, taneous introduction of both sulfur
bis(2-benzoyl-1-phenylvinyl) disulfide (in and carbon using a sacrificial car-
EtOH-DMF/Mg(ClO4 )2 ), or two isomeric bon–sulfur cathode is the formation of 4-
thiophenes (in DMF/NaClO4 ) can thus be morpholino-α-thioxoethaneditioate from
obtained (Scheme 63). Upon the substitu- morpholine [264].
tion of a vinylic proton at C(2) with Br,
the reaction becomes more regioselective References
and the only product now formed is an
α,α -dibenzoyl thiophene derivative. 1. J. Q. Chambers in Encyclopedia of Electro-
The reaction of R1 −C≡C−R2 with the chemistry of the Elements (Eds.: A. J. Bard,
electrogenerated Sx 2− ions provides a H. Lund), Marcel Dekker, New York, 1978,
convenient method for the synthesis of p. 329.
2. O. Hammerich, V. D. Parker, Sulfur Rep.
substituted thiophenes (Eq. 30) [263]. Be- 1981, 1, 317.
sides thiophenes, some dithiols, divinyl- 3. B. Svensmark in Organic Electrochemistry
sulfides and 2,4,6-tricarboxyethyl-1,3,5- (Eds.: M. Baizer, H. Lund), Marcel Dekker,
trithiophenol were formed, the product New York, 1983, pp. 519–530.
distribution being governed by the na- 4. A. P. Tomilov, Y. M. Kargin, I. N. Chernikh,
Electrochemistry of Organoelement Com-
ture of the substituents in the starting
pounds, Nauka, Moscow, 1986, Vol. 2.
acetylenic substrate. 5. B. Svensmark, O. Hammerich in Organic
Electrochemistry (Eds.: M. Baizer, H. Lund),
R2 R2
Marcel Dekker, New York, 1991,
+Sx2−
R1 C C R2 pp. 659–700.
R1 S R1 6. J. Simonet in Supplement S. The Chemistry of
Sulfur Containing Functional Groups (Eds.:
10–85% S. Patai, Z. Rappoport), John Wiley & Sons,
(30) Chichester, 1993, pp. 475, 476.
7. H. Viertler, J. Gruber, V. Pardini in 31. M. Byloos, H. Almaznai, M. Morin, J. Phys.

Organic Electrochemistry (Eds.: H. Lund, Chem. B 1999, 103, 6554.
O. Hammerich), Marcel Dekker, New York, 32. M. Finot, M. McDermott, J. Electroanal.
2001. Chem. 2000, 488, 125.
8. P. L. Blankespoor, M. P. Doyle, D. M. 33. J. A. M. Sondaghuethorst, L. G. J. Fokkink,
Hedstrand et al., J. Am. Chem. Soc. 1981, Langmuir 1994, 10, 4380.
103, 7096. 34. C. M. Whelan, M. R. Smyth, C. J. Barnes, J.
9. C. T. Pedersen, V. D. Parker, Tetrahedron Electroanal. Chem. 1998, 441, 109.
Lett. 1972, 771. 35. Y. Sato, F. Mizutani, J. Electroanal. Chem.
10. K. Bechgaard, V. D. Parker, C. T. Pedersen, 1997, 438, 99.
J. Am. Chem. Soc. 1973, 95, 4373. 36. S. Q. Liu, Z. Y. Tang, A. L. Bo et al., J.
11. T. Matsuki, N. X. Hu, Y. Aso et al., Bull. Electroanal. Chem. 1998, 458, 87.
Chem. Soc. Jpn. 1988, 61, 2117. 37. D. Hobara, T. Sasaki, S. Mabayashi et al.,
12. E. V. Nikitin, A. C. Romakhin, V. G. Malaev, Langmuir 1999, 15, 5073.
Zh. Obshch. Khim. 1982, 52, 2358. 38. J. C. Yan, J. H. Li, W. Q. Chen et al., J.
13. E. V. Nikitin, A. C. Romakhin, V. G. Malaev, Chem. Soc., Faraday Trans. 1996, 92, 1001.
CA 1983, 98, 42 878. 39. S. Bharathi, V. Yegnaraman, G. P. Rao,
14. Y. G. Bydnikova, Y. A. Drozdova, V. V. Langmuir 1995, 11, 666.
Yanilkin et al., Russ. Chem. Bull. 1993, 42, 40. Z. Mekhalif, J. Delhalle, P. Lang et al.,
1069. Synth. Met. 1998, 96, 165.
15. Y. G. Bydnikova, Y. A. Drozdova, V. V. 41. F. Fichter, P. Sjostedt, Chem. Ber. 1910, 43,
Yanilkin et al., CA 1995, 122, 160 787. 3422.
16. W. Stricks, I. Kolthoff, J. Am. Chem. Soc. 42. C. F. Bennett, D. W. Goheen, U.S. Patent
85 418.224.
1952, 77, 5211.
43. C. F. Bennett, D. W. Goheen, CA 1968, 70,
17. R. S. Saxena, G. L. Khandelwal, J. Indian
N43434.
Chem. Soc. 1976, 63, 564.
44. J. Nishiguchi, H. Takumi, M. Toda et al.,
18. F. Said, D. Tuck, Inorg. Chim. Acta 1982, 59,
Nippon Kagaku Kaishi 1994, 1838.
1.
45. J. Nishiguchi, H. Takumi, M. Toda et al.,
19. F. Magno, G. Bontempelli, G. Piloni, J.
CA 1984, 102, 131623c.
Electroanal. Chem. 1971, 30, 375.
46. Jpn. Patent 82.126 982, Jpn. Kokai Tokkyo
20. R. S. Saxena, K. C. Gupta, J. Indian Chem. Koho.
Soc. 1970, 47, 101. 47. CA 1982, 97, 225686.
21. S. Leite, V. Pardini, H. Viertler, Synth. Com- 48. F. Magno, G. Bontempelli, J. Electroanal.
mun. 1990, 20, 393. Chem. 1972, 36, 389.
22. H. Berge, H. Millat, R. Strübing, Z. Chem. 49. V. Zhouikov, Zh. Obshch. Khim. 1998, 68,
1975, 15, 37. 1909.
23. G. Dryhurst, Electrochemistry of Biological 50. V. Zhouikov, CA 1999, 131, 242 932.
Molecules, Academic Press, New York, 1977, 51. H. Wendt, H. Hoffelner, Electrochim. Acta
p. 601. 1983, 28, 1453.
24. J. Antelo, F. Arce, F. Rey et al., Electrochim. 52. H. Wendt, H. Hoffelner, Electrochim. Acta
Acta 1985, 30, 927. 1983, 28, 1465.
25. J. K. Howie, J. J. Houts, D. T. Sawyer, J. 53. M. Elinson, J. Simonet, J. Electroanal. Chem.
Am. Chem. Soc. 1977, 99, 6323. 1993, 350, 117.
26. E. Tsuchida, H. Nishido, K. Yamamoto 54. V. Latypova, O. Yakovleva, V. Jouikov et al.,
et al., Macromolecules 1987, 20, 2316. Zh. Obshch. Khim. 1984, 54, 1085.
27. E. Shouji, D. A. Buttry, J. Phys. Chem. B 55. V. Latypova, O. Yakovleva, V. Jouikov et al.,
1998, 102, 1444. CA 1984, 101, 190 876.
28. T. Abe, S. Nagase, H. Baba, Bull. Chem. Soc. 56. S. Torii, I. Matsuyama, K. Kawasaki et al.,
Jpn. 1973, 46, 3845. Bull. Chem. Soc. Jpn. 1973, 46, 2912.
29. D. F. Yang, M. Morin, Can. J. Chem. 1997, 57. M. Elinson, J. Simonet, J. Electroanal. Chem.
75, 1680. 1992, 336, 363.
30. M. M. Walczak, C. A. Alves, B. D. Lamp 58. V. Latypova, V. Jouikov, G. Tchmutova et al.,
et al., J. Electroanal. Chem. 1995, 396, 103. Zh. Obshch. Khim. 1984, 54, 1551.
59. V. Latypova, V. Jouikov, G. Tchmutova et al., 86. M. Noel, V. Suryanarayanan, S. Chel-

CA 1984, 101, 170 472. lammal, J. Fluorine Chem. 1997, 83, 31.
60. M. Kimura, S. Matsubara, Y. Tamamoto 87. G. Le Guillanton, J. Simonet, Acta Chem.
et al., Tetrahedron 1991, 47, 867. Scand. 1983, B37, 437.
61. I. Tabakovic, I. Gaon, M. Distefano, Elec- 88. D. Andres, E. Laurent, B. Marquet et al.,
trochim. Acta 1998, 43, 1773. Tetrahedron 1995, 51, 2606.
62. M. Sugawara, K. Mori, J. I. Yoshida, Elec- 89. J. Nokami, S. Fukutake, H. Matsuura et al.,
trochim. Acta 1997, 42, 1995. Electrochim. Acta 1997, 42, 1993.
63. J. Yoshida, M. Sugawara, N. Kize, Tetrahe- 90. N. Furukawa, Bull. Chem. Soc. Jpn. 1997, 70,
dron Lett. 1996, 37, 3157. 2571.
64. S. Torii, H. Okumoto, H. Tanaka, Chem. 91. M. Cariou, T. Douadi, J. Simonet, New J.
Lett. 1980, 617. Chem. 1996, 20, 1031.
65. M. Kimura, S. Matsubara, Y. Sawaki et al., 92. T. Nogami, H. Tanaka, S. Ohnishi et al.,
Tetrahedron Lett. 1986, 27, 4177. Bull. Chem. Soc. Jpn. 1984, 57, 22.
66. M. Kimura, N. Saitoh, H. Kawai et al. in 93. Y. Matsumura, M. Yamada, N. Kise et al.,
Novel Trends in Electroorganic Synthesis (Ed.: Tetrahedron Lett. 1995, 51, 6411.
S. Torii), Springer, Tokyo, 1998, p. 73. 94. C. Liao, J. Chambers, I. Kapovits et al., J.
67. J. Nokami, M. Hatate, S. Wakabayashi et al., Chem. Soc., Chem. Commun. 1974, 149.
Tetrahedron Lett. 1980, 21, 2557. 95. W. Musker, T. Wolford, J. Am. Chem. Soc.
68. T. Fuchigami, H. Yano, A. Konno, J. Org. 1976, 98, 3055.
Chem. 1991, 56, 6731. 96. R. S. Glass, A. Petson, M. Hojjatie et al., J.
69. M. Kimura, K. Koie, S. Matsubara et al., J. Am. Chem. Soc. 1988, 110, 4772.
Chem. Soc., Chem. Commun. 1987, 122. 97. T. Tobien, H. Hungerbuhler, K. D. Asmus,
70. S. Furuta, T. Fuchigami, Electrochim. Acta Phosphorus Sulfur Silicon 1994, 95, 249.
1998, 43, 3153. 98. M. Watanabe, S. Suga, J. Yoshida, Bull.
71. S. Nakabayashi, K. Zama, K. Uosaki, J. Elec- Chem. Soc. Jpn. 2000, 73, 243.
trochem. Soc. 1996, 143, 2258. 99. J.-I. Yoshida, T. Maekawa, T. Murata et al.,
72. J. I. Yoshida, M. Itoh, S. Isoe, J. Chem. Soc., J. Am. Chem. Soc. 1990, 112, 1962.
Chem. Commun. 1993, 547. 100. R. S. Glass, Q. Guo, Y. Q. Liu, Tetrahedron
73. V. Jouikov, D. Fattakhova, Electrochim. Acta 1997, 53, 12 273.
1998, 43, 1811. 101. W. K. Musker, Acc. Chem. Res. 1980, 13,
74. J. I. Yoshida, S. Isoe, Chem. Lett. 1987, 631. 200.
75. T. Brigaud, E. Laurent, Tetrahedron Lett. 102. N. Nakayama, O. Takahashi, O. Kikuchi
1990, 31, 2287. et al., Heteroatom Chem. 2000, 11, 31.
76. A. Konno, T. Fuchigami, J. Org. Chem. 103. J. Simonet, University of Rennes, to be
1997, 62, 8579. published.
77. T. Fuchigami, A. Konno, J. Syn. Org. Chem. 104. K. Suda, J. Watanabe, T. Takanami, Tetra-
Jpn. 1997, 55, 301. hedron Lett. 1992, 33, 1355.
78. T. Fuchigami, M. Shimojo, A. Konno, J. 105. H. Cristau, B. Chabaud, H. Christol, J. Org.
Org. Chem. 1995, 60, 3459. Chem. 1984, 49, 2023.
79. P. Baroux, R. Tardivel, J. Simonet, J. Elec- 106. Q. N. Porter, J. H. Utley, J. Chem. Soc.,
trochem. Soc. 1997, 144, 841. Chem. Commun. 1978, 255.
80. S. Higashiya, T. Sato, T. Fuchigami, J. Flu- 107. J. Gourcy, P. Martigny, J. Simonet et al.,
orine Chem. 1998, 87, 203. Tetrahedron 1981, 37, 1502.
81. Y. K. Hou, S. Higashiya, T. Fuchigami, J. 108. M. Kimura, H. Kawai, Y. Sawaki, Elec-
Org. Chem. 1997, 62, 8773. trochim. Acta 1997, 42, 497.
82. Y. K. Hou, S. Higashiya, T. Fuchigami, J. 109. A. Martre, G. Mousset, R. Rhlid et al., Tetra-
Org. Chem. 1997, 62, 9173. hedron Lett. 1990, 31, 2599.
83. A. Konno, W. Naito, T. Fuchigami, Acta 110. P. Martigny, J. Simonet, J. Electroanal.
Chem. Scand. 1999, 53, 887. Chem. 1980, 111, 133.
84. T. Fuchigami, S. Higashiya, Y. K. Hou et al., 111. J.-G. Gourcy, P. Martinny, J. Simonet et al.,
Rev. Heteroatom Chem. 1999, 19, 67. Tetrahedron 1981, 57, 1495.
85. D. Andres, U. Dietrich, E. Laurent et al., 112. M. Platen, E. Steckhan, Chem. Ber. 1984,
Tetrahedron 1997, 53, 647. 117, 1679.
113. R. Glass, A. Petsom, G. Wilson et al., J. Org. 138. T. Fuchigami, S. Ichikawa, A. Konno, Chem.
Chem. 1986, 51, 4337. Lett. 1992, 2405.
114. M. Kimura, H. Kawai, Y. Sawaki in Novel 139. N. D. Canfield, J. Q. Chambers, D. L.
Trends in Electroorganic Synthesis (Ed.: Coffen, J. Electroanal. Chem. 1970, 24, 243.
S. Torii), Springer, Tokyo, 1998, p. 77. 140. M. Z. Aldoshina, R. N. Lubovskaya, M. L.
115. G. Bontempelli, F. Magno, G.-A. Khidekel, Synth. Met. 1980, 1, 379.
Mazzocchin, J. Electroanal. Chem. 1973, 42, 141. D. J. Sandman, T. J. Holnes, D. E. Warner,
57. J. Org. Chem. 1979, 44, 880.
116. V. Z. Latypova, V. V. Jouikov, Y. M. Kargin, 142. D. H. Geske, M. V. Merrit, J. Am. Chem.
Zh. Obshch. Khim. 1990, 60, 2759. Soc. 1969, 91, 692.
117. V. Z. Latypova, V. V. Jouikov, Y. M. Kargin, 143. D. L. Coffen, J. Q. Chambers, R. D.
CA 1991, 115, 7911. Williams et al., J. Am. Chem. Soc. 1971, 93,
118. G. Sanchez-Cano, V. Montiel, A. Aldaz, 2258.
Tetrahedron 1991, 47, 877. 144. R. D. McCullough, G. B. Kok, K. A. Lerstrup
119. J. G. Gourcy, G. Jeminet, J. Simonet, J. et al., J. Am. Chem. Soc. 1987, 109, 4115.
Chem. Soc., Chem. Commun. 1974, 634. 145. E. M. Engler, B. A. Scott, S. Etemad et al., J.
120. P. D. Machion, V. L. Pardini, H. Viertler, Am. Chem. Soc. 1977, 99, 5909.
Synth. Commun. 1990, 20, 365. 146. A. Charlton, M. Kalaji, P. Murphy et al.,
121. B. Dakova, P. Carbonelle, A. Walcarius Synth. Met. 1998, 95, 75.
et al., Electrochim. Acta 1992, 37, 725. 147. G. Schukat, E. Fanghänel, J. Prakt. Chem.
122. K. Yamamoto, E. Tsuchida, H. Nishida 1985, 327, 767.
et al., J. Electrochem. Soc. 1992, 139, 2401. 148. J. Morand, L. Brzezinski, C. Manigand, J.
123. S. Boryczka, D. Elothmani, Q. T. Do et al., Chem. Soc., Chem. Commun. 1986, 1050.
149. M. Kaplan, F. Wudl, R. Haddon et al., Chem.
J. Electrochem. Soc. 1996, 143, 4027.
Scr. 1980, 15, 196.
124. V. Z. Latypova, A. A. Chichirov, V. V.
150. Y. Siquot, P. Frere, T. Nozdryn et al., J.
Jouikov et al., Zh. Obshch. Khim. 1989, 59,
Fluorine Chem. 1997, 86, 177.
1344.
151. G. Schukat, A. M. Richter, E. Fanghänel,
125. V. Z. Latypova, A. A. Chichirov, V. V.
Sulfur Rep. 1987, 7, 155.
Jouikov et al., CA 1989, 111, 220 906.
152. T. Jorgensen, T. Hansen, J. Becher, Chem.
126. A. Bewick, D. Coe, J. Mellor et al., J. Chem.
Soc. Rev. 1994, 23, 41.
Soc., Chem. Commun. 1980, 2, 51. 153. Y. Misaki, N. Higuchi, H. Fujiwara et al.,
127. A. Bewick, D. Coe, M. Libert et al., J. Elec- Angew. Chem., Int. Ed. Engl. 1995, 34 1222.
troanal. Chem. 1983, 144, 235. 154. A. Ahrika, J. Paris, New J. Chem. 1999, 23,
128. R. S. Glass, V. V. Jouikov, N. V. Bojkova, J. 1177.
Org. Chem. 2001, 66, 4440. 155. J. Becher, J. Lau, P. Mork in Electronic
129. S. Töteberg-Kaulen, E. Steckhan, Tetrahe- Materials: The Oligomer Approach (Eds.:
dron 1988, 44, 4389. K. Mullen, G. Wagner), Wiley-VCH, Wein-
130. P. D. Machion, Ph.D. thesis, Universidade heim, Germany, 1998, p. 198.
de San Paolo, Brazil, 1993. 156. J. Simonet, J. Rault-Berthelot, Prog. Solid
131. G. Le Guillanton, S. Boryczka, D. Elothmani State Chem. 1991, 21, 1.
et al., Denki Kagaku 1994, 62, 1283. 157. G. A. Pagani, Heterocycles 1994, 37, 2069.
132. G. Le Guillanton, S. Boryczka, D. Elothmani 158. G. Tourillon, F. Garnier, J. Electroanal.
et al., CA 1995, 122, 213 703. Chem. 1982, 135, 173.
133. Q. T. Do, D. Eliothmani, G. Le Guillanton, 159. J. Roncali, Chem. Rev. 1992, 92, 711.
Tetrahedron Lett. 1998, 39, 4657. 160. P. N. Bartlett, D. H. Dawson, J. Mater.
134. R. S. Glass, V. V. Jouikov, Tetrahedron Lett. Chem. 1994, 4, 1805.
1999, 40, 6357. 161. S. Yamada, S. Tokito, T. Tsutsui et al., J.
135. D. Elothmani, Q. T. Do, J. Simonet et al., J. Chem. Soc., Chem. Comm. 1987, 1448.
Chem. Soc., Chem. Commun. 1993, 715. 162. A. G. Chang, R. L. Blankespoor, L. L. Miller,
136. R. S. Glass, V. V. Jouikov, University of J. Electroanal. Chem. 1987, 236, 239.
Arizona, to be published. 163. I. Iketone, Synth. Met. 1990, 35, 263.
137. Q. T. Do, D. Elothmani, G. Le Guillanton 164. A. Bologesi, M. Catellani, S. Destri et al., J.
et al., Tetrahedron Lett. 1997, 38, 3383. Chem. Soc., Chem. Comm. 1988, 246.
165. M. Bouachrine, T. Lakhlifi, J. Chim. Phys. 192. J. Moiroux, S. Deycard, M. B. Fleury, J. Elec-
Phys.-Chim. Biol. 1998, 95, 987. troanal. Chem. 1983, 146, 313.
166. E. Brillas, P. L. Cabot, J. A. Garrido et al., J. 193. M. Abazid, J. L. Burgot, A. Darchen et al.,
Electroanal. Chem. 1997, 430, 133. Phosphorus Sulfur 1990, 53, 425.
167. M. L. Hallensleben, M. Vanhooren, M. Pet- 194. P. Pflegel, C. Kuehstedt, P. Ritchter, Phar-
ers, Polym. Bull. 1998, 40, 167. mazie 1981, 31, 65.
168. P. Marrec, B. Fabre, J. Simonet, J. Elec- 195. P. Pflegel, C. Kuehstedt, P. Ritchter et al.,
troanal. Chem. 1997, 437, 245. Pharmazie 1982, 37, 714.
169. M. A. Odian, R. E. Noftle, J. Fluorine Chem. 196. J. Y. Becker, B. J. Zinger, S. Yatziv, J. Org.
1998, 92, 131. Chem. 1987, 52, 2783.
170. S. C. Rasmussen, J. C. Pickens, J. E. Hutchi- 197. H. Matschiner, F. Krech, A. Steinert, Z.
son, Chem. Mater. 1998, 10, 1990. Anorg. Allg. Chem. 1969, 371, 256.
171. L. Zhou, Y. Q. Li, G. Xue, Thin Solid Films 198. H. Matschiner, A. Tzschach, A. Steinert, Z.
1998, 335, 112. Anorg. Allg. Chem. 1970, 373, 237.
172. S. Funaoka, I. Imae, N. Noma et al., Synth. 199. G. Drosten, P. Mischke, J. Voss, Chem. Ber.
Met. 1999, 101, 600. 1987, 120, 1757.
173. G. Zotti, S. Zecchin, G. Schiavon et al., 200. T. Gade, M. Streek, J. Voss, Chem. Ber.
Chem. Mater. 1997, 9, 2876. 1988, 121, 2245.
174. G. T. Li, G. Kossmehl, H. P. Welzel et al., 201. J. Voss, G. Wiegand, K. Hÿlgmeyer, Chem.
Macromol. Chem. Phys. 1998, 199, 2737. Ber. 1985, 118, 4806.
175. D. J. Irvin, C. J. Dubois, J. R. Reynolds, 202. M. Falsig, H. Lund, Acta Chem. Scand. 1980,
Chem. Commun. 1999, 20, 2121. B34, 585.
176. G. Le Guillanton, J. Simonet, University of 203. A. V. Ilyasov, Y. M. Kargin, Ya. A. Levin,
Rennes, France, unpublished observations. Izv. Akad. Nauk, Ser. Khim. 1971, 4, 770.
177. K. Langner, S. Tesch-Schmidtke, J. Voss, 204. A. V. Ilyasov, Y. M. Kargin, Ya. A. Levin,
Chem. Ber. 1987, 120, 67. CA 1971, 75, 87 826.
178. S. Yasui, K. Nakamura, A. Ohno et al., Bull. 205. See, for a basic bibliography: T. Shono in
Chem. Soc. Jpn. 1982, 55, 1981. Supplement E: The Chemistry of Ethers, Crown
179. K. A. Petriashivili, V. A. Usov, L. E. Pro- Ethers, Hydroxyl Groups and their Sulfur
tasova et al., Zh. Org. Khim. 1986, 22, 575. Analogues (Ed.: S. Patai), Wiley, Chichester,
180. K. A. Petriashivili, V. A. Usov, L. E. Pro- UK 1980.
tasova et al., CA 1986, 105, 208 380. 206. R. Gerdil, J. Chem. Soc. B 1972, 1071.
181. L. E. Protasova, V. A. Usov, M. G. Voronkov, 207. M. Benaskar, J. Simonet, University of
Zh. Obshch. Khim. 1986, 56, 417. Rennes, France, unpublished observations.
182. L. E. Protasova, V. A. Usov, M. G. Voronkov, 208. J. Simonet, N. Djeghidjegh, J. Electroanal.
CA 1986, 105, 171 617. Chem. 1987, 218, 367.
183. L. E. Protasova, M. G. Voronkov, Dokl. 209. P. Martigny, J. Simonet, J. Electroanal.
Akad. Nauk SSSR 1987, 296, 653. Chem. 1977, 81, 407.
184. L. E. Protasova, M. G. Voronkov, CA 1987, 210. T. Shono, Y. Matsumura, S. Kashimura
107, 245 000. et al., Tetrahedron Lett. 1988, 29, 2807.
185. G. Mabon, J. Simonet, Tetrahedron Lett. 211. T. Shono, Y. Matsumura, S. Kashimura
1984, 25, 193. et al., Tetrahedron Lett. 1978, 1205.
186. G. Mabon, M. Cariou, J. Simonet, New J. 212. N. Schulz, S. Töteberg-Kaulen, S. Dapper-
Chem. 1989, 13, 601. held et al., Stud. Org. Chem., (Amsterdam),
187. G. Mabon, M. Cariou, J. Simonet, Univer- Recent Adv. Electroorg. Synth. 1987, 30, 127.
sity of Rennes, France, unpublished work. 213. J. Tucker, M. Gingras, H. Brand et al., J.
188. M. Largeron, D. Fleury, M. B. Fleury, Tetra- Chem. Soc., Perkin Trans. 2 1997, 7, 1303.
hedron 1986, 42, 409. 214. R. I. Pacut, E. Kariv-Miller, J. Org. Chem.
189. A. Darchen, P. Berthelot, C. Vaccher et al., 1986, 51, 3468.
J. Heterocycl. Chem. 1986, 23, 1603. 215. V. Alfonsov, O. Yakovleva, G. Evtugin, Razv.
190. M. Largeron, T. Martens, M. B. Fleury, J. Polarographii i Rodstv. Metodov Dnepropetro-
Electroanal. Chem. 1988, 252, 99. vsk 1984, 1, 169.
191. M. Largeron, T. Martens, M. B. Fleury, 216. J. F. Pilard, J. Simonet. Tetrahedron Lett.
Tetrahedron Lett. 1989, 30, 815. 1997, 38, 3735.
217. P. Iversen, H. Lund, Acta. Chem. Scand. 239. A. Orliac-Le Moing, J. Delaunay, J. Simonet,
1974, 28, 827. New J. Chem. 1994, 18, 901.
218. V. V. Zhuikov, D. S. Fattakhova, V. V. Ivkov 240. J. Delaunay, A. Orliac, J. Simonet, Tetrahe-
et al., Russ. J. Electrochem. 1996, 32, 272. dron Lett. 1995, 36, 2083.
219. V. Jouikov, L. Grigorieva, Electrochim. Acta 241. J. Delaunay, A. Orliac, J. Simonet, C. R.
1996, 41, 2489. Acad. Sci. Paris 1997, 324 IIb, 269.
220. C. Degrand, H. Lund, C. R. Acad. Sci. C 242. G. Le Guillanton, J. Simonet, Tetrahedron
1980, 291, 295. Lett. 1990, 31, 3149.
221. T. Nagano, K. Arakane, M. Hirobe, Tetrahe- 243. F. D. Saeva, B. P. Morgan, J. Am. Chem. Soc.
dron Lett. 1980, 21, 5021. 1984, 106, 4121–4125.
222. P. Baroux, Thesis Université de Rennes 1, 244. F. D. Saeva, Tetrahedron 1986, 42,
1997. 6123–6129.
223. L. Suchomelova, J. Zyka, P. Zuman, J. Elec- 245. F. D. Saeva, Top. Curr. Chem. 1990, 156, 61.
troanal. Chem. 1966, 12, 144. 246. F. D. Saeva, D. T. Breslin, P. A. Matric, J.
224. L. Suchomelova, J. Zyka, P. Zuman, J. Elec- Am. Chem. Soc. 1989, 111, 1328.
troanal. Chem. 1996, 12, 194. 247. A. Ghanimi, J. Simonet, New J. Chem. 1997,
225. N. Dheghidjegh, J. Simonet, Bull. Soc. Chim. 21, 257.
Fr. 1989, 39. 248. P. Martigny, J. Simonet, G. Mousset et al.,
226. S. Diederichs, J. Simonet, Bull. Soc. Chim. Nouv. J. Chim. 1983, 7, 299.
Fr. 1997, 134, 561. 249. L. Horner, R. J. Singer, Chem. Ber. 1968,
227. J. Simonet, G. Jeminet, Bull. Soc. Chim. Fr. 101, 3329.
1971, 7, 2754. 250. R. Kossai, J. Simonet, G. Jeminet, Tetrahe-
228. J. Simonet in The Chemistry of Sulfones dron Lett. 1979, 1059.
and Sulfoxides, (Eds.: S. Patai, Z. Rappoport, 251. G. Le Guillanton, Q. T. Do, J. Simonet, Fr.
C. J. M. Stirling), John Wiley & Sons, Chich- Demande FR 90 14,006, 1990.
ester, 1988, pp. 1001–1045. 252. G. Le Guillanton, Q. T. Do, D. Elothmani
229. O. Fourets, Thesis, University of Rennes 1, et al., Fr. Demande FR 90 10,217, 1990.
2000. 253. G. Le Guillanton, Sulfur Rep. 1992, 12, 405.
230. L. Klein, D. G. Peters, O. Fourets et al., The- 254. Q. T. Do, Thesis, University Rennes 1, 1988.
sis, Indiana University, to be published. 255. H. Berge, B. Struebing, S. Strasen et al.,
231. Lack of the cleavage regioselectivity can Ger. (East) DD 152,586, 1981.
be brought either by the substituents 256. H. Berge, B. Struebing, S. Strasen et al., CA
bulkiness, see B. Lamm, J. Simonet, Acta 1982, 96, 225 400.
Chem. Scand. 1974, B28, 147. 257. G. Bosser, M. Benaichouche, R. Coudert
232. or by the nature of substituents, see et al., New J. Chem. 1994, 18, 511.
J. Delaunay, G. Mabon, M. Chaquid El 258. J. Robert, M. Anouti, G. Bosser et al., J.
Badre et al., Tetrahedron Lett. 1992, 33, Chem. Soc. Perkin Trans. 1995, 2, 8, 1639.
2149. 259. M. Genesty, C. Degrand, New J. Chem. 1998,
233. M. Benaskar, J. Simonet, Tetrahedron Lett. 22, 349.
1994, 35, 1727. 260. A. Kunugi, K. Kuwamura, H. Uno, Elec-
234. A. Ghanimi, B. Fabre, J. Simonet, New J. trochim. Acta 1997, 42, 2399.
Chem. 1998, 22, 831. 261. G. Le Guillanton, Q. T. Do, J. Simonet, Bull.
235. P. Cauliez, M. Benaskar, J. Simonet, Elec- Soc. Chim. Fr. 1990, 127, 427.
trochim. Acta 1997, 42, 2191. 262. K. Gewald, Lect. Heterocycl. Chem. 1982, 6,
236. L. J. Klein, D. G. Peters, O. Fourets et al., J. 121.
Electroanal. Chem. 2000, 487, 66. 263. G. Le Guillanton, Q. T. Do, J. Simonet,
237. J. Delaunay, A. Orliac, J. Simonet, J. Elec- Tetrahedron Lett. 1986, 27, 2261.
trochem. Soc. 1995, 142, 3613. 264. L. Contreras, S. Rivas, R. Rozas, J. Elec-
238. J. Delaunay, G. Mabon, A. Orliac et al., troanal. Chem. Interfacial Electrochem. 1984,
Tetrahedron Lett. 1990, 31, 667. 177, 299.
277
10
Electrochemistry of
Nitrogen-containing Compounds
Kevin D. Moeller
Washington University, St. Louis, Missouri
10.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
10.2 Oxidation of Amines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280

10.2.1 Amine Radical Cations as Electrochemical Mediators . . . . . . . . . . . 281
10.2.2 Functionalization Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
10.2.3 N-centered Radicals and Cycloadditions . . . . . . . . . . . . . . . . . . . . 285
10.3 Kolbe Oxidations and the Formation of N-Acyliminium Ions . . . . . 288
10.4 The Anodic Oxidation of Amides . . . . . . . . . . . . . . . . . . . . . . . . 290

10.4.1 General Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
10.4.2 Adding Functionality to Synthetic Starting Materials . . . . . . . . . . . 291
10.4.3 Mediated Reactions and the use of Electroauxiliaries . . . . . . . . . . . 294
10.5 The Application of Amide Oxidations to the Synthesis of Natural

Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........ . 297
10.5.1 The Synthesis of Azathymine Derivatives . . . . . . . . . . ........ . 297
10.5.2 Octahydroisoquinolines . . . . . . . . . . . . . . . . . . . . . ........ . 298
10.5.3 ACE Inhibitors A58365A and A58365B . . . . . . . . . . . ........ . 298
10.5.4 (3R, 5R, 8aR)-3-n-Butylindolizidine . . . . . . . . . . . . . ........ . 300
10.5.5 Bulgecin C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........ . 301
10.5.6 (±)-Anatoxin A . . . . . . . . . . . . . . . . . . . . . . . . . . . ........ . 302
10.6 The Synthesis of Constrained Peptidomimetics . . . . . . . . . . . . . . . 302

10.6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
10.6.2 The Synthesis of Constrained TRH Analogs . . . . . . . . . . . . . . . . . 303
10.6.3 Sequential Amide Oxidation – Olefin Metathesis Strategies . . . . . . 306
10.6.4 Substance P Analogs and an Approach to Piperazinone Rings . . . . . 307
278 10 Electrochemistry of Nitrogen-containing Compounds
10.7 Amide Oxidations and the Construction of Combinatorial Libraries . 307
10.8 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309

Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
279
10.1 have high-oxidation potentials, they are

Introduction often difficult to oxidize using chemical
reagents [4]. In addition, the alkoxy prod-
From a synthetic perspective, the anodic ucts (4) typically generated have oxidation
oxidation of molecules that contain amines potentials that are only 150 to 200 mV
and amides remains one of the most higher than that of the initial amide start-
important classes of electrochemical re- ing materials. Hence, a selective oxidation
actions studied to date. The value of these is needed in order to avoid overoxidation
reactions is derived from the vast num- of the product. For chemical oxidants, this
ber of biologically active molecules that selectivity can be difficult to achieve, es-
contain nitrogen atoms and also from the pecially in the context of developing a
often unique opportunity electrochemistry generally useful synthetic method. For ex-
offers for rapidly building these molecules ample, consider a chemical oxidant having
by selectively functionalizing readily avail- the appropriate window of reactivity such
able amine and amide starting materials. that an amide substrate (1) can be oxidized
In many cases, chemical alternatives to the without overoxidizing the alkoxy product
electrochemical approach are not available. (4). If an electron-donating substituent is
Hence, the electrochemical oxidation of added to the substrate that lowers its oxida-
amines and amides provides an outstand- tion potential by 200 mV (an alkyl group),
ing backdrop for illustrating the synthetic the required selectivity for the reaction
potential electrochemistry has for ‘‘open- would be lost and the product oxidized.
ing up’’ entirely new pathways for the The addition of an electron-withdrawing
construction of molecules. group to the substrate would render the ox-
This idea is perhaps easiest to il- idation potential of the substrate too high
lustrate for the oxidation of an amide for use by the chemical reagent. The result
(Scheme 1). Amide oxidation reactions is that chemical reagents that can affect
are of tremendous synthetic interest be- the selective oxidation of an amide are by
cause they can provide an oxidative al- their nature limited in scope.
ternative to the synthesis of reactive N - Electrochemical oxidations have no such
acyliminium ion intermediates (3). Such difficulty. The potential of an anode
a route would complement well the exist- surface can be varied widely without
ing reductive and condensation-based ap- losing the selectivity of the oxidation. In
proaches [1–3]. However, because amides the scenario outlined above, the potential
−e, −H+
OR
N ROH N
CHO CHO
(1) (4)
ROH
−e
−H+
• −H+
+ − ⊕
N H −e N
CHO CHO
(2) (3)
Scheme 1 Anodic alkoxlation of N-formyl pyrrolidine.
would be lowered for a substrate having complicated equipment, the complexity of

the electron-donating group and raised the reaction setups, and the generality of
for the substrate having the electron- the reactions studied often limit accep-
withdrawing group. In both cases, the tance of the methodology developed by the
difference in oxidation potential between larger synthetic community. In practice,
the substrate and the alkoxy product these concerns rarely represent insur-
would ensure that overoxidation of the mountable barriers. The equipment neces-
product could be avoided. As outlined sary for trying the majority of electrochem-
in Sects. 10.4 to 10.7 below, this is not ical synthetic methods can be very sim-
simply a theoretical argument. Anodic ple [5], the concepts needed for conducting
amide oxidations have proven to be very the vast majority of synthetic experiments
useful synthetic tools and can provide new can be readily explained [6], and the gen-
and powerful strategies for constructing erality of the reactions are often superb
complex organic molecules. (vide infra). Since detailed discussions of
While anodic amide oxidations have these topics can be found elsewhere [7, 8],
found the most synthetic use to date, they will not be discussed here. Instead, the
the oxidation of nitrogen-containing mole- review that follows will seek to place the ox-
cules is not limited to amide substrates. A idation of nitrogen compounds into a syn-
variety of amine oxidations have been stud- thetic context. In doing so, it is hoped that
ied, and the Kolbe electrolysis of carboxylic this work will enable readers to identify not
acids has been used to generate nitrogen- only what reactions are available but also
based reactive intermediates. Many of identify how the reactions can be utilized
these reactions also offer unique synthetic to develop new strategies for synthesis.
advantages (Sects. 10.2 and 10.3).
For any synthetic method, it is important
to define the experimental setup required 10.2
for the reactions so that new users can Oxidation of Amines
take advantage of the chemistry. This is
especially important for electrochemistry The formation of a radical cation inter-
in which misgivings about the need for mediate normally initiates reactions that
10.2 Oxidation of Amines 281
fall into one of three main categories. surface and the cycle continues. These re-
In the first category, the radical cation actions have been reviewed previously [9].
intermediate generated oxidizes a second However, a pair of recent experiments
substrate in the reaction medium. This deserves comment here because they illus-
results in a mediated oxidation of the sec- trate the potential utility of these reactions.
ond substrate. In the second category, the The use of a chemical mediator can
radical cation generated undergoes an ad- alter the chemoselectivity of an electro-
ditional reaction with either an olefin or a chemical reaction. In the reaction illus-
nucleophile. In the third category, the elim- trated in Scheme 2, β-methylstyrene was
ination of a neighboring group of the radi- oxidized using both direct electrolysis
cal cation leads to the formation of an elec- and mediated conditions [10]. The cur-
trophile that either traps a nucleophile or rent density, amount of charge passed,
undergoes a second elimination reaction temperature, and other variables were
in order to generate an unsaturated prod- all kept constant. The only difference
uct. All three of these reaction types have was the addition of 6.4 mole percent of
been triggered by the oxidation of an amine tris(4-bomophenyl)amine to the mediated
to form a nitrogen-based radical cation. reaction. The direct electrolysis tended to
afford the product of a four-electron oxida-
10.2.1 tion (7). When 3.5 F mole−1 of electricity
Amine Radical Cations as Electrochemical was passed, a 55% yield of (7) was ob-
Mediators tained along with a 45% yield of (6). With
additional current (6.4 F mole−1 ), a 75%
A variety of amines have been used as yield of (7) was obtained. The mediated
mediators for electrochemical oxidation re- process led to a preponderance of the prod-
actions. In these reactions, the amine is uct from the two-electron oxidation. When
oxidized at an anode surface to form a rad- 3.5 F mole−1 of electricity was passed in
ical cation. The amine radical cation then the experiment using the triarylamine me-
oxidizes a second substrate triggering a diator, a 93% yield of (6) was obtained
reaction of synthetic interest. The regener- along with only 6% of the four-electron
ated amine is then reoxidized at the anode oxidation product.
OMe OMe
Carbon anode
3.5 F mole−1 OMe
Curent density = 15 mA cm−2 OMe
Temperature = 18 °C
(5) (6) (7)
Without mediator: 45% 55%

With mediator: 93% 6%
Br N
Scheme 2 Anodic methoxylation of β-methylstyrene without and with an amine radical cation
as mediator.
In many cases, mediators are used representative examples are illustrated in

to regenerate chemical reagents. Such Scheme 4.
reactions are advantageous because they
capitalize on the advantages of elec- 10.2.2
trochemistry and the selectivity associ- Functionalization Reactions
ated with the chemical reaction. For
example [11], a tris(4-bromophenyl)amine- In addition to using amine oxidation
mediated reaction has been utilized to products as mediators, anodic oxidation
effect the Wacker process (Scheme 3). The reactions can be used to functional-
reactions were conducted using either a ize amine compounds. These reactions
divided cell with 5 mole percent Pd(OAc)2 include both – examples that generate
catalyst or an undivided cell with 5 mole imines and nitriles, as well as examples
percent PdCl2 catalyst. In both cases, the that lead to the addition of nucleophiles to
Pd (0) generated from the reaction was the carbon alpha to the nitrogen.
reoxidized to the Pd (II) species required The electrochemical oxidation of amines
for the reaction by two equivalents of the to imines and nitriles typically utilize a
amine radical cation. The amine radical chemical mediator. The use of both N -oxyl
cation was then regenerated using a plat- radicals [12, 13] and halogens has been
inum anode. Both reaction setups used reported for this process [14]. For exam-
20 mole percent of the mediator along ple, the conversion of benzyl amine (14a)
with a 0.5 M Et4 NOTs in a 7 : 1 ace- into nitrile (15a) and aldehyde (16a) has
tonitrile/water electrolyte solution. Two to been accomplished using the N -oxyl radi-
three F mole−1 of electricity was passed in cal of a decahydroquinoline ring skeleton
each case. Using these conditions, a se- as the mediator (Scheme 5). The use of
ries of nine monosubstituted olefins were acetonitrile as the solvent for the reaction
converted into the corresponding methyl generated the nitrile product. The addition
ketones. The reactions tolerated the pres- of water to the reaction stopped this pro-
ence of aryl rings, ethers, ketones, esters, cess by hydrolyzing the imine generated. A
carbamates, and alcohols and afforded high yield of the aldehyde was obtained. In
yields that ranged from 66 to 93%. Two the case of a secondary amine, the aqueous
Pd (II) 2 Br N
R
3
+H2O Anode
O •+
Pd (0) 2 Br N
R 3
Scheme 3 Electrochemical Wacker process with amine radical cation-mediated Pd(II) regeneration.
Undivided cell
Pt anode
5 mole % PdCl2
(1) O
CH3CN/H2O (7 : 1)
O Et4NOTs O
O O
Br N
(10) 3 (11) (85%)
CO2Me Same conditions CO2Me

(2)
O
O O
(12) (13) (90%)
Scheme 4 Electrochemical Wacker processes.
Graphite anode
NH2 divided cell N O
(+0.6 V vs. Ag/AgCl) C
R + R
NaClO4, 2, 6-lutidine
OCOPh
(14) H (15) (16)
O•
R Solvent
a H CH3CN 87% 4%
4 : 1 CH3CN/H2O – 95%
b CH3 4 : 1 CH3CN/H2O – 88%
Scheme 5 Mediated anodic oxidation of amine to nitrile and carbonyl compound.
conditions were used to generate a ketone same as in the aqueous cases illustrated
product. Several examples were reported in Scheme 5. The reactions were run to
including the oxidation of both the primary partial conversion and then the chirality of
and the secondary aliphatic amines. the recovered amine-starting material was
Recently, a similar reaction has been measured. Enantiomeric excesses of 62 to
shown to affect the kinetic resolu- 78% were obtained. The turnover number
tion of racemic secondary amines (Sch- for the N -oxyl radical ranged from 21.7
eme 6) [15]. In this example, N -oxyl radical to 26.5.
(20) was utilized as the mediator. The rest The direct oxidation of tertiary amines
of the reaction conditions remained the leads to the formation of an iminium
Graphite anode
NH2 divided cell O NH2
(+0.8 V vs. Ag/AgCl)
R1 R2 R1 R2 + R1 R2
NaClO4, 2, 6-lutidine
O
(17) (R1 = Aryl NH (18) (54–66%) (19) (34–46%
R2 = Me, 62–78% e.e.)
4 examples)
O•
Scheme 6 Kinetic resolution in the oxidation of a rac-sec amine with a non racemic nitroxyl mediator.
ion followed by subsequent trapping substrate that resulted from the opening
with a nucleophile. As illustrated in of the tetrahydrofuran ring in the sub-
Scheme 7, Fuchigami and coworkers re- strate. The oxidation led to the radical
ported the anodic cyanation of 2,2,2- cation of the enamine that underwent a
trifluoroethylamines [16]. In these exper- subsequent reaction with an oxidized bro-
iments, no oxidized product was obtained mide (Br• ) to generate an α-brominated
alpha to the trifluoromethyl group. This iminium ion. Elimination of a proton to re-
result was curious since α-methoxylation generate the enamine, oxidation to reform
reactions showed the exact opposite se- the enamine radical cation, and trapping
lectivity and favored methoxylation on of a second bromine radical again led to an
the carbon alpha over the trifluoromethyl iminium ion. Recyclization afforded the
group [17]. The mechanism of the cyana- bicyclic product.
tion reaction clearly proceeded through The oxidation of an amine can benefit
the formation of an iminium ion. How- from the use of an electroauxiliary [19–28].
ever, it was not clear why this reaction Electroauxiliaries are substituents that
differed so dramatically from the methoxy- both lower the initial oxidation potential
lation process. of the substrate and control the formation
Similar oxidations also occurred with of the subsequent reactive intermediates.
enamine substrates. In the reaction out- To this end, the anodic oxidation of
lined in Scheme 8 [18], the formation of the 6-membered ring α-silylamines in
a dibrominated product arose because the presence of cyanide was shown to
of the initial oxidation of an enamine afford a net displacement of the silyl
CN
Pt anode
NCH2CF3 0.5 M NaCN/ MeOH
NCH2CF3
Divided cell
3.0 F mole−1
(20) (21) (54%)
Scheme 7 Anodic α-cyanation of amine.

Ph Ph
Pt anode
Et4NBr
NC N O NC N O
LiClO4, CH3CN
controlled potential Br
+0.7 V vs. SCE
Br
(22) (23) (82%)
Scheme 8 Anodic conversion of an amine to an enamine with subsequent anodic bromination.
group by cyanide (Scheme 9) [29]. Both initial amine radical cation followed by a
aliphatic and aromatic cases were studied. second oxidation. Finally, the conversion
The reactions were much more selective of the silylated amine to the α-cyanoamine
than the cyanations involving the direct required only 2 F mole−1 of electricity.
oxidations of amines. For example, when Earlier direct oxidations required up to
(24) was oxidized at an anode surface an 4 F mole−1 due to a homogenous electron
inseparable mixture of three products was transfer between the cyanide anion and
obtained. In contrast, the oxidation of (25) the radical cation in solution. The authors
led to the formation of just one product. argued that the increase in efficiency
Three items concerning this reaction arose because of the ability of the cyanide
deserve further comment. First, substrate anion to accelerate the elimination of the
(25) was readily available by metallation silyl group from the radical cation. This
and silylation of the t-butyliminomethyl- decreases the lifetime of the radical cation
protected 3-methylpiperidine. The reaction and reduces the chance for a homogenous
led to an 85% isolated yield of the product electron transfer.
silylated at the 6-position of the piperidine
ring. Second, the stereochemistry of the 10.2.3
cyanation reaction arose because of a N-centered Radicals and Cycloadditions
stereoelectronic addition of cyanide to
the iminium ion generated from the In addition to generating amine radical
elimination of the silyl group from the cation mediators and functionalizing
Me Flow cell Me Me Me
graphite felt anode
LiOAc, MeOH + +
N NC N N CN N
NaCN
Ph Ph Ph NC Ph
(24)
Me Flow cell Me
graphite felt anode
N SiMe3 LiOAc, MeOH N CN
NaCN
Ph Ph
(25) (26) (85%)
Scheme 9 Regioselective anodic cyanation of amine (25) by way of an electroauxiliary.

amine substrates, anodic oxidation reac- For cases directly comparable to the
tions can be used to trigger nitrogen- cyclization originating from (27) above,
based radical chemistry. An example of the yields of the product were not as
this chemistry is illustrated in Sche- high. However, a related reaction used
me 10 [30, 31]. In both the reactions il- in the synthesis of an 11-substituted
lustrated, the amines were treated with dibenzo[a,d]-cycloheptenimine derivative
n-BuLi and the resulting anion oxidized at was very successful as shown in Scheme 11
a platinum anode using constant current (Eq. 2) [32]. In this reaction, a controlled
conditions, a divided cell, and a lithium potential electrolysis of (33) led to the
perchlorate in THF/HMPA (30 : 1) elec- formation of the tetracyclic (34) in an
trolyte solution. The one-electron oxidation 85% isolated yield. The reaction was per-
led to the formation of the nitrogen-based formed on a 1 g scale using an undivided
radical that then added to the olefin to form cell, a graphite felt anode, a stainless
a cyclic product. Abstraction of a hydrogen steel cathode, a saturated calomel refer-
atom from the solvent afforded products ence electrode, and a 1% NaBF4 in 70 : 30
(28) and (30). Oxidation of the amines THF/water electrolyte solution. The elec-
without prior treatment with n-BuLi failed trolysis was scaled up further with the use
to afford cyclic products. In cases where of a flow cell. In this experiment, 200 g of
n-BuLi was used, the reactions were both (33) were oxidized in order to afford a 75%
stereo- and regioselective. For reactions isolated yield of (34).
originating from (27) only cis-pyrrolidine Another oxidative cyclization to afford
products were obtained. The product (30) a nitrogen heterocycle is illustrated in
was used further to complete the synthesis Scheme 12 [33]. This reaction was accom-
of (+)–N -methylanisomycin [31]. plished using a platinum gauze electrode
The direct oxidation of unsaturated N - at a controlled potential of +1.8 V versus
methoxy amines also leads to the forma- Ag/AgCl. The reaction proceeded through
tion of cyclic products (Scheme 11) [30]. the initial oxidation of the amide. Evidence
1. nBuLi, THF
2. Pt anode
THF, HMPA
(1)
R NH 0.25 M LiClO4 R N
C6H5 divided cell C6H5
CH3 1.2 F mole−1, −10 °C CH3
(27) (R = H, CH3, Ph) (28) (66–85%)
MOMO OMOM MOMO OMOM
Same as above
(2) NH N
53%
CH3 CH3
(29) OMe (30)

OMe
Scheme 10 Regio- and stereoselective anodic cyclization of amides.

Carbon anode
constant current
(1) R R
NH 0.25 M NaBF4 N
Ph THF/MeOH/H2O Ph
OCH3 (10 : 1 : 1) OCH3
(31a) (R = CH3) (32a) (42%)
(b) (R = Ph) (b) (38%)
OH
Carbon anode
undivided cell
controlled pot. X
(2)
(+1.2 V vs. SCE)
Me NH 1% NaBF4
THF/ H2O Me
OMe
(33) (34) (X = NOMe; 85%)
Scheme 11 Regioselective anodic cyclization of O-Methyl hydroxylamines.
O O
Pt gauze anode
(+1.8 V vs. Ag/AgCl)
X X
LiClO4, CH3CN
HN O N O
(X = Y = H; yield = 75%)
(35) (36)
Y Y
Scheme 12 Intramolecular anodic amination of aromatics.
for this conclusion was obtained by placing reactions (Scheme 13) [34]. In these ex-
substituents on the two phenyl rings of periments, a LiClO4 in acetonitrile so-
the substrate. It was found that sub- lution containing a 2-vinylpyrrole and a
stituents in position X did not influence β-acceptor substituted enamine was elec-
the initial oxidation wave obtained for trolyzed at a controlled potential in an
the substrate, while substituents in posi- undivided cell. As in the case illustrated, it
tion Y did. Electron-withdrawing groups in was not always clear which substrate un-
this position raised the oxidation potential derwent the oxidation. Both (37) and (38)
for the substrate, while electron-donating have similar oxidation potentials (Ep =
groups in position Y lowered the ob- +0.85 and +0.86 respectively). The re-
served oxidation potential. Formation of sult was a [4+2]-cycloaddition reaction
the nitrogen-based radical was followed by between two substrates having nearly iden-
the cyclization reaction. A second oxida- tical HOMO energies. Cyclic voltammetry
tion reaction followed by loss of a proton data indicated that the cycloaddition reac-
and reestablishment of the aromatic ring tions were diffusion-controlled processes.
afforded the cyclic product. In all cases, the product generated was a
Amine-based radical cations have also single regioisomer. The yield for the re-
served as participants in cycloaddition action varied from 23 to 66% (10 cases).
Carbon anode
CN
carbon cathode CN
CN + N
Undivided cell
N N Ag/ AgNO3 ref. electrode
CN
CN 0.1 M LiClO4, CH3CN
H CN
(37) (38) (39) (60%)
Scheme 13 Anodic cycloaddition.
It is important to note that the reactions converted immediately to either an alco-

are fundamentally different from simi- hol or an iodide secondary product. The
lar radical cation Diels–Alder reactions reactions worked well with either mono-
initiated with the use of a photochem- substituted or disubstituted olefins. In-
ical electron-transfer reaction [35, 36]. In terestingly, when 1,1-disubstituted olefins
photochemical reactions, a one-electron were used the reactions led to the forma-
oxidation of the substrate leads to a cy- tion of substituted oxazoles in good yields
cloaddition that is then terminated by a (Scheme 15). These products formed from
‘‘back electron transfer’’. No net change an initial addition of the nitrate radical to
is made in the oxidation state of the sub- the olefin, oxidation of the resulting ter-
strate. However, the reaction outlined in tiary radical to a cation, and the trapping
Scheme 13 involves a net two-electron ox- of the cation with acetonitrile. A loss of
idation of the substrate. Hence, the two NO2 + led to the observed cyclic product.
pathways are complementary.
Finally, the oxidation of nitrate anions
leads to nitrate radicals (NO3 • ) that add 10.3
to olefins (Scheme 14) [37]. These oxida- Kolbe Oxidations and the Formation of
tions were carried out at a platinum anode N-Acyliminium Ions
using constant current conditions, an un-
divided cell, a mixed MeCN : H2 O : Et2 O One of the best-known anodic oxidation
solvent system, and LiNO3 as the elec- reactions is still the Kolbe electrolysis [38].
trolyte. The initial oxidation led to a nitrate These reactions typically involve the de-
product that was not stable and hence carboxylation of a carboxylic acid and
Pt anode
LiNO3 ONO2 NaSH OH
C4H9 C4H9 C4H9
Constant current H2O
CH3CN/ H2O/ Et2O
(40) (41) (65%)
undivided cell
NaI
acetone
I
C4H9
(42) (67%)
Scheme 14 Anodic addition of nitrate anions to double bonds.

10.3 Kolbe Oxidations and the Formation of N -Acyliminium Ions 289
Pt anode R2 R3
R1 R1
LiNO3
R2 R3 Constant current N O
CH3CN/H2O/Et2O
undivided cell CH3
(43) (44) (69–77%)
Scheme 15 Anodic addition of a nitrate anion and acetonitrile to a double bond.
Anodic oxid.
OH O•
R1 −H+ R1
O O
RCO2H R1 = OR, NR2

R1 R • −e− +
R• R1
R1
Scheme 16 Anodic decarboxylation: radical and cationic pathway.
the formation of a radical intermediate the N -acyliminium ion intermediate gen-

(Scheme 16). The radical intermediates erated. The resulting product (46) was then
have been used to trigger a wide variety used as a key intermediate in the asym-
of both intermolecular and intramolec- metric synthesis of the β-lactam natural
ular coupling reactions. However, the product (+)–PS-5. In the second exam-
formation of the radical intermediate and ple [40] (Scheme 17, Eq. 2), the oxidation
subsequent coupling reactions can be dra- of (47) in methanol solvent led to the for-
matically altered by the nature of the mation of the methoxylated amide (48)
substrate. If a heteroatom is present on in high yield. In this case, the product
the alpha carbon of the original acid, then was converted into a variety of functional-
the reactions lead to cationic intermedi- ized products. Along these lines, bicyclic
ates. For example, the anodic oxidation (49) was formed by allylating (48) with
of N -acyl protected amino acids leads allylbromide, treating the resulting prod-
to the formation of N -acyliminium ion uct with allylsilane and BF3 • Et2 O, and
intermediates. then effecting an olefin metathesis re-
Because of the efficiency of this pro- action. Tricyclic (50) was generated by
cess, the anodic oxidation of amino treating the methoxylated amide (48) with
acid precursors can serve as an excel- 1-bromo-2-phenylethane and then effect-
lent method for generating chiral building an intramolecular cyclization reaction
ing blocks for synthesis. For example with TiCl4 . Finally, the oxidation of (51)
(Scheme 17, Eq. 1) [39], the anodic oxi- afforded the chiral cationic glycine equiv-
dation of (45) was accomplished at a alent (52) (Scheme 17, Eq. 3) [41]. This
platinum anode using an undivided cell. intermediate was useful for the synthesis
An acetate nucleophile was used to trap of amino acid derivatives.
H H
H CO2H −e− OAC
Pt anode 4 steps R
(1) N
NH Undivided cell NH
O O
O NaOAc CO2H
(45) MeOH/AcOH (46)
84% (+)−PS-5 (R = S(CH2)2NHAc)
O O O
Carbon anode
HN MeOH HN 3 steps N
(2)
NaOAc
−1
HO2C Me 2.5 F mole MeO Me Me
(47) 85%
(48) (49)
2 steps O
N
O
Me
(50)
O O HO2C NH2
(3) N Anodic N 2 steps
NH Oxid. MeOH NH
O 70% O
CO2H OMe
(51) (52) (53)
Scheme 17 Generation of N-acyliminium ions by anodic decarboxylation.
In a related series of reactions, Seebach oxidation reaction involves the direct

and coworkers decarboxylated amino acids conversion of amides to N -acyliminium
to make peptide-based building blocks ions (Scheme 19). This reaction, initially
(Scheme 18) [42, 43]. In this work, 13 ex- discovered by Ross, Finkelstein, and Peter-
amples were tried with yields ranging from son [44–46], complements existing chem-
25 to 98%. Treatment of the methoxylated ical methods that employ either the re-
products with Lewis acid was used to induction of an imide or the condensation
troduce both allyl and phosphonate-based of an amide and an aldehyde to make
nucleophiles into the molecules. N -acyliminium ions. The power of the ox-
idative method lies in its ability to quickly
make reactive intermediates from known
10.4 amine and amino acid starting materi-
The Anodic Oxidation of Amides als. Because of the reactions utility, the
10.4.1 early work concerning the synthetic po-
General Reaction tential of anodic amide oxidation reactions
has been extensively reviewed [47]. Since
As mentioned in the introduction, one the appearance of that review, the anodic
of the most synthetically useful anodic amide oxidation reaction has continued to
10.4 The Anodic Oxidation of Amides 291
H H
O Me Pt or glassy carbon O Me
anode
N N
Cbz N COOH Undivided cell Cbz N OMe
Me MeOH, 2.3 F mole−1 Me
H EtN(i-Pr)2 H
(54) (55) (82%)
Scheme 18 N-α-methoxylation in peptides by anodic decarboxylation.
O O
R R •+
Anodic oxid.
N N
MeOH
−e−, −H+
O O
R R +
+MeOH
N N
−H+
MeO
Scheme 19 Anodic conversion of amides to N-acyliminium ions.
be effectively utilized for the synthesis of involves the conversion of readily avail-
complex organic molecules. This work falls able starting materials into useful synthetic
into three main categories; the construc- building blocks. This is accomplished by
tion of small molecule building blocks, using the oxidation reaction to selectively
the synthesis of natural products, and the functionalize the starting material. For ex-
synthesis of constrained peptidomimetics. ample, the conversion of p-methoxyanilide
derivatives into quinone N -acylimine ke-
10.4.2 tals has been effected at a platinum anode
Adding Functionality to Synthetic Starting (Scheme 20) [48]. Related efforts have ex-
Materials plored the compatibility of the oxidations
with both substituents on the aromatic
One of the most practical applications ring and a variety of protecting groups on
of the anodic amide oxidation reaction nitrogen. In this work, the quinone imine
O O
H
N R N R
Pt anode
MeOH
LiClO4/ NaHCO3
constant current
OMe undivided cell MeO OMe
(56) (57) 60–80%
Scheme 20 Anodic conversion of p-methoxyanilide to quinone imine.

acetals (57) were obtained in yields ranging anode in acetic acid using an undivided
from 62 to 97% [49]. cell and constant current conditions.
Anodic amide oxidations have also Oxidation led initially to the α-acetoxy
proven useful for selectively converting amide that then underwent elimination
amides into enamides that have in turn to the enamide. Anodic oxidation of
been used to functionalize the carbon the enamide then led to the diacetoxy
beta to nitrogen. For example, the four- compound that upon heating afforded the
electron oxidation of carbamates was used β-acetoxy enamide (59). Hydrolysis then
to introduce a carbonyl beta to a nitrogen afforded the desired β-ketoamide.
(Scheme 21) [50]. In this example, the In a related set of reactions, anodic
starting carbamate was oxidized at a carbon amide oxidation reactions have been
Pt anode
undivided cell
KOAc, HOAc
R N R N OAc R N
constant current
12 F mole−1 CO2Me CO2Me
CO2Me
(58)
O OAc OAc
Na2CO3 Heat
R N MeOH R N −HOAc R N OAc
CO2Me CO2Me CO2Me

(60) (72–95%) (59) (R = H, 75%
R = Me, 57%)
Scheme 21 Anodic β-oxidation of amides via enamides.
R Pt anode R OMe
undivided cell
R1 NHCO2Me Et4NBF4, MeOH R1 NHCO2Me
const. current (300 mA)
−10 °C
(61) (62) (58–86%
5 cases)
NaH, THF
reflux
R1 NHCO2Me
(63) (56–97%)
Scheme 22 Enecarbamates by anodic oxidation of amides.

used to make enecarbamates in acyclic current conditions and enabled the synthe-
systems (Scheme 22) [51]. The oxidation sis of 12 g of product. The methoxylated
reactions were typically done on a 6-g amide obtained was used to generate
scale. The desired enecarbamate products precursors of pyrrolidine azasugar deriva-
were then formed using a base-catalyzed tives (66) [54]. Using the same conditions,
elimination of the methoxy group. In this the methoxylated amide (68) could be
work, the enecarbamate products were made on a 5-g scale [53]. Compound (68)
subsequently hydroborated in order to was used as a precursor of the series
form β-hydroxy carbamates. of bicyclic lactam intermediates (69) and
In addition to elimination reactions, (70) [55].
the methoxylated amide products from Kise and coworkers have shown that
electrolysis reactions have been treated organozinc reagents can be added to
with a variety of nucleophiles [47]. In electrochemically derived N -acyliminium
recent studies, these efforts have been ions. These reactions have been used
utilized to expand the chiral pool of to synthesize β-amino acid derivatives
starting materials available to synthetic (Scheme 24) [56].
chemists. For example, consider the re- In an another analogous set of reac-
actions illustrated in Scheme 23 [52, 53]. tions, Matsumura and coworkers have
In these efforts, Steckhan and cowork- shown that electrochemically derived
ers have used the oxidation reaction to N -acyliminium ions can serve as elec-
make a stable N -α-methoxy amide that trophiles in asymmetric alkylation re-
was stored for future use. The oxidation actions (Scheme 25) [57]. In this case,
of (64) is representative of this family the methoxycarbamate of a series of
of reactions [52]. The oxidation was per- cyclic amines was oxidized in order to
formed at a carbon anode using constant generate the N -α-methoxy carbamates,
O O O
Carbon anode
constant current 3 steps
(1) HN O HN O N O
4 F mole−1; NaSO 3Ph
MeOH/Pt cathode HO
CH2Cl MeO CH2Cl H CH2Cl
HO
(64) (65) (76%) (66)
OH OTBS TBSO R R
Same
electrolysis TBDMSCl OMe 3 steps
(2)
NH conditions imidazole NH N
O O O
3 steps
(67) (68) (57%) OTBS (69)
N
O
(70)
Scheme 23 Building blocks for the chiral pool by anodic α-methoxylation of amides.
OTBS OTBS
Br +
NHCO2Me NHCO2Me
OTBS Zn/HOAc
X 68% (72) (73)
(72/73 > 9)
NHCO2Me
O
(71a) (X = H) OTBS OTBS
a. Br
(71b) (X = OMe) OtBu
CO2tBu + CO2tBu
Zn/HOAc
56% NHCO2Me NHCO2Me
(74/75 > 9)
(74) (75)
Reagents: a) Carbon anode, MeOH, Et 4NOTs, 2.0 F mole −1, 62%
Scheme 24 N-α-methoxylation of carbamates and further conversion of the methoxy products.
O O
Ph
N ( )n
( )n O O O
*
N *
N X N
TiCl4, i -Pr2NEt Ph O
MeO2C
O OMe CH2Cl2, −78 °C to RT
a. (76a) (n = 1–3, X = H) (77) (Yield = 52–59%

(76b) (n = 1–3, X = OMe) erythro/threo = 5.6 to
18% ee = 93–99)
Reagents: a) Carbon anode, MeOH, Et 4NBF4, 2.3 F mole−1, 85% (n = 2)
Scheme 25 N-α-methoxylation of carbamates and diastereoselective substitution of the

methoxy group.
which were treated with a chiral enolate prove problematic. Typically, they utilize
equivalent. The reactions resulted in the a halogen electrolyte that is oxidized at
formation of enantiomerically enriched the anode surface to form a reactive ‘‘X+ ’’
methylphenidate precursors (77). species. The X+ intermediate then reacts
with the amide nitrogen. A subsequent
10.4.3 elimination reaction generates the desired
Mediated Reactions and the use of N -acyliminium ion. Reactions of this type
Electroauxiliaries have been used to functionalize amino
acid derivatives (Scheme 26) [58], as well
In addition to the direct oxidation of simple as to initiate oxidation – rearrangement
amides, indirect oxidations of amides sequences for building bicyclic amines
have proven useful for synthesizing chiral (Scheme 27) [59]. In the second example,
starting materials. Such reactions are the initial oxidation of (82) led to the
often employed when direct electrolyses formation of an enamine. The enamine
H
O CH3 O Carbon anode O
N undivided cell
Ph N OMe Ph N NH
5% MeOH/CH3CN
O CH3 Et4NCl/84%
H d.r. = 1.5 : 1 O CO2Me
(78) (81)
Cl
O CH3 O O CH3 O
N N
Ph N OMe Ph N OMe
O CH3 O CH3
H H
(79) (80)
Scheme 26 Cl− -mediated N-α-substitution of a dipeptide.
NHAc OMe NHAc

−4e−, KI
TsHN CO2Me NaOMe/MeOH MeO CO2Me
92%
NHTs
(82) (83)
1. ∆, NH4Cl/82%
2. H 2, 78%
NH2
NHTs
Multiple steps
AcO N
MeO2C N
(85) (84)
Ac
Scheme 27 I− -mediated regioselective conversion of a diamide to an enamide with subsequent
aziridine formation and methanolysis.
then underwent a second oxidation to form starting material [19–28]. The electroaux-
an alkoxy aziridine intermediate. Trapping iliary works by donating electron density
with methanol afforded the product (83). to the group being oxidized, raising the
Finally, compound (83) was subjected energy of the HOMO and lowering the oxi-
to an intramolecular reductive amination dation potential. In the case of an amide ox-
reaction before being converted into the idation, silicon groups can serve as very ef-
bicyclic (85) using a multistep procedure. fective electroauxiliaries (Scheme 28) [60].
In addition to using indirect oxidation re- For example, the oxidation potential (mea-
actions, electroauxiliaries have been used sured using a Ag/AgCl reference electrode
to circumvent problems with problem- in a LiClO4 in acetonitrile electrolyte solu-
atic amide oxidations. As mentioned in tion) of (86) is half a volt lower than the
Sect. 10.2.2, an electroauxiliary is a group oxidation potential of (87). In addition to
that is added to a molecule in order lowering the oxidation potential of the sub-
to reduce the oxidation potential of the strate, the presence of the electroauxiliary
O O
Ph Ph
N OMe N OMe
SiMe3
CH3
(86) (Ep = +1.45 V (Ag/AgCl)) (87) (Ep = +1.95 V (Ag/AgCl))
Scheme 28 Lowering the oxidation potential of amide by an electroauxiliary.
controls the formation of the subsequent oxidations of these substrates typically lead
reactive intermediate and thus channels to poor yields of the methoxylated prod-
the reaction toward the formation of a uct (Scheme 30, Eq. 1) [61, 62]. However,
particular product. For example, the oxida- when the amides are substituted with a
tion of (88a) led to the exclusive formation silyl group on the carbon alpha to the
of the methoxymethyl-substituted amide amide nitrogen (93), the oxidation pro-
(89) (Scheme 29) [60]. Without the elec- ceeds smoothly (Scheme 30, Eq. 2).
troauxiliary, a similar reaction originating In addition to silicon, sulfur groups have
from (88b) led to a mixture of products. been used as auxiliaries for amide oxida-
In a related set of reactions, Oku and tion reactions (Scheme 31) [63]. However,
coworkers have been investigating the an- in these cases the mechanism of the
odic oxidation of acyclic amides having reaction is different. The sulfur is oxidized
alkoxy groups on the carbon alpha to to form a sulfur radical cation that is then
the amide carbonyl (91) [61]. The direct eliminated from the molecule in order to
O Carbon anode O OMe O

undivided cell
Ph N OMe Ph N OMe + Ph N OMe
0.2 M Et4OTs
MeOH, 10 mA
X OMe CH3
(88a) (X = SiMe3) (89) (97%) (90) (–)

(88b) (X = H) (89) (65%) (90) (35%)
Scheme 29 Regioselective N-α-methoxylation of amides using an electroauxiliary.
H H
OMe Carbon anode OMe
undivided cell N
(1) N
Et4NOTs, MeOH
O 20 mA (2 F mole−1) O OMe
(91) (92) (19%)

H H
OMe Carbon anode OMe
N undivided cell N
(2) C6H13 C6H13
Et4NBF4
O SiPhMe2 MeOH/CH2Cl2 O OMe
20 mA (2 F mole−1)
(93) (94) (76%)
Scheme 30 Selective N-α-methoxylation of amides using an electroauxiliary.

10.5 The Application of Amide Oxidations to the Synthesis of Natural Products 297
OTBS OTBS
H SPh Pt anode
H F
Et4NF• 3HF
N CH3CN, 2.9 F mole−1 N
Ph O Ph
O 0.1 eq. (2,4-Br 2C6H3)3N
(95) (96) (66%)
Scheme 31 Anodic substitution of an N-α-thiogroup with fluoride.
generate an N -acyliminium ion. In the molecules, it has proven to be a very useful

example illustrated, the iminium ion was tool for constructing natural products. For
trapped with fluoride. For this example, a example, Hudlicky and coworkers have
triarylamine was used as a mediator for used an anodic amide oxidation in the
this reaction in order to avoid passivation synthesis of a series of azathymine deriva-
of the electrode surface by the liberated tives [65]. In this work, the authors utilized
sulfur species [64]. the anodic amide oxidation reaction in
order to circumvent problems with an an-
ionic oxygenation reaction (Scheme 32).
10.5 When substrate (97) was treated with sec-
The Application of Amide Oxidations to the butyllithium and then oxygen, a 10 to 35%
Synthesis of Natural Products yield of the hydroxylated product (98a) was
isolated. The reaction could not be run
10.5.1 on a large scale due to safety issues. The
The Synthesis of Azathymine Derivatives authors recommend that the reaction be
run on not more than 2 mmol of mate-
Because anodic amide oxidation provides rial due to the potential for explosion. For
an excellent method for functionalizing comparison, the anodic oxidation of (97)
OR
Carbon anode
N N N N
N Et4NOTs, MeOH N
(1)
N 62% (98b) N
N O N O
H H
(97)
(98a) (R = H)
(98b) (R = CH3)
O O
X Y
N NH Carbon anode N NH
N NaOMe, MeOH N
(2)
N 97% (100a) N
N O N O
H (99) H
(100a) (X = OMe, Y = H)
(100b) (X = Y = O)
Scheme 32 Anodic N-α-methoxylation as superior route to azathymine derivatives.

led to a 62% isolated yield of the methoxy- the synthetic utility of anodic amide
lated product (98b). The anodic reaction oxidations in the synthesis of the octahy-
could be run on a 20-g scale. droisoquinolines needed for the synthesis
In a similar experiment, the anionic of morphine [66]. In this case, an elec-
oxygenation of the substrate (99) failed to trochemical route to the N -α-alkoxyamide
generate the desired hydroxylated product. (102a) was used in order to provide a
In this case, a small-scale (721 mg) anodic complementary route to a reductive ap-
oxidation reaction led to a 97% yield proach to (102b) originating from the
of the methoxylated product. For larger imide (101b) (Scheme 33). The yield of the
scale reactions, it was important to force N -α-alkoxyamide obtained from the elec-
the reaction to completion because (99) trochemical route was not as high (50%)
was difficult to remove from product as the yield obtained using the reductive
(100a). The overoxidized material (100b) approach. However, the use of the anodic
could be separated from the product by oxidation reaction did allow for flexibility in
recrystallization. With this in mind, large- terms of when the alkoxy functionality was
scale reactions of (99) (10–15 g) were introduced into the molecule and did avoid
pushed to a point where they led to 45 the use of base-sensitive intermediates like
to 50% yields of the desired product along imide (101b).
with 25% of the overoxidized (100b).
Both the methoxylated products could 10.5.3
be hydrolyzed using citric acid in wa- ACE Inhibitors A58365A and A58365B
ter/THF or KOH in water to afford the
initially desired alcohol compounds. In As seen in Scheme 33, the ability of
this chemistry, it was clear that the elec- anodic amide oxidations to functional-
trochemical protocol offered distinct ad- ize amines opened up the possibility for
vantages over the more traditional chemi- developing annulation strategies for fus-
cal route. ing rings onto amines and amino acid
derivatives [67–69]. This approach was
10.5.2 used to synthesize the ACE inhibitors
Octahydroisoquinolines A58365A and A58365B [70]. As illustrated
in Scheme 34, these two natural prod-
In addition to their work concerning ucts differed only in the size of their
the synthesis of azathymine derivatives, nonaromatic rings. For this reason, it
Hudlicky and coworkers have also explored was suggested that nearly identical routes
Anodic oxid/
OBz MeOH OBz OBz
BzO Et4NOTs/ BzO BzO
O (X = H2) O 2 steps
N N
or N
X O RO O O
NaBH4 H
(X = O) O
(101a) (X = H2) (102a) (R = Me, 50%) (103)
(101b) (X = O) (102b) (R = H, 80%)
Scheme 33 Anodic N-α-methoxylation en route to octahydroisoquinolines.

HO2C O O MeO2C O O
N OH N OMe
( )n ( )n
OH
Me Cl
(104a) (n = 1 A58365A) (105)
(104b) (n = 2 A58365B)
1. Anodic oxid
2. TiCl 4
R MeO2C O O
H
N N OMe
( )n ( )n
Me
(107) (106)
Scheme 34 Retrosynthesis of ACE inhibitors using an N-a-methoxylation as key step.
could be used to make the two molecules if proline derivative (109) (Scheme 35). The
a procedure was found for annulating the carbon alpha to the nitrogen was then func-
aromatic ring onto the starting amine. For tionalized using a carbon anode, a 0.03 M
A583655A, this was accomplished by first Et4 NOTs in methanol electrolyte solution,
converting prolinol into the substituted and an undivided cell. After 6.5 F mole−1 ,
HOH2C O 1. Me 3Al, benzene O O

MeO2C
reflux, 90%
NH + O N OMe
2. a. Jones oxid.
Me b. Me 2NCH(OMe)2
benzene, reflux Me
(108) (109) 41% (106)
Carbon anode
0.03 M Et4NOTs
MeOH
undivided cell
6.5 F mole−1
MeO2C O O MeO2C O O
N OMe 1. TiCl 4, CH2Cl2 N OMe

2. a. O 3, MeOH
b. Zn, HOAc OMe Me
O −78 °C to RT
(111) (72% (110) (83%,

from (110)) 6% recovered SM)
Scheme 35 Synthesis of an ACE inhibitor using an N-α-methoxylation as key step.

an 83% isolated yield of the methoxylated an anodic oxidation reaction to form

amide was obtained. Treatment of this the methoxylated carbamate (115) from
product with TiCl4 then afforded a cy- proline (Scheme 37). This transformation
clized product (105) that upon ozonolysis was done by protecting the acid as a
led to the formation of the bicyclic amide methyl ester, protecting the proline amine
derivative (111). The bicyclic amide was with a Cbz group, and then utilizing an
converted into A58365A in four steps. anodic amide oxidation to methoxylate
Using an identical process, the pipecolic the C5 position. The three-step procedure
acid derivative (112) was converted into led to a 69% overall yield of (115). The
a bicyclic amide derivative as shown in methoxylated amide was then treated with
Scheme 36. In this case, the methoxy- a cuprate reagent in the presence of
lated amide proved to be unstable in the BF3 • Et2 O in order to produce (116). As with
crude electrolysis reaction and was taken other cuprate additions to N -acyliminium
directly into the cyclization–ozonolysis se- ions, the stereochemistry obtained for the
quence. A 74% yield of the bicyclic ketone reactions placed the incoming nucleophile
was obtained over three steps. Compound trans to the methyl ester [72–74]. The
(114) was converted into A58365B demon- rationale for this stereochemistry is that
strating that the anodic oxidation reaction the methyl ester complexes a cuprate along
allowed for rapid access to both natu- with the pi-system of the iminium ion.
ral products. This effectively blocks the face of the
iminium ion that is syn to the methyl
10.5.4 ester (Fig. 1), and forces the nucleophile to
(3R, 5R, 8aR)-3-n-Butylindolizidine approach from the opposite face.
Once the functionalized proline (116)
The functionalization of proline has been was in place, it could be converted to
used to synthesize natural products from the desired indolizidine ring system using
the indolizidine alkaloid family [71]. To several steps, which included a Wacker
this end, Lhommet and coworkers utilized oxidation, to generate a methyl ketone
MeO2C O O Carbon anode MeO2C O O

0.03 M Et4NOTs
N OMe N OMe
MeOH
undivided cell
OMe
Me Me
(112) (113)
HO2C O O 1. TiCl 4, CH2Cl2

2. a. O 3, MeOH
N OH b. Zn, HOAc
O
(114) (74% from (112))
Scheme 36 Synthesis of an ACE inhibitor using an N-α-methoxylation as key step.

3 steps (two
N CO2H protections and MeO N CO2Me
an anodic oxid.)
H Cbz
(115)
( )3Cu
BF3 • Et2O, Et 2O
80%
H
Several steps
N ( )3 N CO2Me
Me Bu
Cbz
(117) (116)
Scheme 37 Synthesis of an indolizidine precursor using an N-α-methoxylation.
Fig. 1 Transition state for the O

cuprate addition. OMe
Cu
+
N
R
CuLi
( )n
and a subsequent intramolecular reductive oxidation was employed in the synthesis of

amination reaction. Bulgecin C (Scheme 38) [75]. In this work,
a 4-hydroxyproline derivative was func-
10.5.5 tionalized at C5 using the electrochemical
Bulgecin C methodology (Scheme 39). It was found
that both the group at the four-position of
Anodic oxidation reactions have also been the ring and the protecting group on the
used to functionalize substituted proline nitrogen had an impact on the oxidation
derivatives. For example, an anodic amide reaction. In the best case, the 4-hydroxy
OH
NaO3SO HO HO
HO O
O
N
H N CO2H N CO2H
Ac
CO2H OH
N
H H
OH
H
(118) (Bulgecin C) (119) (Bulgecinine) (120)
Scheme 38 Retrosynthesis of Bulgecinine.

AcO AcO
Carbon anode
Et4NOTs
N CO2Me MeOH, CH2Cl2 MeO CO2Me
N
5 F mole−1
SiMe3 SiMe3
O O O O
(121) (122) (66%)
Scheme 39 Anodic N-α-methoxylation as key step to a Bulgecinine precursor.
group was protected as an acetate and the the methoxycarbamate protected proline
nitrogen of the proline ring protected with (125) and the second to initiate the
a trimethylsilylcarboxy group. The anodic formation of the bridged bicyclic ring
oxidation reaction then afforded a 66% skeleton. In a reaction typical of anodic
isolated yield of the methoxylated product. amide oxidations, the second methoxyla-
The methoxylated product was converted tion reaction occurred regioselectively at
into bulgecinine (119) in five steps. the least-substituted carbon.
A similar series of reactions have been
studied by Thaning and Wistrand [73, 76].
In these experiments, the acetoyl-protected 10.6
proline derivatives were oxidized using The Synthesis of Constrained
Peptidomimetics
constant current conditions, a platinum
anode, tetrabutylammonium tetrafluorob- 10.6.1
orate as electrolyte, and a methanol solvent Introduction
(Scheme 40).
In many of the direct amide oxidations il-
10.5.6 lustrated above, the reactions were used to
(±)-Anatoxin A functionalize amino acid derivatives. Be-
cause of the reactions effectiveness in this
Shono and coworkers have used a pair area, anodic electrochemistry has proven
of amide oxidation reactions to syn- to be an outstanding tool for building
thesize the naturally occurring alka- constrained peptidomimetics [78–81]. In
loid Anatoxin A [77]. As illustrated in this work, a series of constrained pep-
Scheme 41, the synthesis used the first tide analogs were designed by replacing
anodic amide oxidation to functionalize spatially close hydrogens in a proposed
R1 R2 R1 R2
Carbon anode
Et4NOTs
N CO2Et MeOH, CH2Cl2 MeO CO2Et
N
5 F mole−1
O O
(123a) (R1 = H; R 2 = OAc) (124a) (60%)
(123b) (R1 = OAC; R 2 = H) (124b) (50%)
Scheme 40 Anodic N-α-methoxylation as key step to a Bulgecinine precursor.

10.6 The Synthesis of Constrained Peptidomimetics 303
Carbon anode CO2Et

const. current TiCl4, CH2Cl2
N N OMe
Undivided cell OTMS N
Et4NOTs, MeOH
CO2Me CO2Me OEt
CO2Me
(125) (126) (80%) (127) (100%)
Carbon anode
const. current
undivided cell
CO2Me Et4NOTs, MeOH
CO2Me
N O N CO2Et
5 steps TiCl4
Me CH2Cl2 MeO N
CO2Et
Cl CO2Me
(130) (Anatoxin A) (129) (70%) (128) (74%)
Scheme 41 A double N-α-methoxylation for the synthesis of the α,α -disubstituted proline: Anatoxin.
active peptide conformation with carbon- in the lab? The key is to recognize that
based bridges. This resulted in molecules such transformations require the selective
that fixed both the peptide backbone oxidation of the initial amino acid starting
conformation and the amino acid side material. Therefore, they are ideally suited
chains in place with a polycyclic ring skele- for use in anodic electrochemistry.
ton. Two such constrained analogs are
illustrated in Scheme 42. While analogs of 10.6.2
this nature are simple to design, they can The Synthesis of Constrained TRH Analogs
be difficult to synthesize. How does one
‘‘simply’’ replace spatially close hydrogens The thyrotropin-releasing hormone (TRH)
with carbon bridges in a real molecule is the hypothalamic tripeptide that releases
H H
O O
O O
N N
?
N N
R1 R2 R1 R2
H H ( )n
H
(131) (132)
O O
O O
?
R1 N R1 N
R2 R2
N H H N
H
H
(133) (134)
Scheme 42 Constrained peptidomimetics.

the thyroid-stimulating hormone from an anodic oxidation to functionalize a

the anterior pituitary gland [82, 83]. In pyroglutamate derivative.
addition to this endocrine behavior, TRH Both anodic oxidation reactions pro-
displays effects in the brain, blood, spinal ceeded well. As illustrated in Scheme 44,
cord, and gut. Because of its biological an anodic methoxylation of menthyl py-
relevance, a large effort has been made to roglutamate followed by the trapping of
probe conformation of TRH responsible an incipient N -acyliminium ion with allyl-
for binding to its endocrine receptor. As silane in the presence of Lewis acid led
part of this effort, the constrained analogs to (138) [86]. While the stereoselectivity
(136) of TRH illustrated in Scheme 43 of this reaction was not high, the major
were designed [84, 85]. The retrosynthesis product from the reaction could be frac-
of the constrained analogs called for the tionally crystallized from hexane and the
initial synthesis of two building blocks, route used to conveniently prepare (138)
each of which could be envisioned as on a scale of 10 g. In this case, a platinum
arising from an initial amino acid starting wire anode was used in order to keep the
material by the use of an anodic amide current density high. This was required be-
oxidation. The first building block (137) cause of the high oxidation potential of the
would be used to constrain the two right- secondary amide relative to the methanol
hand amino acids and would be made solvent used in the reaction.
by using an anodic amide oxidation to The anodic oxidation utilized in the
functionalize a proline derivative. The synthesis of (137) proved equally effec-
second building block (138) would be used tive. In this example, the electrochemical
to constrain the pyroglutamate portion of step was used to functionalize the amide
the ring and would be made by using substrate (141) (Scheme 45) [87, 88]. A
A
O O
H H
N N
H H
( )n
N O CONH2 O
N CONH2
O ? O
N N
HN R
H H ( )m
N Ha
B
(135) TRH (136)
H
O CO2Me
O N ( )n H2N
+ N
OR
R ( )m
O H
(138) (137)
Scheme 43 Retrosynthesis of constrained TRH analogs.

10.6 The Synthesis of Constrained Peptidomimetics 305
Pt wire anode
H and cathode OMe
nBu4PF6
N OR* N OR*
O MeOH O
H O const. current H O
26.8 mA/ 4.5 F
(139) (R* = menthyl) 95% (140)
TiCl4
allyl-TMS
CH2Cl2
−78 °C to RT
N OR*
O
H O
(2 : 1 ratio of diastereomers,
major isomer shown;
Isolated yield of the pure
R-isomer = 54%)
(138)
Scheme 44 Synthesis of a TRH analog building block by anodic N-α-methoxylation.
O O
CH2OBn CH2OBn
Carbon anode
N 0.3 M Et4NOTs N
MeOH
26.8 mA (2.1 F mole−1) OMe
74% (16% rec. SM)
(141) (142)
TiCl4
CH2Cl2
94%
O CH2OH
4 steps N
(137)
Cl H
(143)
Scheme 45 Synthesis of a TRH analog building block by anodic N-α-methoxylation.
74% isolated yield of the methoxy- with titanium tetrachloride and methy-
lated product was obtained along with lene chloride then led to a cycliza-
16% of the recovered starting material. tion – rearrangement sequence that gener-
Treatment of the methoxylated product ated the bicyclic amide (143). Intermediate
(143) was converted into the desired pep- analogs with stereocenters in the lactam
tide building block in four steps. Once ring. Second, the cyclization reaction to
the building blocks were available, the form (143) led to a mixture of stereoiso-
fully constrained analogs (136, n = m = 1) mers at the bridgehead carbon. For the
were synthesized in a straightforward fash- purpose of initially screening analogs this
ion [89]. was fine. Both isomers were desired. But
once a biological preference was found
10.6.3 for the isomer having an R-configuration
Sequential Amide Oxidation – Olefin at the bridgehead, a more selective route
Metathesis Strategies became highly desirable. Finally, the re-
arrangement reaction encountered during
While the sequence to synthesize (137) the synthesis of (143) rendered it diffi-
as outlined above proved effective for ob- cult to make seven-membered ring lactam
taining initial biological testing data on analogs. Such analogs were needed in or-
the analogs, it suffered from several major der to reintroduce a degree of flexibility
weaknesses. First, the oxidation reaction into the analogs.
did not allow the presence of either an oxy- In order to address these issues, a
gen or a nitrogen functional group on the strategy for effecting the anodic oxida-
carbon alpha to the amide carbonyl. The tion reaction earlier in the synthesis was
presence of such a group stopped the elec- designed. This plan called for functional-
trolysis, presumably because the oxidation izing a proline derivative and then using
potential of the substrate became higher the resulting methoxylated amide to in-
than the methanol solvent. The result was troduce a vinyl group to the carbon alpha
the need to functionalize the molecule late to the nitrogen (Scheme 46) [72–74]. The
in the synthesis following construction of resulting vinyl proline derivative would
the bicyclic ring skeleton. Such an ap- be coupled to a second vinyl-substituted
proach made it difficult to build bicyclic amino acid building block and an olefin
MeO2C CO2Me H CO2Me

N Ref. 65 N
MeO
(144) (145)
O
BocHN EDCI, HOBt
OH NEM, CH Cl
2 2
Ph 83%
O
BocHN CO2Me 1. Cl 2(PCy3)2Ru = CHPh O
CH2Cl2, 65% BocHN CO2Me
N (24% rec. SM)
Ph N
2. 5% Pd on C Ph
H2, MeOH
(147) (146)
Scheme 46 Sequential amide oxidation–olefin metathesis strategy.

10.7 Amide Oxidations and the Construction of Combinatorial Libraries 307
metathesis reaction used to complete the been utilized to synthesize the second
synthesis of the building block [90–93]. In family of analogs illustrated in Scheme 42
the synthesis illustrated, methyl proline (134) [99, 100]. Analogs of this family were
was protected as a carbamate and then oxi- designed as mimics for the Phe7 Phe8 re-
dized at an anode to form starting material gion of substance P [101–104]. In this
(144). This starting material was converted work, an anodic oxidation of the known
into a vinyl-substituted amino acid deriva- 3-phenyl-substituted proline [105] methyl
tive (145) [94–96] that was then coupled ester led to a methoxylated amide (149)
to a known carboxylic acid [97] in order that was treated with a cuprate reagent, de-
to form diene (146). Olefin metathesis fol- protected, and coupled to a Cbz-protected
lowed by hydrogenation of the double bond phenylalanine in order to afford (150)
resulted in the synthesis of the desired (Scheme 47). Ozonolysis and a reductive
building block (147). This route proved amination reaction led to the formation
very effective and has now been used to of a bicyclic derivative that was subse-
synthesize a series of constrained TRH quently converted into a building block
analogs [98]. for solid-phase peptide synthesis (151) by
reprotecting the nitrogen with a t-Boc
10.6.4 group and saponifying the methyl ester
Substance P Analogs and an Approach to with lithium hydroxide.
Piperazinone Rings
The use of an anodic amide oxidation to 10.7

introduce a vinyl group to the C5 posi- Amide Oxidations and the Construction of
tion of a proline derivative has proven to Combinatorial Libraries
be an effective strategy for building other
constrained peptidomimetics as well. For In addition to demonstrating the utility
example, a variation on the approach has of anodic amide oxidations as a tool for
CO2Me Carbon anode Boc CO2Me

Boc
Et4NOTs/ MeOH
N N
Ph 26.8 mA Ph
3.0 F mole−1 MeO
(148) 87% (149)
1. CH 3CH = CHLi, CuBr • Me2S
BF3 • Et2O, −78 °C to 0 °C
75%
2. BF 3 • Et2O, Et 2O, RT
3. Cbz-Phe-F, NEM
CH2Cl2, 60%
1.a) O3, MeOH, −78 °C
O CO2H b) Me2S, RT, 84%
2. H 2, Pd on BaSO4 O CO2Me
Ph N
Ph MeOH, 75%
N Ph N
3. Boc 2O, NEM, 83% Ph
Boc NH
4. LiOH, THF/MeOH Cbz
(151) H2O, 60% (150)
Scheme 47 Piperazinone ring by N-α-methoxylation of a proline derivative.

constructing complex natural products and ion was regenerated in the presence of
peptidomimetics, recent work has been the nucleophile with the use of an acid.
focusing on developing the reaction as a With the use of the cation pool method,
tool for synthesizing libraries of molecules. both, the need for methanol trapping and
Yoshida and coworkers have recently the need for regenerating the iminium ion
reported that anodic amide oxidation with a Lewis acid can be avoided. The
can be used to make a stable ‘‘cation oxidation reaction is conducted at a low
pool’’ of iminium ions (Scheme 48) [106]. temperature using dichloromethane as the
Once generated, the cation pool was solvent. No nucleophile is present. Under
directly trapped with nucleophiles in these conditions, the N -acyliminium ion
order to generate new carbon–carbon is stable; even to temperatures up to zero
bonds. This development was interesting degrees. Adding the nucleophile to the
because it has the potential to overcome cation pool then completes the reaction.
many of the synthetic problems that Allylsilanes, 1,3-dicarbonyl equivalents,
can complicate the direct trapping of and electron-rich aromatic rings have all
oxidatively generated electrophiles with been used as nucleophiles for this process.
nucleophiles. Since cationic intermediates Recently, Yoshida and coworkers demo-
are generally not stable in oxidation nstrated that the cation pool method can
conditions, the nucleophile for such a be used to make available N -acyliminium
reaction normally needs to be present ion intermediates for parallel synthesis
during the oxidation so that it can trap approaches to molecular libraries [106]. In
the electrophile as it is generated. This this work, the cation pool was split into
creates problems since most nucleophiles separate flasks following the electrolysis
are also sensitive to oxidation. For example, reaction. Different nucleophiles were then
an allylsilane oxidizes at a potential added to each flask in order to form a series
lower than that of an amide. Therefore, of products (Scheme 49).
the oxidative generation of an iminium Direct electrochemical amide oxidation
ion in the presence of an allylsilane reactions have also been employed in
nucleophile is not possible. It was for parallel synthesis using a spatially ad-
this reason that the amide oxidations, dressable electrochemical platform [107].
described in the sections above, were In this work, an electrolysis platform was
normally done in a methanol solvent. The set up so that 16 electrochemical reactions
solvent trapped the iminium ion affording could be run in parallel at the same time.
an N -α-alkoxyamide product that was The cells were set up in a 4 by 4 array
isolated. In the second step, the iminium in which each cell was equipped with a
Carbon anode
Bu4NClO4 Nuc-H or
N CH2Cl2, −74 °C N+ Nuc-TMS Nuc

N
O OMe O OMe O OMe
(152) (153) (Stable pool of cations) (154)
Scheme 48 Cation pool method for N-α-substitution.

10.8 Conclusions 309
Split the
(153) (153) (153) (153) (153) …
pool
Nuc1 Nuc2 Nuc3 Nuc4
N Nuc1 Nuc2 Nuc3 N Nuc4

N N
CO2Me CO2Me CO2Me CO2Me
Scheme 49 Parallel synthesis for N-α-substituted proline derivatives.
stainless steel cathode and a graphite rod trapping the incipient N -acyliminium with
anode. The cathodes were welded into a an intramolecular alcohol nucleophile gen-
stainless steel plate that then served as erated a small library of bicyclic amide
a common terminal for the connection products (Scheme 50). The intramolecular
to the current source. The graphite elec- reactions proceeded in yields of 80 to 95%.
trodes served as the working electrodes
and were isolated from each other and
the cathodes with the use of a Teflon 10.8
plate. The 16 anodes were then connected Conclusions
in a parallel circuit so that a constant
current reaction could be performed in The anodic oxidation of nitrogen com-
each cell. In a typical experiment, one of pounds provides an excellent example of
four carbamates was added to each cell how the use of electrochemistry can alter
along with one of four different alcohols. the way in which we view the syntheses
The reaction cells were charged with a of complex organic molecules. Currently,
0.5 M Bu4 NBF4 in 1 : 1 acetonitrile/alcohol there are two main thrusts to these efforts.
electrolyte solution, and then a con- First, the oxidation reactions allow for a
stant current applied until 2.0 F mole−1 reversal in the polarity of known func-
of electricity had been passed through tional groups, and therefore molecules
each cell. The reactions afforded the 16 with nucleophilic nitrogens can be con-
N -α-alkoxyamides in yields that ranged verted into electrophiles. Second, the ox-
from 61 to 95%. In another experiment, idation reactions allow for the selective
O
( )n
N O N O
O ( )m R O ( )m R
(155) n = 2, m = 2, R = H (156) n = 2, R = H
n = 2, m = 1, R = Me n = 1, R = Me
n = 1, m = 2, R = H
n = 1, m = 1, R = Me
Scheme 50 Electrogenerated library of bicyclic amides.

functionalization of amine and amino acid 8317. Slightly more sophisticated prepar-
starting materials. The addition of func- ative electrolysis setups can be obtained
from The Electrosynthesis Co., Inc, 72 Ward
tionality to these molecules enables their
Road, Lancaster, NY 14086-9779.
use as building blocks for constructing a 6. For a very brief ‘‘synthetic chemists’’
variety of more complex structures. The re- discussion of basics see K. D. Moeller,
sult has been the simplified construction of Tetrahedron 2000, 58, 9527.
synthetically useful chiral starting materi- 7. For a pair of excellent discussions of
electrochemical principles see H. Lund,
als, biologically relevant natural products,
O. Hammerich, Eds., Organic Electrochem-
and conformationally constrained pep- istry: An Introduction and a Guide, 4th ed.,
tidomimetics. Marcel Dekker, New York, 2001.
Finally, it is important to note that 8. A. J. Fry, Synthetic Organic Electrochemistry,
many of the anodic reactions discussed 2nd ed., John Wiley & Sons, New York,
above cannot be duplicated with traditional 1989.
9. E. Steckhan, Top. Curr. Chem. 1987, 142, 1.
chemical oxidants. For this reason, the 10. U. Bornewasser, E. Steckhan in Electroor-
anodic oxidation of nitrogen-containing ganic Synthesis: Festschrift for Manuel
compounds represents a powerful class of M. Baizer (Eds.: R. D. Little, N. L. Wein-
reactions that has the potential to open berg), Marcel Dekker, New York, 1991,
up entirely new synthetic pathways to pp. 205–215.
11. T. Inokuchi, L. Ping, F. Hamaue et al.,
complex molecules. From the work already Chem. Lett. 1994, 121.
accomplished, it is clear that employing 12. M. F. Semmelhack, C. R. Schmidt, J. Am.
such an approach is both feasible and Chem. Soc. 1983, 105, 6732.
beneficial, and that the ability to selectively 13. Y. Kashiwagi, F. Kurashima, C. Kikuchi
oxidize amines and amides is a valuable et al., Heterocycles 2000, 53, 1583.
14. T. Shono, Y. Matumura, K. Inoue, J. Am.
‘‘tool’’ for any synthetic chemist to have at Chem. Soc. 1984, 106, 6075.
their disposal. 15. Y. Kashiwagi, F. Kurashima, C. Kikuchi
et al., J. Chem. Soc., Chem. Commun. 1999,
1983.
Acknowledgment
16. A. Konno, T. Fuchigami, Y. Fujita et al., J.
Org. Chem. 1990, 55, 1952.
This chapter is dedicated to the mem- 17. T. Fuchigami, Y. Nakagawa, T. Nonaka, J.
ory of Professor Eberhard Steckhan Org. Chem. 1987, 52, 5489.
(9/12/43–2/10/2000). 18. F. Billon-Souquet, T. Martens, J. Royer,
Tetrahedron Lett. 1999, 40, 3731.
19. For general discussions of electroauxiliaries
References and their application to the oxidation of
ethers see: J. Yoshida, J. Syn. Org. Chem.
1. For reviews of reductive routes to N- Jpn. 1995, 53, 53.
acyliminium ion formation see H. E. Za- 20. J. Yoshida, M. Sugawara, N. Kise, Tetrahe-
ugg, Synthesis 1984, 85, 181. dron 1996, 37, 3157.
2. W. N. Speckamp, H. Hiemstra, Tetrahedron 21. M. Sugawara, K. Mori, J. Yoshida, Elec-
1985, 41, 4367. trochim. Acta 1997, 42, 1995.
3. W. N. Speckamp, Recl. Trav. Chem. Pays- 22. S. Yamago, K. Kokubo, J. Yoshida, Chem.
Bas 1981, 100, 345. Lett. 1997, 111.
4. For a review of chemical oxidations of 23. J. Yoshida, M. Watanabe, H. Toshioka et al.
amines and some amides see S.-I. Mura- in Novel Trends in Electroorganic Synthe-
hashi, Angew. Chem., Int. Ed. Engl. 1995, 34, sis (Ed.: S. Torii), Springer-Verlag, Tokyo,
2443. 1998, pp. 99–102.
5. See for example: D. A. Frey, N. Wu, 24. J. Yoshida, T. Maekawa, T. Murata et al., J.
K. D. Moeller, Tetrahedron Lett. 1996, 37, Am. Chem. Soc. 1990, 112, 1962.
10.8 Conclusions 311
25. J. Yoshida, M. Sugawara, M. Tatsumi et al., 50. Y. Matsumura, Y. Takeshima, H. Okita,

J. Org. Chem. 1998, 63, 5950. Bull. Chem. Soc. Jpn. 1994, 67, 304.
26. J. Yoshida, T. Ishichi, S. Isoe, J. Am. Chem. 51. Y. Matsumura, T. Ohishi, C. Sonoda et al.,
Soc. 1992, 114, 7594. Tetrahedron 1997, 53, 4579.
27. J. Yoshida, K. Takada, Y. Ishichi et al. in 52. K. Danielmeier, K. Schierle, E. Steckhan,
Novel Trends in Electroorganic Synthesis Tetrahedron 1996, 52, 9743.
(Ed.: S. Torii), Kodansha, Tokyo, 1995, 53. M. Lennartz, M. Sadakane, E. Steckhan,
pp. 295–298. Tetrahedron 1999, 55, 14 407.
28. J. Yoshida, M. Watanabe, H. Toshioka et al., 54. K. Schierle, R. Vahle, E. Steckhan, Eur. J.
Chem. Lett. 1998, 1011. Org. Chem. 1998, 509.
29. E. Le Gall, J.-P. Hurvois, S. Sinbandhit, Eur. 55. M. Lennartz, E. Steckhan, Synlett 2000, 319.
J. Org. Chem. 1999, 2645. 56. N. Kise, H. Yamazaki, T. Mabuchi et al.,
30. M. Tokuda, T. Miyamoto, H. Fujita et al., Tetrahedron Lett. 1994, 35, 1561.
Tetrahedron 1991, 47, 747. 57. Y. Matsumura, Y. Kanda, K. Shirai et al.,
31. M. Tokuda, H. Fujita, T. Miyamoto et al., Org. Lett. 1999, 1, 175.
Tetrahedron 1993, 49, 2413. 58. A. Papadopoulos, B. Lewal, E. Steckhan
32. S. Karady, E. G. Corley, N. L. Abramson et al., Tetrahedron 1991, 47, 563.
et al., Tetrahedron 1991, 47, 757. 59. T. Shono, Y. Matsumura, S. Katoh et al., J.
33. G. M. Abou-Elenien, B. E. El-Anadouli, Am. Chem. Soc. 1990, 112, 2368.
R. M. Baraka, J. Chem. Soc., Perkin Trans. 2 60. J. Yoshida, S. Isoe, Tetrahedron Lett. 1987,
1991, 1377. 28, 6621.
34. T. Peglow, S. Blechert, E. Steckhan, Chem. 61. A. Oku, T. Kamada, J. Chem. Soc., Perkin
Eur. J. 1998, 4, 107. Trans. 1 1998, 3381.
35. For reviews see: N. L. Bauld, Tetrahedron
62. W. Li, C. E. Hanau, A. d’Avignon et al., J.
1989, 45, 5307.
Org. Chem. 1995, 60, 8155.
36. N. L. Bauld, D. J. Bellville, B. Garirchian
63. T. Fuchigami in Novel Trends in Electroor-
et al., Acc. Chem. Res. 1987, 20, 371.
ganic Synthesis (Ed.: S. Torii), Springer-
37. T. Shono, M. Chuankamnerdkarn, G. Mae-
Verlag, Tokyo, 1998, pp. 115–118.
kawa et al., Synthesis 1994, 895.
64. T. Fuchigami in Novel Trends in Electroor-
38. For a review see: H. J. Schäfer, Top. Curr.
ganic Synthesis (Ed.: S. Torii), Springer-
Chem. 1990, 152, 91.
39. M. Mori, K. Kagechika, H. Sasai et al., Verlag, Tokyo, 1998, pp. 129–130.
Tetrahedron 1991, 47, 531. 65. G. Butora, J. W. Reed, T. Hudlicky et al., J.
40. K. Danielmeier, D. Kolter, M. Sadakane Am. Chem. Soc. 1997, 119, 7694.
et al. in Novel Trends in Electroorganic Syn- 66. M. A. Endoma, G. Butora, C. D. Claeboe
thesis (Ed.: S. Torii), Springer-Verlag, Tokyo, et al., Tetrahedron Lett. 1997, 38, 8833.
1998, pp. 55–60. 67. T. Shono, Y. Matsumura, K. Tsubata, J. Am.
41. G. Kardassis, P. Brungs, E. Steckhan, Tetra- Chem. Soc. 1981, 103, 1172.
hedron 1998, 54, 3471. 68. K. D. Moeller, S. L. Rothfus, P. L. Wong,
42. D. Seebach, R. Charczuk, C. Gerber et al., Tetrahedron 1991, 47, 583.
Helv. Chim. Acta 1989, 72, 401. 69. K. D. Moeller, P. W. Wang, S. Tarazi et al.,
43. P. Renaud, D. Seebach, Angew. Chem., Int. J. Org. Chem. 1991, 56, 1058.
Ed. Engl. 1986, 25, 843. 70. P. L. Wong, K. D. Moeller, J. Am. Chem.
44. S. D. Ross, M. Finkelstein, C. Peterson, J. Soc. 1993, 115, 11 434.
Am. Chem. Soc. 1964, 86, 4139. 71. C. Célimène, H. Dhimane, M. Le Bail et al.,
45. S. D. Ross, M. Finkelstein, C. Peterson, J. Tetrahedron Lett. 1994, 35, 6105.
Org. Chem. 1966, 31, 128. 72. L.-G. Wistrand, M. Skrinjar, Tetrahedron
46. S. D. Ross, M. Finkelstein, C. Peterson, J. 1991, 47, 573.
Am. Chem. Soc. 1966, 88, 4657. 73. M. Thaning, L.-G. Wistrand, Acta Chem.
47. T. Shono, Top. Curr. Chem. 1988, 148, 131. Scand. 1992, 46, 194.
48. J. S. Swenton, T. N. Biggs, W. M. Clark, J. 74. I. Collado, J. Ezquerra, C. Pedregal, J. Org.
Org. Chem. 1993, 58, 5607. Chem. 1995, 60, 5011.
49. M. C. Carreño, M. Ribagorda, J. Org. Chem. 75. A. G. M. Barrett, D. Pilipauskas, J. Org.
2000, 65, 1231. Chem. 1991, 56, 2787.
76. M. Thaning, L.-G. Wistrand, Helv. Chim. 90. For the initial paper describing the appli-
Acta 1986, 69, 1711. cation of RCM reactions to the synthe-
77. T. Shono, Y. Matsumura, K. Uchida et al., sis of a peptidomimetic see S. J. Miller,
Chem. Lett. 1987, 919. R. H. Grubbs, J. Am. Chem. Soc. 1995, 117,
78. For a review concerning the use of 5855. For reviews of RCM reactions see.
lactam based constrained peptidomimetics 91. R. H. Grubbs, S. J. Miller, G. C. Fu, Acc.
see: S. Hanessian, G. McNaughton-Smith, Chem. Res. 1995, 28, 446.
H.-G. Lombart et al., Tetrahedron 1997, 53, 92. S. Blechert, M. Schuster, Angew. Chem., Int.
12 789. For more recent references see: Ed. 1997, 36, 2036. For a route to a fused
79. F. Polyak, W. D. Lubell, J. Org. Chem. 1998, heterocycle see.
63, 5937. 93. S. F. Martin, Y. Liao, H. J. Chen et al., Tetra-
80. T. P. Curran, L. A. Marcaurell, K. M. hedron Lett. 1994, 35, 6005.
O’Sullivan, Org. Lett. 1999, 1, 1998. 94. J.-M. Manfre, F. Kern, J.-F. Biellmann, J.
81. F. Gosselin, W. D. Lubell, J. Org. Chem. Org. Chem. 1992, 57, 2060.
2000, 65, 2163. 95. L. M. Beal, K. D. Moeller, Tetrahedron Lett.
82. For reviews on the biology of TRH 1998, 39 4639.
see: ‘‘Thyrotropin-Releasing Hormone: Bio- 96. J. A. Campbell, H. Rapoport, J. Org. Chem.
medical Significance’’ G. L. Metcalf Olson, 1996, 61, 6313.
H. C. Cheung, M. E. Voss et al., Eds., Pro- 97. U. Kazmaier, A. Krebs, Angew. Chem., Int.
ceedings of the Biotech USA ’89 Meeting, San Ed. Engl. 1995, 34, 2012.
Francisco, October 1989. 98. L. M. Beal, B. Liu, W. Chu et al., Tetrahe-
83. J. Coa, D. O’Donnell, H. Vu et al., J. Biol. dron 2000, 56, 10 113.
Chem. 1998, 273, 32 281. 99. Y. Tong, Y. M. Fobian, M. Wu et al., J. Org.
84. For work leading to 136 as a proposed Chem. 2000, 65, 2484.
endocrine receptor bound conformation 100. Y. M. Fobian, K. D. Moeller, Methods in
of TRH see: G. R. Marshall, F. A. Gorin, Molecular Medicine, Peptidomimetics Pro-
M. L. Moore in Annual Reports in Medic- tocols (Ed.: W. M. Kazmierski), Humana
inal Chemistry ( Ed.: F. H. Clarke), Aca- Press, Totowa, NJ, 1999, Vol. 23, p. 259.
demic Press, New York, 1978, Vol. 13, 101. D. G. Payan, Annu. Rev. Med. 1989, 40, 341.
pp. 227–238. 102. M. Ichinose, N. Nakajima, T. Takahashi
85. J. Font, Ph.D. Thesis, Washington Univer- et al., Lancet 1992, 340, 1248.
sity, St. Louis, 1986. 103. C. A. Maggi, R. Patacchini, P. Roverro et al.,
86. L. D. Rutledge, J. H. Perlman, M. C. J. Auton. Pharmacol. 1993, 13, 23.
Gershengorn et al., J. Med. Chem. 1996, 39, 104. M. S. Dramer et al., Science 1998, 281, 1640.
1571. 105. J. Y. L. Chung, J. T. Wasicak, W. A. Arnold
87. W. Li, K. D. Moeller, J. Am. Chem. Soc. 1996, et al., J. Org. Chem. 1990, 55, 270.
118, 10 106. 106. J. Yoshida, S. Suga, S. Suzuki et al., J. Am.
88. L. Laakkonen, W. Li, J. H. Perlman et al., Chem. Soc. 1999, 121, 9546.
Mol. Pharmacol. 1996, 49, 1092. 107. T. Siu, W. Li, A. K. Yudin, J. Comb. Chem.
89. W. Chu, J. H. Perlman, M. C. Gershengorn 2000, 2, 545.
et al., Bioorg. Med. Chem. Lett. 1998, 8, 3093.
313
11
Electrosynthesis of Natural
Products, Fine Chemicals, and
Pharmaceuticals
R. Daniel Little
University of California, Santa Barbara, California
11.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
11.2 Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316

11.2.1 Electrohydrocyclization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
11.2.2 Electroreductive Cyclization . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317
11.2.3 Reductive Cyclization of Ketonitriles . . . . . . . . . . . . . . . . . . . . . . 319
11.2.4 Reductive Cyclization of Pyridinium Salts . . . . . . . . . . . . . . . . . . 319
11.2.5 Vitamin B12 -mediated Cyclizations . . . . . . . . . . . . . . . . . . . . . . . 321
11.2.6 Organonickel and Organopalladium Reagents . . . . . . . . . . . . . . . 322
11.3 Oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324

11.3.1 Kolbe Oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
11.3.2 Arene Oxidations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
11.3.3 [5 + 2] Cycloadditions to Oxidized Aromatics . . . . . . . . . . . . . . . . 327
11.3.4 Oxidation at and Adjacent to Nitrogen . . . . . . . . . . . . . . . . . . . . . 331
11.4 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336

Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336
315
11.1 a reduction or an oxidation is being in-

Introduction vestigated. Controlled potential methods
allow one to set the potential to a value
The utility of the electrode to promote bond corresponding to that of the electrophore
formation between functional groups of (the unit undergoing redox chemistry), in
the same polarity provides researchers much the same way that a light filter
with an opportunity to explore the chem- allows one to selectively irradiate a par-
istry of interesting intermediates, and ticular chromophore in a photochemical
synthetic strategies that are based on their process. Just as one should record an ul-
intermediacy [1, 2]. Reduction at a cathode, traviolet (UV) spectrum to determine the
or oxidation at an anode, renders electron- appropriate filter prior to conducting a
poor sites rich, and electron-rich sites, photolysis, one ought to obtain the anal-
poor. For example, the reduction of an α, β- ogous cyclic voltammogram (CV) of the
unsaturated ketone leads to a radical anion material to be studied electrochemically.
in which the β-carbon possesses nucle- The voltammogram describes how the cur-
ophilic, rather than electrophilic character. rent changes as a function of potential and
Similarly, oxidation of an enol ether affords allows one, therefore, to select the poten-
a radical cation wherein the β-carbon dis- tial best suited to the redox transformation
plays electrophilic, rather than its usual of interest.
nucleophilic behavior [3]. The following presentation focuses upon
Electrochemical processes are con- redox processes that lead to the production
ducted under what one refers to as either of natural products, fine chemicals, and
‘‘constant current’’ (CC) or ‘‘controlled po- pharmaceuticals. Rather than providing an
tential’’ (CP) conditions [1, 2]. The constant exhaustive coverage of the literature, our
current electrolysis (CCE) is often pre- intent is to provide the reader with the
ferred; it is less expensive to implement general flavor of the transformations that
since it does not require the acquisition can be conducted as well as their utility
of a potentiometer, is readily amenable within the context of organic synthesis.
to scale-up, and reaction times are often Our coverage merely skims the surface of
short. The disadvantage is that in or- this rich and fertile area of investigation.
der to maintain a constant current, the Excellent treatises and reviews exist, and
potential changes, become more nega- the interested reader is referred to them
tive or positive, depending on whether for greater detail [1–12].
316 11 Electrosynthesis of Natural Products, Fine Chemicals, and Pharmaceuticals
11.2 rings, but not for rings of sizes seven and

Reduction eight [13, 14].
The utility of the electrohydrocyclization
As indicated, the reduction of an electron- reaction to assemble natural products
deficient alkene renders a formally elec- remains essentially untapped. It has,
tropositive carbon center nucleophilic. however, been used in the synthesis of
The fields of electrohydrodimerization and the tricyclic sesquiterpene 1-sterpurene
electrohydrocyclization are a direct con- (3), the presumed causative agent of
sequence of this realization [1, 2]. The the so-called ‘‘silver leaf disease’’ that
former corresponds to the dimerization effects certain species of scrubs and trees
of an electron-deficient alkene via a pro- in Western North America [15]. As is
cess that couples the electron-deficient illustrated in Scheme 1 and in Table 2,
β-carbons of the substrate. Overall, two the electrohydrocyclization reaction of
electrons and two protons are consumed. bisenoate (5) was used to create the five-
Electrohydrocyclization is the intramolec- membered ring of the natural product.
ular counterpart of this process. The reaction was investigated under a
variety of conditions. As noted in Table 2,
11.2.1 both the yield and stereo-selectivity varied
Electrohydrocyclization in response to changes in the electrode
and proton donor (HD). Environmental
This transformation is undoubtedly the factors clearly make the use of a glassy
best-known cathodically initiated cycliza- carbon electrode preferable to mercury or
tion. Substrates consist of two electron lead electrodes. Yields range from 58 to
deficient alkenes tethered to one another. 87%, and the stereo-selectivity from a low
As illustrated in Table 1, the methodology of 2.6 : 1 trans/cis (6a/6b) to as high as
is exceptionally useful for the construc- 14.8 : 1 when the reaction is conducted in
tion of three-, five-, and six-membered the presence of cerium (III) chloride.
Tab. 1 Ring sizes accessible using electrohydrocyclization

b
CH CHX CH2X
−1.8 to −2.1 V (Hg; SCE)
(R2C)n (R2C)n
Et4NOTs, CH 3CN/H2O
CH CHX CH2X
b′
(1) (2)
n Ring size R X Yield (%)
1 3 Et CO2 Et 98
2 4 H CO2 Et 41
2 4 H CN 15
3 5 H CO2 Et ∼quant
4 6 H CO2 Et 90
5 7 H CO2 Et ∼10
6 8 H CO2 Et 0
11.2 Reduction 317
H
CO2CH3 2e
CO2CH3
CO2CH3 2HD CO2CH3

H
(4) (5)
(3), 1-sterpurene
Scheme 1 Electrohydrocyclization en route to 1-sterpurene.
Tab. 2 Effect of proton donor and electrode material
CO2CH3 +2e, +2HD CO2CH3

CO2CH3 R4NX CO2CH3
(5) (6a) (trans), (6b) (cis)
Electrode Proton source trans/cis ratio Yield (%) Additive
Hg AcOH, H2 O 2.6 : 1 82–87 none

Hg CH2 (CO2 Et)2 7.5 : 1 66 none
Glassy carbon CH2 (CO2 Et)2 7.1 : 1 73 none
Cu CH2 (CO2 Et)2 11.6 : 1 58 none
Hg CH2 (CO2 Et)2 14.8 : 1 73 CeCl3
11.2.2 Like the electrohydrodimerization and

Electroreductive Cyclization electrohydrocyclization reactions, this pro-
cess also requires the consumption of two
Many reductive cyclizations, including electrons and two protons. It has been
many of those that are not initi- shown to occur via a sequence consisting
ated electrochemically, correspond to of electron transfer followed by a rate-
variations on the electrohydrocyclization determining protonation of the resulting
theme. The so-called electroreductive- radical anion, addition of a second electron
cyclization reaction, for example, involves to generate a carbanion, cyclization of the
cyclization between the β-carbon of an carbanion onto the carbonyl acceptor unit
electron-deficient alkene and an alde- and the addition of the second proton [16].
hyde or ketone tethered to it, to form Carbon acids like dimethyl malonate and
a new σ -bond between these formally malononitrile are often used as a pro-
electron deficient centers (Scheme 2). ton source. The course of this and other
OH
G 2e, 2HD
(H2C) n (when G = COR′) R′
C(R)EWG (H2C)n
EWG = CO2R, COR, CN, etc. CH(R)EWG
(7) G = COR′, CH CREWG (8)
HD = proton donor
Scheme 2 General reaction of an electroreductive cyclization.

electrochemical reactions is conveniently and lactone (11) in a combined yield of

monitored using a variety of standard 89% (Scheme 3).
techniques including coulometry. The Adducts (10) and (11) were each con-
latter provides a straightforward means of verted to the unsaturated nitrile (12) that
determining when the theoretical amount is shown in Scheme 4. Electroreductive
of charge has been consumed. For each of cyclization of (12) presented a major
the reactions discussed thus far, this cor- challenge given the highly hindered na-
responds to 2 Faradays of charge per mol ture of the fully substituted β-carbon of
of substrate. the α, β-unsaturated subunit. Many or-
A demonstration of the utility of the ganic transformations fail to occur when
electroreductive cyclization reaction is presented with a similarly crowded envi-
provided by the formal total synthesis ronment. Thus, it is significant that the
of the antitumor agent quadrone (16, controlled potential electroreductive cy-
Scheme 4) [17]. The first stage of the clization reaction of (12) afforded a 90%
synthesis involved a controlled potential isolated yield of the requisite [3.2.1] adduct
reduction of (9) in the presence of (13). Steric factors clearly did not hinder
dimethyl malonate as the proton donor. this reaction, a result that is presumed
An efficient cyclization ensued, leading to to be generalizable to other electrore-
the formation of the γ -hydroxy ester (10) ductive cyclizations. Cycloadduct (13) was
O
CO2CH3 OH O
O
+2e, CH2(CO2Me)2
CO2CH3
n-Bu4NBr, CH 3CN
(89%)
(9) (10) (11)
Scheme 3 Electroreductive cyclization to γ -hydroxyester and a lactone.
NC NC OH
−2.4 V, CH 2(CO2Me)2
CH2OP
(CH2)2OSiPh2Bu-t
n-Bu4NBr, CH 3CN
(90%)
CHO
(12) (13), P = SiPh2Bu-t
O O
O
O CN
HO CH2OP
(16), quadrone (15) (14)
Scheme 4 Steric factors do not prohibit electroreductive cyclization.

11.2 Reduction 319
subsequently converted to enone (15) [18], the most effective. Using it, for example,
a point that converged with an existing allowed the controlled potential reduction
synthesis of quadrone (16). of (17) to proceed in a respectable 76%
yield. As illustrated in Table 3, the prefer-
11.2.3 ence for ketol formation drops when car-
Reductive Cyclization of Ketonitriles ried out at constant current or without us-
ing a diaphragm to separate the anode and
Ketones tethered to nitriles also function
cathode chambers of the electrolysis cell.
admirably as substrates in reductive cy-
The transformation has been employed
clizations [19, 20]. As illustrated by the
extensively in the preparation of precur-
example portrayed in the equation in
sors to a number of natural products
Table 3, reduction leads to the formation of
including dihydrojasmone, rosaprostol,
an α-ketol (18) as the major product. That
valeranone, and hirsutene [20]. Its use en
this functionality is present in many natu-
route to guaiazulene (23) is illustrated in
ral products and that it can be constructed
Scheme 5.
by coupling two very common functional
groups, adds interest to the transforma- 11.2.4
tion [21]. Both controlled potential and Reductive Cyclization of Pyridinium Salts
constant current conditions have been uti-
lized. Of the electrodes examined (Ag, Cd, Pyridinium salts tethered to ketones also
Pb, Zn, C-fiber, and Sn), tin was generally undergo reductive cyclization (Schemes 6
Tab. 3 Reductive cyclization of ketonitriles
O
O OH O
+e
i-PrOH
CN
(17) (18) (19)
Conditions F mol−1 Yield (% 18, % 19)
i-PrOH, 25 ◦ C, −2.8 V (SCE; Sn) divided cell, ceramic diaphragm 3 76, 2

i-PrOH, 25 ◦ C, constant current of 0.2 A, divided cell, ceramic 3.5 63, 16
diaphragm
i-PrOH, 25 ◦ C, −2.8 V (SCE; Sn) divided cell, no diaphragm 4 65, 11
O
CN R O
+e, i-PrOH
(3.4/1 21/22)
(75%)
(21), R = OH
(20) (23), guaiazulene
(22), R = H
Scheme 5 Reductive cyclization of ketonitriles an route to guaiazulene.

4e, 3H+ H H
OH + OH
N COCH3 (58%, 1.3 : 1 25 : 26) N N
(24) (25) (26)
Scheme 6 Reductive cyclization of an oxoalkyl pyridinium salt to a quinolizidine.
t-Bu t-Bu
4e, 3H+ H
N (58%) N OH
O O
(27) (28)
Scheme 7 Reductive cyclization of an oxoalkyl pyridinium salt to an indolizidine.
H H
O 4e, 3H+ OH OH
N (46%, >20 : 1 30 : 31) N + N
H H H
(29) (30) (31)
Hg (constant current of 4.2 mA cm−2, charge 8 F mol−1), 10% H2SO4,
0.2 M in pyridinium salt, 20 °C)
Scheme 8 Reductive cyclization of an oxoalkyl pyridinium salt to a quinolizidine.
to 8) [22]. The reaction provides a conve- electrode material as a reaction parameter

nient, diastereo-selective route to quino- that may need to be adjusted in order to
lizidine derivatives such as (25, 26, 30), determine optimal reaction conditions in
and (31), as well as to indolizidine deriva- an electrochemical transformation. To the
tives, (28). In each instance, the product inexperienced practitioner, this may seem
corresponds to that diastereomer wherein like an undesirable burden. One should
the hydroxyl group and ring junction hy- pause, however, to reflect upon the many
drogen are trans to one another. The experimental parameters that require ad-
transformation holds significant promise justment in experiments that do not use
as a route to alkaloids. A mercury cath- electrochemistry. With experience, one be-
ode is preferred; passivation occurs when comes as comfortable with having to spend
lead is used. Interestingly, the reaction a bit of time selecting the most useful elec-
does not occur using either graphite or trode as one does with having to vary other
glassy carbon electrodes. This observation reaction parameters in an effort to achieve
points out the need to treat the choice of optimization.
11.2 Reduction 321
11.2.5 (33), and ultimately to the California red

Vitamin B12 -mediated Cyclizations scale pheromone (34) [23].
Another illustration of the utility of this
Vitamin B12 reacts with alkyl halides to chemistry is provided by its use as the
form a cobalt (III) alkyl intermediate. key step in a synthesis of prostaglandin
Irradiation with visible light leads to the PGF2α [24]. In this case, the radical
expulsion of a carbon-centered radical formed from bromoacetal (35) undergoes
and a cobalt (II) species. The latter is an intramolecular 5-exo-trig cyclization
easily reduced at −0.8 V to reconvert it onto the olefin of the cyclopentene ring,
to a cobalt (I) intermediate that reenters thereby generating a new radical capable of
the catalytic cycle by reacting with a undergoing another reaction. When it was
second molecule of the halide. The radical intercepted intermolecularly by ynone (36),
is capable of undergoing a number enone (37) was produced in a 55% yield
of interesting transformations, including (Scheme 10).
conjugate addition to a Michael acceptor. The chemistry takes place via the
The example illustrated in Scheme 9 reduction of vitamin B12 or a similar
provided a straightforward route to ester cobalt (III) species (38) in a process that
O O
CO2Me
O O
−1.2 V, 0.2 M LiClO 4/DMF
I 10 mol% B12, visible light CO2Me
(60%)
(33)
(32)
OAc
(34), california red scale pheromone
Scheme 9 Vitamin B12 -mediated Michael addition.
EtO OEt
Br
O O
O (36)
−0.9 V, 0.3 M LiClO 4/DMF C5H11

1.8 mol% B12, visible light
(55%) TBDMSO O
TBDMSO
(35) (37)
Scheme 10 Vitamin B12 -mediated cyclization and conjugate addition to prostaglandin PGF2α .
sees the conversion of cobalt from the serves as the supporting electrolyte, DMF
+3 to the +1 oxidation state, and the as solvent, and ammonium bromide as the
opening of two sites of unsaturation proton donor.
(Scheme 11) [25]. This nucleophilic inter-
mediate reacts rapidly with the alkyl halide 11.2.6
to form the octahedral complex (39) and Organonickel and Organopalladium
reestablish a +3 oxidation state on cobalt. Reagents
Reduction of (39) expels either a radical
or a carbanion and regenerates the nucle- β-Bromoacetals and β-bromoacetates read-
ophilic cobalt (I) intermediate. ily undergo nickel (II) catalyzed cyclization
Typically, the reactions are carried out onto alkenes [6, 7]. The process, illustrated
using a controlled potential, with the po- in Scheme 12, has its nonelectrochemi-
tential set to a value that allows the selective cal counterpart in free radical chemistry
reduction of Co(III) in the presence of as well as in the vitamin B12 -mediated
the alkyl halide and Michael acceptor [26]. chemistry discussed previously. It provides
Only 1–20 mol % of the cobalt mediator an exceptionally powerful method for the
is needed. The reactions are conducted in construction of six-membered rings un-
a medium in which lithium perchlorate der ‘‘environmentally friendly’’ conditions,
−0.9 V (SCE) R-Hal Co(III)

Co(III)XY Co(I)
−X, −Y
(38) Hal
−1.5 V (SCE)
• (39)
R/R −Hal−
Scheme 11 Carbanion formation from alkyl halides and cobalt (III) species.
EtO O EtO O
H −1.5 V (Ag/AgCl), 10 mol % H
Br [Ni(cyclam](ClO4)2, NH4ClO4
0.1 M Et4NClO4, DMF, (88%) H
CO2Me CO2Me
(41)
(40)
HN NH
Ni (ClO4)2 = Ni(cyclam)(ClO4)2 N
N
HN NH H H
•
•
(42), R = H, dihydrocorynantheol • OH
(44) (43), R = Et, dihydroantirhine R
Scheme 12 Nickel cyclam mediated intramolecular reductive cyclization.

11.2 Reduction 323
requiring only 10 mol % of the nickel cy- electrogenerated organometallics [27]. El-
clam complex (44) to be effective. Use egant mechanistic studies of several very
of this complex to mediate the process important palladium-catalyzed reactions,
avoids the use of high dilution that is including the Heck reaction, have been
often required of organotin-promoted rad- described within the last five years. The
ical reactions. Cyclization is most effective reader is referred to the original literature
when an electron-deficient alkene is uti- for insight concerning the beautiful way
lized. The product of the reaction of in which the tools common to the field of
bromoenoate (40) is the tetrahydropyranyl electrochemistry can be used to elucidate
ester (41), an intermediate that has been reaction mechanism [8].
used in a synthesis of Ipecac and Corynan- The first example illustrated in
the alkaloids (42) and (43). Scheme 13 portrays a novel route to
In the presence of certain metals, par- the cephalosporin derivative (47) [28, 29]
ticularly nickel and palladium, allylic and through the intermediacy of the allyl nickel
aryl halides serve as convenient sources of species (46). The second example provides
R1 SSO2Ph R1 SSO2Ph R1 S
Br NiBr
N CH2 N
C *, 53% N
O O O
CO2R2 CO2R2 CO2R2
(45) (46) (47)
*NiCl2(bpy) (0.1 equiv), PbBr2 (0.05 equiv), Pt-Al, CC (6.7 mA cm−2, 3.23 F mol−1)
R1 = NHCOCH2Ph
R2 = CH2C6H4OMe-p
R
R R PdBr R
Br PdBr
Pd(0) 2e, −Br
−Pd(0)
N N N
CO2Et N
CO2Et CO2Et CO2Et
(48) (49) (50) (51)
El
R
E
Pd//Pt, PdCl2(PPh3)2 (0.05 equiv),
PPh3 (0.1 equiv), Et4NOTs, DMF,
2.5 mA cm−2 (4 F mol−1), El N
CO2Et
(52), E = CO2H, R = H, 81%

(53), E = H, R = Me, 33%
(54), E = CO2H, R = Ph, 67%
Scheme 13 Organonickel and organopalladium mediated routes of cephalosporin analogs

and indoles.
a convenient means of synthesizing an alkaline alcoholic solution (5–10% neu-

indoles using a transformation that is tralized carboxylic acid) between platinum
reminiscent of a Heck reaction [30]. electrodes in an undivided cell. Further
oxidation of the radical leads to a car-
bocation that is typically intercepted by
11.3 the alcoholic solvent to give rise to the
Oxidation so-called non-Kolbe product. The latter
pathway is favored by low current den-
11.3.1 sity, the use of graphite electrodes, salt
Kolbe Oxidation additives, and an alkaline medium [32].
Conversely, high current density, the use
Perhaps the best-known and most widely of platinum electrodes, an acidic medium,
appreciated electrochemical transforma- and electron-releasing groups favor the
tion is the Kolbe oxidation (see also Kolbe pathway [32].
Chapter 6) [1, 2, 31]. The process involves A good example of the simplicity and
the one electron oxidation of the salt of power of the chemistry to rapidly construct
a carboxylic acid, and the loss of carbon complex systems is provided by the Kolbe
dioxide to afford a radical, R• , that sub- dimerization of (55) as the key step of a total
sequently engages in coupling reactions. synthesis of the triterpene (+)–α-onocerin
Both symmetrical (R• + R• ) and nonsym- (57; Scheme 14) [33]. Thus, oxidation of

metrical (R• + R • ) radical couplings are (+)–hydroxy keto acid (55) in methanol
known and are illustrated in the following containing a trace of sodium methoxide
discussion. The nonsymmetrical variety and at a temperature of 50 ◦ C, followed by
(often referred to as a mixed or hetero acylation and chromatography, provided
coupling) is remarkable given that it re- (+)–diacetoxydione (56) in a 40% yield.
quires the cogeneration and reaction of Nonsymmetrical coupling reactions
more than one reactive intermediate. have been used extensively to generate
A typical Kolbe electrolysis experiment natural products [32, 34–41]. A typical
calls for the constant current electrolysis of procedure calls for the use of a large excess
O
H
CO2H
[a] MeOH, NaOMe
O 0.1 amp, 50 V O
2 OAc
H [b] Ac2O/pyr
H
(40% a & b)
HO AcO
H H H
(55) (56)
OH
H
HO
H
(57), (+) − a-onocerin
Scheme 14 Kolbe oxidation en route to onocerin.

11.3 Oxidation 325
(5–10 equivalents) of one of the acids. unmasked the second carboxylic acid unit,
The insect pheromone looplure (61) was which served nicely in a mixed coupling
synthesized by using the nonsymmetrical reaction with (65) (1 : 10 64/65) to provide
coupling illustrated in Scheme 15 [35]. a rapid and efficient (62%) access to the
Electrolysis of (58) and (59) (1 : 2 ratio) alkene (66); epoxidation afforded the insect
provided only moderate yields of the pheromone disparlure (67).
desired coupling product (60) (26–35%), The radical produced from the oxida-
but the use of a tenfold excess of tive decarboxylation may also be trapped
monomethyl glutarate (59) increased the intramolecularly to form five- and six-
yield to 55%. membered rings (Scheme 17). The Kolbe
Of interest is the fact that one of protocol avoids the use of the toxic organ-
the coupling partners in the looplure otin reagents that are commonly used in
synthesis was the half acid-half ester (59). the formation of radicals. Moreover, when
Since the ester was untouched in the alkyltin hydride reagents are used, a C−H
coelectrolysis, it could potentially function bond is formed. The Kolbe reaction proto-
as a site for a second Kolbe oxidation col, on the other hand, allows the radical
and subsequent coupling. This strategy formed after cyclization to be captured by a
was utilized in the synthesis of disparlure different radical in a coelectrolysis experi-
(67; Scheme 16) [36]. A mixed coupling ment, rather than being reduced. This tan-
between the half-acid ester (62) and dem sequence of events has been exploited
nonanoic acid (63) (1 : 10 ratio) proceeded in the construction of prostaglandin pre-
smoothly to afford (64). Saponification cursor (70) [37–41]. Here, the cyclized
CO2H
CO2Me OAc
(58) ( )6
C4H9 KOH/MeOH
500 mA cm−2 C4H9
C4H9
(55%)
MeO2C CO2H (60) (61), looplure
(59)
Scheme 15 Mixed Kolbe oxidation as a route to an insect pheromone.
[a] Me(CH2)7CO2H (63) Me2CH(CH2)2CO2H (65)

CH3(CH2)9
HO2C Pt anode, MeOH Pt anode, MeOH
[b] KOH, MeOH; H + (62%)
(48%)
MeO2C
HO2C
(62) (64)
CH3(CH2)9
CH3(CH2)9
O
(CH3)2CH(CH2)4
(CH3)2CH(CH2)4
(66) (67), disparlure
Scheme 16 Mixed Kolbe electrolysis route to disparlure.

HO2C
OEt
OEt
−e O
O −CO2 MeO2C
MeO2C
(68) (69)
R OEt
R
(33–35%)
O
MeO2C
(70), R = Me, (CH2)2CO2Me
Scheme 17 Tandem Kolbe electrolyses.
radical (69) is intercepted by an alkyl rad- These substrates possess several oxidiz-
ical, R• , generated by the oxidation of a able sites. Racemic laudanosine (71), for
fourfold excess of co-acid. example, could be oxidized at nitrogen
or in one or both of the electron-rich
11.3.2
aromatic rings. In fact, it displays five volta-
Arene Oxidations
metric peak potentials at 0.63, 0.81, 1.13,
The power and utility of the anode as a se- 1.30, and 1.47 V (vs Ag/AgNO3 ). Yet, using
lective oxidant is highlighted beautifully by potential control, it proved a simple mat-
the electrooxidative cyclization of 1-benzyl- ter to oxidize a dimethoxyaryl unit in the
tetrahydroisoquinolines (Scheme 18) [42]. presence of the N -methylamine subunit.
MeO MeO a
NMe NMe
MeO MeO
−e
MeO MeO
MeO b
MeO
(71) (72)
1.1 V, CH 3CN,
Na2CO3, LiClO4 [a] Cyclization
(Ca to Cb)
(52%)
[b] −e
OMe
OMe
MeO
MeO
b
aq. Na 2CO3
MeO
NMe a
NMe
MeO MeO
O (74) (73)
Scheme 18 Intramolecular oxidative coupling of laudanosine.

11.3 Oxidation 327
The preparative scale oxidation of laudano- product (85) when R = H, and to (86) when
sine (71) at +1.1 V led to the isolation R = OMe. These materials were converted
of a 52% yield of O-methylflavinantine to the natural products (87) and (88) in the
(74) [42, 43]. The mechanism for this ex- manner shown in Scheme 20 [48].
ceptionally useful means of synthesizing In the second instance, the electrochem-
the morphine class of alkaloids is illus- ically generated bromoquinone monoketal
trated in Scheme 18. (90) was converted to the organolithium
Several elegant syntheses of anthra- reagent (91) (Scheme 21) [46, 47]. Its reac-
cyclinone aglycons are based on the tion with ketal (92), a synthon for the 1,4-
ability to intercept the intermediate rad- dipole (93) [49, 50], proceeded smoothly
ical cation (76) formed from the ox- to afford, after sequential treatment with
idation of aromatic ethers (75) and aqueous acid and boron tribromide, a 60%
(79) in situ with alkanols [9, 44, 45]. yield of α-citromycinone (94).
Inter- and intramolecular capture can
occur. As illustrated in Scheme 19, the 11.3.3
methodology leads to the facile construc- [5 + 2] Cycloadditions to Oxidized
tion of substituted quinone mono- and Aromatics
bisketals.
Substituted quinone ketals, prepared in The oxidative electrochemistry of phenols
this manner, serve nicely in annelation has been developed elegantly [51, 52]. The
strategies leading to natural products. Two key intermediate is often the pentadienyl
are illustrated, one in Scheme 20 leading cation (96) that is formed after the loss
to (+)–4-demethoxydaunomycinone (87) of two electrons and one proton from
and (+)–daunomycinone (88) [46–48], the (95) (Scheme 22). It can be intercepted
other in Scheme 21 serving as a pathway by alkenes, at the terminal carbons of
to α-citromycinone (94). The first calls the pentadienyl array, to achieve a [5 + 2]
for a Michael addition of (84) to quinone cycloaddition (e.g. (96) to 97), or by a
ketal (83) followed by capture of the in- nucleophilic solvent such as methanol,
termediate enolate, and leads to annelated leading to a conjugated diene (99). The
OMe OMe MeO OMe MeO OMe

−e CH3OH CH3OH
−e, −H+ −H+
MeO OMe
OMe OMe OMe
(75) (76) (77) (78)
OMe O
MeO OMe
R R R
−2e H+
KOH, MeOH (78–94%)
(66–81%)
O O O O
OCH2CH2OH
(79) (80) (81)
Scheme 19 An expeditious synthesis of quinone ketals.

OMe O
O MeO OMe O O
[a] −2e, KOH MeOH
OH
[b] AcOH OH
OMe OTBDMS (64%, a + b) O OTBDMS

(82) (83) NC
Li
[a] O
R O
(84)
[b] F
O OH O O OMe O
O
OH [a] HCl, THF OH

[b] BCl3
R O OH OH R O OMe OTBDMS
(87), 4-demethoxydaunomycinone, R = H (98%) (85), R = H (90%)

(88), daunomycinone, R = OMe (86%) (86), R = OMe (64%)
Scheme 20 An elegant route to anthracycline anitibiotics.
MeO OMe OCH2OCMe MeO OMe OCH2OCMe

Br Li
Steps
OCH2OCMe OCH2OCMe
O OCH2OMe TBDMSO OCH2OMe

(90) (91)
[a] TMEDA
[a] −2e KOH, MeOH O O
(87%) O
[b] H3O+ (71%) OMe

O
(92)
OR O [b] H3O+
OMe OCH2OCMe [c] BBr3 (60%)
(93)
Br
O OH OH
OCH2OCMe
OMe OCH2OMe OH
(89) OH O OH
(94), a-citromycinone
Scheme 21 Electrooxidation and annelation en route to α-citromycinone.

11.3 Oxidation 329
Y Y Y Y
R
Z Z OMe O
−2e, −H+ R′
X X X X
OH O R R′ R R′
O O
(95) (96)
(97) (98)
MeOH
Y R2 R3
Z R2
R3 MeO Y
MeO
X O X
O Z
(99) (100)
Scheme 22 Opportunities for [5 + 2] and [4 + 2] cycloaddition.
latter constitutes a useful and a novel route is not nearly as efficient. Two products,
to Diels–Alder dienes. (105b) and (106) (futenone) are produced
Both inter- and intramolecular [5 + 2] in a yield of 25 and 15%, respectively.
cycloaddition modes have been utilized in Notice the different current densities that
the synthesis of natural products. Success- are associated with these transforma-
ful intermolecular cycloaddition depends tions, 10 mA cm−2 for the reaction con-
on making an appropriate selection of ducted in MeOH/AcOH, 0.27 mA cm−2 in
solvent, supporting electrolyte, oxidation AcOH/TFA (trifluoroacetic acid). It turns
potential, and current density. This is out that the success of many of the cycload-
nicely illustrated in Schemes 23 to 25. For ditions depends on finding the optimal
example, in methanol the controlled poten- current density.
tial oxidation of phenol (101) affords a high Asatone (110; Scheme 25), a neolignan,
yield (87%) of (102), the adduct wherein was quickly assembled by capitalizing
methanol has intercepted the reactive in- upon the ability of a nucleophilic solvent to
termediate [51]. In contrast, a constant intercept the intermediate cation formed
current electrolysis conducted in acetoni- upon the electrooxidation of (108); in this
trile rather than methanol, led to an 83% instance the conjugated 1,3-diene (109)
yield of quinone (103). was produced. This result contrasts with
As the examples portrayed in Scheme 24 the oxidation of 4,5-dimethoxyphenol (101)
show [51], cycloaddition is often carried (Scheme 23) wherein the nonconjugated
out in mixed solvent systems consisting of 1,4-diene (102) was generated. Diene (109)
either methanol/acetic acid (2 : 1) or acetic served admirably as both the diene and
acid/trifluoroacetic acid (4 : 1) with lithium the dienophile in an intermolecular Diels–
perchlorate as supporting electrolyte. Cy- Alder reaction leading to asatone (110) [51].
cloaddition between the oxidized form The intramolecular [5 + 2] cycloaddi-
of (101) and alkene (104E) leads to the tion mode has been studied exten-
neolignan (105a) in high yield, and with sively. The chemistry bears a remark-
preservation of the olefin geometry. When able similarity to the arene-olefin meta-
the Z-isomer (104Z) is used, the chemistry photocycloaddition [53] reaction (e.g. 114
OMe MeO OMe

OMe Controlled potential
OMe
MeOH, LiClO4 (87%)
OH O
(101) O (102)
CCE, aq MeCN
n-Bu4NBF4 (83%)
OMe
O
(103)
Scheme 23 The influence of reaction conditions upon the oxidation of phenols.
OMe O (104E) R
O
OMe CCE at 10 mA
+ MeOH/AcOH (2/1) O OMe
R1
R LiClO4 (81%)
R2 O
OH
(104E) (E-isomer)
(105a)
(101), R = allyl (104Z) (Z-isomer)
R = allyl, R1 = H, R2 = Ar
CCE at 0.27 mA
(104Z) AcOH/CF3CO2H (4/1)
LiClO4 (25% (105b), 15% (106)) O = Ar
O
R
O
O
O OMe H
OMe O O
R1
R2 O Ar
OMe
(105b)
R = allyl, R1 = Ar, R 2 = H (106), futenone Ar (107)
Scheme 24 The [5 + 2] cycloaddition approach to natural product skeleta.
R′ R′
R′ O R
CCE at 5 mA R
MeOH, LiClO4 R
MeO Diels-Alder R
MeO OMe (34%) Dimerization
OMe R
OH MeO R
O R′ O
(108), R′ = allyl (109)
(110), R = OMe, R′ = allyl
asatone
Scheme 25 The [4 + 2] cycloaddition approach to natural product skeleta.

11.3 Oxidation 331
to 115) that has frequently been used in 11.3.4

the synthesis of complex bioactive natu- Oxidation at and Adjacent to Nitrogen
ral products. While different intermediates
are involved, the photo- and electrochem- Amines and amides undergo oxidation
ical reactions provide access to many at or adjacent to nitrogen (Scheme 27).
of the same ring systems. The similar- A neutral amine, for example, can be
ity is nicely illustrated in Scheme 26 by oxidized to afford a cation radical (117
comparing key steps of an electrochem- to 116). Similarly, electrooxidation of the
ical approach to the total synthesis of anion produced via deprotonation of a
the angularly fused sesquiterpene pental- secondary amine leads to an aminyl
enene [54], and a photochemical pathway radical (119) that is capable of partici-
that ultimately led to the sesquiterpene pating in carbon–nitrogen bond-forming
cedrene. reactions with remotely tethered alkenes.
OMe OMe
OMe MeO O
MeO
CCE, MeOH/AcOH
LiClO4 (64%)
R O
OH O
OAc
R = CH(CH3)CH2CH2CH CHCH2OAc AcO (113)
(111) (112)
1. hn (70%)
2. Br 2, CCl4
3. R 3SnH
OMe O
(114) (115)
Scheme 26 Comparison of electrochemical and photochemical strategies.
R R′ −e R R′ R R′ R R′
−e
N
N
H Base N −M+ N
H M
(116) (117) (118), M = metal (119)
O O
NR −e, −H+ NR
a
(120) (121)
Scheme 27 Oxidation at and adjacent to nitrogen.

Amides (carbamates) (120) are susceptible A 5-exo-trig cyclization of the metalated

to oxidation at alkyl centers adjacent to aminyl radical provided pyrrolidine (123)
nitrogen. as a single isomer in a 53% yield. A rou-
Indicative of the chemistry of the tine series of transformations converted it
aminyl radical (119) is a synthesis of to the target structure (124).
the N -methyl derivative of the antibi- The vinblastine alkaloids are important
otic (–)-anisomycin (124; Scheme 28) [55]. chemotherapeutic materials, and are well
Pyrrolidine (123) was obtained by treat- known for their antitumor properties. A
ing (E)-δ-alkenylamine (122) with n- two-electron oxidation of alkaloid cantha-
butyllithium at −78 ◦ C, followed by oxida- ranthine (125) followed by nucleophilic
tion at a constant current (17.5 mA cm−2 ) capture of the resulting imminium ion
in a 100 : 1 mixture of THF and HMPA (126) by C10 of vindoline (127), afforded
containing 0.25 M lithium perchlorate (128) and provided access to this impor-
as the supporting electrolyte at −10 ◦ C. tant class of materials (Scheme 29) [56].
MOMO OMe
OMOM OMOM HO OAc
Me 1. n-BuLi
N
2. −e N
OMOM Me Ar N
H OMe Me
(53%)
(122) (123)
(124), (+)-N -methylanisomycin
Scheme 28 Aminyl radical cyclization.
N N
−2e
N N
H H
CO2Me CO2Me
(126)
(125), cantharanthine
[a] MeCN, Et4NClO4,

C10 OAc
0.6 V, vindoline (127) OH
[b] NaBH4 MeO N CO2Me
H
(52%)
(127), vindoline
N N
NaBH4
16 N
N H
H V V
MeO2C MeO2C
(128)
(129), anhydrovinblastine V = 10-vindolinyl
Scheme 29 An elegant electrochemical route to the vinblastine alkaloids.

11.3 Oxidation 333
Oxidation was carried out at a potential Both pyrrolizidine and indolizidine al-
that allowed the selective oxidation of can- kaloids can be synthesized by taking
tharanthine (125). The overall process was advantage of the anodic α-alkoxylation
shown to occur in a stepwise manner with of N -alkoxycarbonylpyrrolidines (e.g. (131)
vindoline (127) intercepting the putative to (132), Scheme 31). The method has
dication (126). Reduction of (128) with been utilized to synthesize isoretronecanol
sodium borohydride afforded anhydrovin- (137), trachelanthamidine (138), elaeoka-
blastine (129) in a 52% yield accompanied nine A (135), and elaeokanine C (136) [57].
by 12% of the material epimeric at C16 . Once the methoxy group has been installed
As indicated previously, amides (carba- and nucleophilic capture of the intermedi-
mates) (120) are susceptible to oxidation ate has occurred, the product (132) can be
at an alkyl center adjacent to nitrogen. treated with an enol ether (e.g. 133) and
The resulting acyl imminium ion (121) titanium tetrachloride to affect C–C bond
can be intercepted by a variety of nucle- formation adjacent to nitrogen. This se-
ophiles in a process that sets the stage quence served nicely in syntheses of both
for subsequent carbon–carbon formation indolizidine alkaloids elaeokanine A (135)
(Scheme 30). As the following discussion and C (136).
illustrates, the creative utilization of this A formal total synthesis of vincamine
protocol provides an exceptionally useful (144) was achieved, once again by capital-
entry to a host of alkaloids. izing upon the ability to affect oxidation
O O O
NR −e, −H+ NR Nu NR
a Nu
(120) (121) (130)
Scheme 30 Nucleophilic addition to an electrochemically generated acyl imminium ion.
O
−2e, MeOH TiCl4 (81%)
N OMe OTMS
N N
CO2Me CO2Me CO2Me
(134)
(131)
(132) (133)
H
R
N
R′ O H O
N N
(137), R = CH2OH, R′ = H
isoretronecanol OH
(138), R = H, R′ = CH2OH
(135), elaeokanine A (136), elaeokanine C
trachelanthamidine
Scheme 31 Indolizidine and pyrrolizidine alkaloid synthesis.

CO2Me
CO2Me
CO2Me
N
CO2H CCE, MeOH HCO2H N O O
MeO N OMe
Et4NClO4
(76%)
Et CO2H Et
Et
(139) (140) (141)
Br
N
N
N N
OH H (142)
Et CO2Me
CO2Me
Et
(144), (+)-vincamine (143)
Scheme 32 An ingenious synthesis of vincamine.
α to nitrogen [58, 59]. Thus, when the treated with formic acid, (140) transformed
piperidine carboxylic acid ester (139) was to lactone (141) in a 76% yield after
oxidized at a constant, it was efficiently chromatography. Hydrogenation, hydroly-
converted to methyl ether (140). When sis, and esterification afforded ester (143).
O O
N −e, −H+ N
G G
(145) (146)
Scheme 33 Anodic cyclization of lactams.
E E E E
E CCE (single cell)
OMe
E TiCl4, CH2Cl2
N Et4NClO4, MeOH N
N (77%)
(71%)
O O O
(149)
(147), E = CO2Me (148)
CO2H CO2H
N N
(151), epilupinine (150), lupinine
Scheme 34 Intramolecular cyclization onto an acyl imminium ion.

11.3 Oxidation 335
The latter served as a key-coupling partner amide and ester units of the resulting
with tryptophyl bromide (142) en route to epimeric esters provided the natural prod-
the assembly of vincamine (144). ucts (150) and (151).
Another useful route to alkaloids in- A convenient method to affect the ox-
volves the electrochemical oxidation of idation β- to nitrogen in piperidines is
lactams (145) bearing functionality on based on the anodic oxidation of N -
nitrogen that can be used to intramolec- carboalkoxy piperidines (Scheme 35). The
ularly capture an intermediate acyl im- electrochemical oxidation of piperidine
minium ion (146). The concept is por- (152) in the presence of acetic acid
trayed in Scheme 33 and is highlighted and potassium acetate, for example, af-
by the synthesis of alkaloids lupinine forded a mixture of isomeric 2-hydroxy-
(150) and epilupinine (151) shown in 3-acetoxypiperidines (153) in a combined
Scheme 34 [60]. Thus, the electrooxidation yield of 93%, following an aqueous
of lactam (147) provided a 71% yield of workup [61]. Reduction with sodium boro-
ether (148). Subsequent treatment with ti- hydride severed the C–OH bond. Treat-
tanium tetrachloride affected cyclization ment with acid and then base completed a
and afforded the [4.4.0] bicyclic adduct synthesis of pseudoconhydrine (154).
(149). Krapcho decarbomethoxylation fol- The anodic α-alkoxylation of amides
lowed by hydride reduction of both the [10–12, 62–65] has been used extensively
OAc
[a] NaBH4 (78%)
OH
AcONa, AcOH
n-Pr N Single cell n-Pr N OH [b] HBr (58%)
(93%) N
H
CO2Me CO2Me
(154)
(152) (153)
pseudoconhydrine
Scheme 35 Synthesis of pseudoconhydrine.
CO2Me
[a] C-anode, Pt-cathode
CO2Me 0.03 M Et4NOTs, MeOH t-BocN
3 F mol−1 (99%)
t-BocN
[b] allylTMS, BF3 (77%)
(156) O
H2N CO2Me
(155) N
Ph
O H
O BzlO CO2Me
BzlO CO2Me
N (159)
N Ph
Ph
(158) (157)
Scheme 36 An elegant synthesis of a peptide mimetic.

in the construction of peptide mimetics. 4. S. Torii, Electroorganic Synthesis, Methods and

Much of the work has focused upon the Applications, Part I: Oxidations, Kodansha,
Tokyo, 1985.
synthesis of conformationally restricted 5. K. Yoshida, Electrooxidation in Organic Chem-
systems in an effort to ascertain the istry, The Role of Cation Radicals as Synthetic
relationship between the bioactivity of Intermediates, Wiley, New York, 1984.
the parent peptide and a specific con- 6. M. Ihara, A. Katsumata, F. Setsu et al., J. Org.
Chem. 1996, 61, 677–684.
former of it. The example illustrated
7. J.-Y. Nedelec, J. Perichon, M. Troupel, Top.
in Scheme 36 portrays an exceptionally Curr. Chem. 1997, 185, 141–173.
clever synthesis of (158), a key substance 8. C. Amatore, A. Jutand, Acc. Chem. Res. 2000,
en route to the Phe-Pro-building block 33, 314–321.
(159) [10–12]. Both the electrooxidation 9. J. S. Swenton, Acc. Chem. Res. 1983, 16,
74–81.
and ring-forming metathesis (157 to 158) 10. K. D. Moeller, D. Grey, L. Matson-Beal et al.,
reactions are of special note. Anodic electrochemistry: recent advances
in the total synthesis of complex organic
molecules in Novel Trends in Electroorganic
Synthesis (Ed.: S. Torii), Springer, New York,
11.4 1998, p. 51.
Concluding Remarks 11. L. M. Beal, K. D. Moeller, Tetrahedron Lett.
1998, 39, 4639–4642.
It is hoped that the examples cited have 12. K. D. Moeller, Top. Curr. Chem. 1997, 185,
provided the reader with a sense of the 49–86.
13. J. P. Petrovich, J. D. Anderson, M. M. Baizer,
wide range of exceptionally useful trans- J. Org. Chem. 1966, 31, 3897–3903.
formations that can be carried out elec- 14. J. P. Petrovich, M. M. Baizer, M. R. Ort, J.
trochemically. It is hoped that some day Electrochem. Soc. 1969, 116, 743–749.
this protocol will be routinely considered, 15. L. Moëns, M. M. Baizer, R. D. Little, J. Org.
Chem. 1986, 51, 4497, 4498.
evaluated for its unique merits, and widely 16. A. J. Fry, R. D. Little, J. A. Leonetti, J. Org.
adopted as a tool that is to be used to solve Chem. 1994, 59, 5017–5026.
problems in organic synthesis. 17. C. G. Sowell, R. L. Wolin, R. D. Little, Tetra-
hedron Lett. 1990, 31, 485–488.
18. A. S. Kende, B. Roth, P. J. Sanfilippo et al., J.
Acknowledgment Am. Chem. Soc. 1982, 104, 5804–5810.
19. T. Shono, N. Kise, Tetrahedron Lett. 1990, 31,
We are grateful to the National Science 1303–1306.
20. T. Shono, N. Kise, T. Fujimoto et al., J. Org.
Foundation for supporting our research
Chem. 1992, 57, 7175–7187.
efforts in the field of organic electrochem- 21. P. A. Wender, K. D. Rice, M. Schnute, J. Am.
istry. Chem. Soc. 1997, 119, 7897, 7898.
22. R. Gorny, H. J. Schäfer, R. Fröhlich, Angew.
Chem., Int. Ed. Engl. 1995, 34, 2007, 2008;
References J. Heimann, H. J. Schäfer, R. Fröhlich,
B. Wibbeling, Eut. J. Org. Chem. 2003,
1. A. J. Fry, Synthetic Organic Electrochemistry, 2919–2932.
2nd ed., Wiley, New York, 1989. 23. R. Scheffold, B12 -catalyzed electrosynthesis
2. M. M. Baizer, H. Lund, Eds., Organic Electro- of natural products in Electroorganic Synthesis
chemistry, An Introduction and a Guide, 4th (Eds.: R. D. Little, N. L. Weinberg), Marcel
ed., Marcel Dekker, New York, 2001. Dekker, New York, 1991, pp. 317–322.
3. K. D. Moeller, Tetrahedron (Tetrahedron Re- 24. R. Scheffold, Chimia 1985, 39, 203–210.
port: Synthetic Applications of Anodic Elec- 25. R. Scheffold, M. Dike, S. Dike et al., J. Am.
trochemistry), 2000, 56, 9527–9554. Chem. Soc. 1980, 102, 3642–3644.
11.4 Concluding Remarks 337
26. R. Scheffold, G. Rytz, L. Walder et al., Pure mechanism in Electroorganic Synthesis (Eds.:
Appl. Chem. 1983, 55, 1791–1797. R. D. Little, N. L. Weinberg), Marcel Dekker,
27. H. Tanaka, S. Sumida, K. Sorajo et al., Ni/Pb New York, 1991, pp. 145–151.
Bimetal-redox mediated reductive addi- 46. D. K. Anderson, C. E. Coburn, A. P. Haag
tion/cyclization of allenecarboxylate with et al., Tetrahedron Lett. 1983, 24, 1329–1332.
allyl bromide in a electrolysis media in 47. J. S. Swenton, D. K. Anderson, C. E. Coburn
Novel Trends in Electroorganic Synthesis (Ed.: et al., Tetrahedron 1984, 40, 4633–4642.
S. Torii), Kodansha, Tokyo, 1995, pp. 193, 48. J. S. Swenton, J. N. Freskos, G. W. Morrow
194. et al., Tetrahedron 1984, 40, 4625–4632.
28. H. Tanaka, Y. Kameyama, S. Sumida et al., 49. D. K. Jackson, L. Narasimhan, J. S. Swenton,
Tetrahedron Lett. 1992, 33, 7029, 7030. J. Am. Chem. Soc. 1979, 101, 3989, 3990.
29. H. Tanaka, Y. Kameyama, S. Sumida et al., 50. J. S. Swenton, D. K. Anderson, D. K. Jackson
Synlett 1991, 888–890. et al., J. Org. Chem. 1981, 46, 4825–4836.
30. H. Tanaka, O. Ren, S. Torii, Pd(0)/Pd(II)- 51. S. Yamamura, Y. Shizuri, H. Shigemori
mediated electroreductive cyclization of n- et al., Tetrahedron 1991, 47, 635–644.
alkenyl-2-bromoanilines in Novel Trends 52. S. Yamamura, Natural products syntheses
in Electroorganic Synthesis (Ed.: S. Torii), by means of electrochemical methodology
Kodansha, Tokyo, 1995, pp. 195, 196. in Electroorganic Synthesis (Eds.: R. D. Little,
31. H. Kolbe, Liebigs Ann. Chem. 1849, 69, 257; N. L. Weinberg), Marcel Dekker, New York,
H. J. Schäfer, Top. Curr. Chem. 1990, 152, 1991, pp. 309–315.
91–151. 53. P. A. Wender, L. Siggel, J. M. Nuss, [3 + 2]
32. E. Klocke, A. Matzeit, M. Gockeln et al., and [5 + 2] arene-alkene photocycloadditions
Chem. Ber. 1993, 126, 1623–1630. in Comprehensive Organic Synthesis (Ed.:
33. G. Stork, A. Meisels, J. E. Davies, J. Am. B. M. Trost), Pergamon Press, New York,
Chem. Soc. 1963, 85, 3419–3425. 1991, pp. 645–673, Vol. 5.
34. J. Knolle, H. J. Schäfer, Angew. Chem., Int. 54. Y. Shizuri, S. Maki, M. Ohkubo et al., Tetra-
Ed. Engl. 1975, 14, 758. hedron Lett. 1990, 31, 7167, 7168.
35. W. Seidel, J. Knolle, H. J. Schäfer, Chem. Ber. 55. M. Tokuda, H. Fujita, T. Miyamoto et al.,
1977, 110, 3544–3552. Tetrahedron 1983, 49, 2413–2426.
36. H. Klünenberg, H. J. Schäfer, Angew. Chem., 56. E. Gunic, I. Tabakovic, M. J. Gasic, J. Chem.
Int. Ed. Engl. 1978, 17, 47, 48. Soc., Chem. Commun. 1993, 1496, 1497.
37. L. Becking, H. Schäfer, Tetrahedron Lett. 57. T. Shono, T. Matsumura, K. Uchida et al., J.
1988, 29, 2801, 2802. Org. Chem. 1984, 49, 300–304.
38. A. Matzeit, H. J. Schäfer, C. Amatore, Syn- 58. S. D. Ross, M. Finkelstein, R. C. Petersen, J.
thesis 1995, 1432–1444. Am. Chem. Soc. 1966, 88, 4657–4660.
39. M. Harenbrock, A. Matzeit, H. J. Schäfer, 59. K. Irie, Y. Ban, Heterocycles 1982, 18,
Liebigs Ann. Chem. 1996, 55–62. 255–258.
40. U. Jensen, H. J. Schäfer, Chem. Ber. 1981, 60. M. Okita, T. Wakamatsu, Y. Ban, Heterocycles
114, 292–297. 1983, 20, 401–404.
41. W. Seidel, H. J. Schäfer, Chem. Ber. 1980, 61. T. Shono, Y. Matsumura, S. Onomura et al.,
113, 451–456. Chem. Lett. 1984, 1101–1104.
42. L. L. Miller, F. R. Stermitz, J. R. Falck, J. Am. 62. K. D. Moeller, L. D. Rutledge, J. Org. Chem.
Chem. Soc. 1971, 93, 5941, 5942. 1992, 57, 6360–6363.
43. L. L. Miller, F. R. Stermitz, J. R. Falck, J. Am. 63. W. Li, C. E. Hanau, A. d’Avignon et al., J.
Chem. Soc. 1973, 95, 2651–2656. Org. Chem. 1995, 60, 8155–8170.
44. M. G. Dolson, J. S. Swenton, J. Am. Chem. 64. L. V. Tinao-Wooldridge, K. D. Moeller, C. M.
Soc. 1981, 103, 2361–2371. Hudson, J. Org. Chem. 1994, 59, 2381–2389.
45. J. S. Swenton, Anodic methoxylation of aro- 65. K. D. Moeller, S. L. Rothfus, Tetrahedron Lett.
matic compounds occurring via the EECrCp 1992, 33, 2913–2916.
339
12
Electrochemistry of Heterocycles
Claude Moinet
University of Rennes, Rennes, France
12.1 Overview on the Electrochemistry of Heterocycles . . . . . . . . . . . . . 341

12.1.1 Electrosyntheses of Heterocycles . . . . . . . . . . . . . . . . . . . . . . . . 341
12.1.1.1 Anodic Cyclizations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341
12.1.1.2 Cathodic Cyclizations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343
12.1.2 Electrochemical Behavior of Heterocycles . . . . . . . . . . . . . . . . . . 345
12.1.2.1 Oxidation of Heterocycles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
12.1.2.2 Reduction of Heterocycles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346
12.2 Oxidative Cyclizations at the Anode . . . . . . . . . . . . . . . . . . . . . . 346

12.2.1 Intramolecular Cyclizations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346
12.2.1.1 Carbon–Carbon Bond Formation . . . . . . . . . . . . . . . . . . . . . . . . 346
12.2.1.2 Carbon–Heteroatom Bond Formation . . . . . . . . . . . . . . . . . . . . . 348
12.2.1.2.1 Carbon–Oxygen Bond For-mation . . . . . . . . . . . . . . . . . . . . . . . 348
12.2.1.2.2 Carbon–Nitrogen Bond For-mation . . . . . . . . . . . . . . . . . . . . . . 350
12.2.1.2.3 Carbon–Sulfur Bond Formation . . . . . . . . . . . . . . . . . . . . . . . . 354
12.2.1.3 Heteroatom–Heteroatom Bond Formation . . . . . . . . . . . . . . . . . 354
12.2.1.3.1 Nitrogen–Nitrogen Bond Formation . . . . . . . . . . . . . . . . . . . . . . 354
12.2.1.3.2 Nitrogen–Oxygen Bond Formation . . . . . . . . . . . . . . . . . . . . . . . 355
12.2.2 Intermolecular Coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
12.2.2.1 Heterocoupling Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
12.2.2.1.1 Cycloaddition Reactions with Alkenes . . . . . . . . . . . . . . . . . . . . . 355
12.2.2.1.2 Cycloaddition Reactions with Other Nucleophiles . . . . . . . . . . . . . 359
12.2.2.2 Homocoupling Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359
12.3 Reductive Cyclization at the Cathode . . . . . . . . . . . . . . . . . . . . . . 361

12.3.1 Intramolecular Cyclization . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
12.3.1.1 Carbon–Carbon Bond Formation . . . . . . . . . . . . . . . . . . . . . . . . 361
12.3.1.2 Carbon–Heteroatom Bond Formation . . . . . . . . . . . . . . . . . . . . . 364
12.3.1.2.1 Carbon–Oxygen Bond Formation . . . . . . . . . . . . . . . . . . . . . . . . 364
340 12 Electrochemistry of Heterocycles
12.3.1.2.2 Carbon–Nitrogen Bond Forma-tion . . . . . . . . . . . . . . . . . . . . . . 364

12.3.1.3 Heteroatom–Heteroatom Bond Formation . . . . . . . . . . . . . . . . . 367
12.3.1.3.1 Nitrogen–Nitrogen Bond Formation . . . . . . . . . . . . . . . . . . . . . . 367
12.3.2 Intermolecular Cyclization . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
12.3.2.1 Heterocoupling Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
12.3.2.2 Homocoupling Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369
12.4 Anodic Oxidation of Heterocycles . . . . . . . . . . . . . . . . . . . . . . . . 369

12.4.1 Double Bond Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369
12.4.2 Functionalization of Heterocycles . . . . . . . . . . . . . . . . . . . . . . . . 372
12.4.2.1 Methoxylation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
12.4.2.2 Acetoxylation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
12.4.2.3 Hydroxylation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375
12.4.2.4 Cyanation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375
12.4.2.5 Halogenation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
12.4.2.6 Trifluoromethylation Reactions . . . . . . . . . . . . . . . . . . . . . . . . . 379
12.4.2.7 Intramolecular Coupling Reactions . . . . . . . . . . . . . . . . . . . . . . . 379
12.4.2.8 Dimerization Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379
12.4.3 Ring Expansions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
12.4.4 Ring Contractions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382
12.4.5 Ring Opening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382
12.5 Cathodic Reduction of Heterocycles . . . . . . . . . . . . . . . . . . . . . . 382

12.5.1 Electroreductive Hydrogenation of Double Bonds . . . . . . . . . . . . . 382
12.5.2 Functionalization of Heterocycles . . . . . . . . . . . . . . . . . . . . . . . . 386
12.5.2.1 Addition Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386
12.5.2.2 Substitution Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
12.5.2.3 Intramolecular Coupling Reactions . . . . . . . . . . . . . . . . . . . . . . . 388
12.5.2.4 Dimerization Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 388
12.5.3 Ring Expansions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 390
12.5.4 Ring Contractions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 390
12.5.5 Ring Opening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
341
12.1 two separated steps. Coupling reactions

Overview on the Electrochemistry of can occur by either direct electrolysis or
Heterocycles by using transition metal complexes as
catalysts. Bond formations result from car-
Heterocycles are of great interest in or- bon–carbon, carbon–heteroatom, or het-
ganic chemistry due to their specific prop- eroatom–heteroatom coupling reactions.
erties. Many of these cycles are widely It is worth noting that anodic oxidations
present in natural and pharmaceutical often give electrophilic and/or acidic cen-
compounds. Electrochemistry appears as ters, whereas cathodic reductions lead to
a powerful tool for the preparation and the nucleophilic and/or basic centers. More-
functionalization of various heterocycles over, we must keep in mind that the
because anodic oxidations and cathodic re- mechanisms of many anodic and cathodic
ductions allow the selective preparation cyclizations are not accurately known.
of highly reactive intermediates (radicals,
radical ions, cations, anions, and elec- 12.1.1.1 Anodic Cyclizations
trophilic and nucleophilic groups). In this Various reactive intermediates have been
way, the electrochemical technique can be postulated in the formation of heterocycles
used as a key step for the synthesis of com- by anodic oxidation.
plex molecules containing heterocycles. A Radical cations resulting from oxidation
review of the electrolysis of heterocyclic of olefins, aromatic compounds, amino
compounds is summarized in Ref. [1]. groups, and so on, can react by elec-
trophilic addition to a nucleophilic center
12.1.1 as shown, for example, in Scheme 1 [2, 3].
Electrosyntheses of Heterocycles The double bond activated by an electron-
donating substituent is first oxidized lead-
Ring-closure reactions occur either by ing to a radical cation that attacks the
intramolecular coupling when the elec- nucleophilic center. The global reaction is
trogenerated center and the other reac- a two-electron process corresponding to an
tive center are in appropriate positions ECEC mechanism.
within the molecule, or by intermolec- Radicals prepared by anodic oxidation
ular coupling. In this latter case, the of anions or by the Kolbe reactions can
ring formation involves the creation of couple with other radicals or add to double
two bonds either simultaneously or in bonds. For instance in Scheme 2 [4, 5], the
MeO MeO MeO MeO

• • OMe
H
OH −e O+ −H+ O −e, CH3OH O
R R R R
( )n ( )n ( )n −H+ ( )n
(80–96%)
n = 1; R = Me, CH2Ph
n = 2; R = H
Scheme 1 Intramolecular reaction of a radical cation with a nucleophile.
R
CO2H
•
−e − CO2
+ RCO2H + R•
X −H+ X X
X = O, NCOCH 3, NCOH (45–67%)

R = CH3, n-C5H11, (CH2)4CO2CH3
Scheme 2 Intramolecular addition of a Kolbe radical to a double bond.
initial radical generated by a Kolbe reaction deprotonation reactions are favored by the
adds to a double bond within the molecule presence of bases in the medium.
prior to trapping the radical from a second More generally, electrolytically formed
carboxylic acid. electrophilic centers react with nu-
Cations resulting from a two-electron cleophilic centers. For example, in
oxidation of carboxylic acids (non-Kolbe Scheme 4 [7], an electrogenerated nitroso
electrolysis) or from compounds having group leads to a nitrogen–nitrogen bond
protons in the α-position to heteroatoms formation after reaction with an amino
as shown in Scheme 3 [6] react with group. When the electrolysis is performed
nucleophilic centers. In the last case, in a batch cell, a rapid cyclization
•+
−e
H3C N CH2CH2OH H3C N CH2CH2OH
CO2CH3 CO2CH3
−H+
• −
H2C N CH2CH2OH O
−e − H+
CO2CH3 N
H3CO2C
(60%)
Scheme 3 Intramolecular reaction of an electrogenerated carbocation with a nucleophile.

12.1 Overview on the Electrochemistry of Heterocycles 343
CH2 NHR CH2 NHR

−2e − 2 H+ −H2O
N R
NHOH NO N
R = CH3, Ph
Scheme 4 Intramolecular reaction of an electrogenerated electrophile with a nucleophile.
is necessary to avoid a coupling reac- Radicals can be obtained from reduction

tion between the starting hydroxylamino of molecules followed either by protonation
compound (previously produced by the or departure of a nucleophile as illustrated
cathodic reduction of the correspond- in Schemes 6 [10] and 7 [11], respectively.
ing nitro compound) and its nitroso In the first example, a generally accepted
derivative. mechanism involves a reduction of a
Anodically electrogenerated species can double bond activated by an electron-
undergo cycloaddition reactions with other withdrawing group to a radical anion
reagents. For example, in Scheme 5 a followed by protonation and cyclization
diazenium cation reacts with styrene [8, 9]. of the resulting radical. The addition of a
second electron and proton completes the
12.1.1.2 Cathodic Cyclizations process.
Cathodic cyclizations also involve various In the second example, the aryl
reactive intermediates. radical obtained after cleavage of the
C6H5
C6H5 C6H5
C6H5 N
−2e − H+ + NH
N NH2 N NH
C6H5 C6H5
C6H5
(95%)
Scheme 5 Cycloaddition of an electrogenerated electrophile.
H H
N N
CH CHCO2Et +e + H+ CH
•
CH2CO2Et
CH CHCO2Et CH CHCO2Et
N N
H H
H H
N CH2CO2Et +e + H+ N CH2CO2Et
•
N CHCO2Et N CH2CO2Et
H H
(86%)
Scheme 6 Intramolecular reaction of a radical anion with an electrophile.

Br N N N N
N • N
N +e − Br−
N
F F
N N N N
N N
−H
•
N N
H •
F F
(91%)
Scheme 7 Intramolecular addition of an electrogenerated radical to an aryl ring.
carbon–halogen bond leads to a fast More generally, electrolytically pro-

intramolecular cyclization. duced nucleophilic centers (amine, hy-
Radical anions resulting from ca- droxylamine, hydrazine, alcohol) react
thodic reductions of molecules react with electrophilic centers (carbonyl group,
with electrophilic centers. As an example cyano group, nitroso group) as illustrated
(Scheme 8), the reduction of compounds in Scheme 9 for the synthesis of N -
in which a double bond is not conjugated hydroxyindoles [13].
with a carbonyl group, involves an in- Cathodically electrogenerated species
tramolecular coupling reaction of radical can give cycloaddition reactions with
anion with alkene [12]. other reagents. This can be illustrated
H3C OH
O O−
• + H3C
+e +e + 2H
N N N
R R R
R = CH2CH = CH2, n.C3H7, n.C4H9 (26–36%)
Scheme 8 Intramolecular addition of a radical anion to an alkene.
R1
CHR1COR2 CHR1COR2
+4e + 4H+ −H2O R2
R3 NO2 −H2O R3 NHOH R3 N
R1 = R3 = H; R 2 = CH3, Ph, CO2H, CO2Et OH

R2 = CH3; R 3 = CF3; R 1 = CO2Et, COCH3, Ph
Scheme 9 Intramolecular reaction of a cathodically generated nucleophile with an electrophile.

12.1 Overview on the Electrochemistry of Heterocycles 345
C6H5 C6H5
+2e N N
C6H5 N N C6H5 + 2Br−
+Br(CH2)4Br
(81%)
Scheme 10 Cathodic bisalkylation of azobenzene with 1,4-dibromobutane.
by the cathodic reduction of azobenzene Oxidations of heterocycles can afford for-

in the presence of 1,4-dibromobutane mations of double bonds. This is illustrated
(Scheme 10) [14, 15]. by the anodic oxidation of dihydropy-
ridines (Scheme 11) [16] for which pyri-
12.1.2 dinium cations are produced according to
Electrochemical Behavior of Heterocycles an ECE mechanism. Unsubstituted dihy-
dropyridines at carbon 4 give pyridines.
Electrochemistry is also a powerful means Anodic oxidations can produce cationic
of modifying heterocycles. According to species that react with nucleophiles. For
the electrochemical process (oxidation or example, the oxidation of N -phenylpiperi-
reduction) several types of reactions can dine performed in the presence of cyanide
take place: unsaturation or saturation of ions affords an α-aminonitrile according
the cycle, substitution, addition, ring ex- to an ECEC mechanism (Scheme 12) [17].
pansion, ring contraction or ring opening. The oxidation of dithianes (Scheme 13)
leads to a dicationic species that reacts
12.1.2.1 Oxidation of Heterocycles with water affording aldehydes or ke-
The presence of electron-donating sub- tones and 1,2-dithiolane, which undergoes
stituents generally favors oxidation of further oxidation to the sulfoxide (20–74%
heterocycles. yields) [18].
H Me H Me Me Me
NC CN NC CN NC • CN NC CN
−e −H+ −e
•+ +
Me N Me Me N Me Me N Me Me N Me
Me Me Me Me
(80%)
Scheme 11 Anodic dehydrogenation of dihydropyridine.
−e −H+ −e
•+ •
+CN−
N N N N CN
C6H5 C6H5 C6H5 C6H5

(56%)
Scheme 12 Anodic cyanation of N-phenylpyridine.

+
R1 S −2e R1 S +H2O S
+ R1COR2
2 2 −H+ S
R S R S
+
R1 = H; R 2 = H, CH3, t-Bu, p-CH3OPh, Ph
R1 = CH3; R 2 = Ph
Scheme 13 Anodic deprotection of dithianes.
12.1.2.2 Reduction of Heterocycles bicyclic tetrahydrofurans produced from 3-

The presence of an electron-withdrawing cyclopentenyloxypropionates can be used
substituent can favor reductions of hete- as intermediates for the synthesis of
rocycles. In this way, the electroreduction prostaglandines.
of an activated thiopyran affords a dihy- Diarylamides with arenes activated by
drothiopyran with elimination of dimethy- electron-donating substituents can be con-
lamine (Scheme 14) [19]. verted to azacycles by anodic oxidation
through phenolic oxidative coupling re-
actions that can be a key step in the
12.2 synthesis of alkaloids (Schemes 16 and 17).
Oxidative Cyclizations at the Anode According to the nature of substituents
and the experimental conditions, either
12.2.1 spiro compounds [22] or non-spiro com-
Intramolecular Cyclizations pounds [23, 24] were obtained.
Carbon–carbon bond formation has also
12.2.1.1 Carbon–Carbon Bond Formation been achieved using electroauxiliaries.
The Kolbe electrolysis has been used by The method developed by Yoshida and
Schäfer and coworkers to synthetize sub- coworkers uses an auxiliary (silicon, tin,
stituted furans or pyrrolidines in good sulfur), which when added to a molecule,
yields by a carbon–carbon coupling reac- decreases the oxidation potential of the
tion after co-oxidations of 6-alkenoic acids starting compound. Thus the chance
and various carboxylic acids [4, 5, 20, 21] of overoxidation can be avoided. The
(Schemes 2 and 15). In Scheme 15, the anodic oxidation of compounds having a
MeO2C S MeO2C S
+2e + 2H+
MeO2C CO2Me MeO2C CO2Me

NMe2 NMe2
−NMe2
MeO2C S MeO2C S MeO2C S

+2e + 2H+ +
MeO2C CO2Me MeO2C CO2Me MeO2C CO2Me
(80–85%) (77–98%)
Scheme 14 Cathodic partial hydrogenation and deamination of a thiopyran.

12.2 Oxidative Cyclizations at the Anode 347
CO2− R2 R2
−e R3 R3
R2 + R3CO2− O + O
O −CO2
R1
R1 R1
R1 = H; R 2 = H; R 3 = CH3O2C(CH2)2; CH 3O2CCH2 (41–68%)
R1 = CH3CO2; R 2 = OEt; R 3 = CH3(CH2)7
Scheme 15 Intramolecular addition of Kolbe radicals.
OCH3 OCH3
H3CO CH3 H3CO CH3
N N
CH3CN NaClO4 (Pt)
1.1 VSCE
O O
H3CO H3CO
OCH3 OCH3
(45%)
Scheme 16 Anodic aryl–aryl coupling.
OCH3 OCH3
H3CO R1 H3CO
N
CH3CN HBF4 (Pt)
1.2 VSCE N COCF3
R1 = CF3CO; R 2 = H
R2
OCH3 O
(62%)
Scheme 17 Anodic aryl–aryl coupling.
carbon–carbon double bond leads to the A bromide was introduced in the

selective cleavage of the carbon–auxiliary reaction instead of a fluoride in performing
bond, and the effective intramolecular the anodic oxidation of α-stannyl ethers in
carbon–carbon bond formation leads to dibromomethane solvent with tetrabutyl-
one of the olefinic carbons and the ammonium perchlorate as the electrolyte
introduction of fluoride to the other in (Scheme 19) [28]. The bromide ion was
good yield (61–84%) (Scheme 18) [25–27]. generated by the reduction of the solvent
The stereoselectivity of the reaction at the cathode of an undivided cell.
is higher with a sulfur auxiliary Cyclizations involving aromatic rings
(cis/trans : 87/13) and lower with a silicon can also be obtained in good yield
auxiliary (cis/trans : 55/45). (54–80%) after anodic oxidations of
EA
O CH2Cl2 Bu4NBF4 (C anode) O O

+
Constant current
C7H15 C7H15 F C7H15 F
EA = SiMe3, SnBu3, SMe, SPh
Scheme 18 Selective anodic cyclization assisted by an electroauxiliary.
H H
O SnBu3 O
CH2Br2 Bu4NClO4 (C anode)
Constant current-undivided cell
H H
Br
(70%)
Scheme 19 Selective anodic cyclization assisted by an electroauxiliary.
α-stannyl ethers and carbamates [28] or α- media (methanol–KOH). A mixture of

organothiocarbamates [29] having an aro- two oxazolidines resulting from two N -
matic ring in the appropriate position alkyliminium intermediates was obtained.
(Scheme 20). The same mechanism can be pro-
posed for the intramolecular alkoxyla-
12.2.1.2 Carbon–Heteroatom Bond tion of conveniently substituted lactams
Formation (Scheme 21) [31, 32].
The oxidation of enol ethers at a
12.2.1.2.1 Carbon–Oxygen Bond For- reticulated vitreous carbon anode [2, 3]
mation Hydroxyl or carboxylate groups (Scheme 1) in a mixture of methanol/THF
can participate in a ring-closure reaction containing tetraethylammonium tosylate
by an intramolecular nucleophilic attack to as the electrolyte and 2,6-lutidine as the
a generated electrophilic center as already base leads to substituted tetrahydrofu-
described in Schemes 1 and 3. ran and tetrahydropyran rings in good
The process described in Scheme 3 was yields (51–96%). The major product ob-
previously observed by Weinberg and tained had a trans-stereochemistry. The cy-
coworker [30] for the anodic oxidation of clization failed to make seven-membered
N -benzyl,N -methylethanolamine in basic ring products. In order to determine the
EA
Y CH2Cl2 Bu4NClO4 (C anode) Y

Constant current
R R
EA = SnBu3; Y = O; R = H, F
EA = SnBu3; Y = NCO2CH3; R = H
EA = p-MeOC6H4S; Y = NCO2CH3; R = H
Scheme 20 Intramolecular cyclization to ethers and carbamates.

( )n ( )n
CH3CN H2O Et4NBF4
O N HO O N O
−2e − 2H+
n = 1 (74%)
n = 2 (63%)
Scheme 21 Intramolecular alkoxylation of lactams.
reactivity of a terminating group for the generates an N -acyliminium cation, which

enol ether radical cation, Moeller and is trapped by an intramolecular hy-
coworkers [2] used a cyclization reaction droxyl group, for oxidation of N -benzyl,N -
to form a five or six-membered ring and a methylethanolamine [30].
quaternary carbon (Scheme 22). The anodic oxidation of (S)-2-ace-
The reaction can also be initiated by tamido-2-(3,4-dimethoxybenzyl)propionit-
the oxidation of a ketene acetal equivalent rile (Scheme 25) [36] probably proceeds via
(Scheme 23). formation of a benzyl cation.
6,5-Bicyclic [33] and 7,5-bicyclic [34, 35] Substituted spiroketals can be pre-
dipeptides (Scheme 24) have been syn- pared in good yields (51–61%) by
thetized by a one-step electrochemi- the electrochemical oxidative cycliza-
cal cyclization from various dipeptides. tion of ω-hydroxytetrahydropyrans in
The selective anodic amide oxidation anhydrous ethanol containing lithium
MeO H
OMe Me OMe
30% MeOH/THF Et4NOTs
Me O Me
Me (RVC anode)
( )n H ( )n H
HO
H
n = 1 (74%) (3 : 1 mix of t/c isomers)
n = 2 (56%) (1 : 1 ratio of isomers)
Scheme 22 Cyclization of enolethers.
MeO TMS
OMe
OTs
Et 4N O
TMS H
MeO ode) CH2Ph
OMe C an
t id in e-(RV −1 )
2, 6-
lu mole (74%)
OH (2 F
CH2Ph
1-sa
me c O
ondit
ions OMe
(4 F
mole −1
2-H + )
O
CH2Ph
(69%)
Scheme 23 Cyclization of a ketene acetal equivalent.

H
OH O
( )n CH3CN Bu4NBF4 (Pt anode) ( )n
N Undivided cell-constant current N
Boc N Boc N
O CO2Me O CO2Me
H H
(n = 1, 2) n = 1 (15%)
n = 2 (48%)
Scheme 24 Cyclization of dipeptides.
H3C H3C CN
H Ar CN Ar H
H3C CN N N
CH3CO2H (CH3CO)2O O O
ArCH2 +
NHCOCH3 Anhydrous Na2CO3 (Pt anode)
CH3 CH3
Scheme 25 Cyclization of a benzyl cation.
R2 OH R2 O− R2
NaOEt −e
( )n ( )n H •
EtOH O
R1 O R1 O R1 O ( )n
R2 R2 R2
−e −H+
O
• OH OH
R1 O ( )n R1 O ( )n R1 O ( )n
+
n = 1; R 1 = C6H13, (C2H5)2CH; R 2 = H
n = 2; R 1 = (C2H5)2CH; R 2 = H, CH3
Scheme 26 Cyclization of ω-hydroxytetrahydropyrans .
tetafluoroborate as the electrolyte and The anodic lactonization of a 2-pipe-

sodium ethylate as the base [37]. The pro- ridinone carboxylic acid (Scheme 28) [39]
posed mechanism described in Scheme 26 results from a coupling reaction between
assumes, after a first-electron transfer, an the nucleophilic carboxylate and the elec-
intramolecular hydrogen abstraction fol- trogenerated iminium intermediate.
lowed by a second-electron transfer leading
to the selective formation of a cyclic oxo- 12.2.1.2.2 Carbon–Nitrogen Bond For-
nium cation. The process was completed mation A carbon–nitrogen bond can
by a subsequent cyclization. result either from the reaction between
The anodic oxidation of methyl-3,5- an anodically produced cationic center
dibromo-4-hydroxyphenylpyruvate oxime and an amino group or from the reac-
affords a spiroisooxazole in almost quanti- tion between a nucleophilic center and
tative yield (Scheme 27) [38]. an electrogenerated electrophilic nitrogen
CO2Me MeO2C
N
N
MeOH LiClO4 O
OH (C anode)
Br Br Br Br
OH O
Scheme 27 Cyclization to a spiroisooxazole.
C2H5 C2H5
CO2H −2e − 2H+ (Pt anode)
O
10% H2O/CH 3CN Et4NClO4
O N Undivided cell-constant current O N O
C2H5 C2H5
Scheme 28 Lactonization from an iminium intermediate.
obtained after oxidation of the amino or anodic oxidations of various phenylhydra-

the hydroxylamino groups. zones or equivalent species. In this way,
The oxidation of 8-t-butyl-1-(2-pyridyl)-2- electrochemical oxidations of benzylidene
naphthol illustrates the reaction between 2-pyridylhydrazone and chalcone phenyl-
a produced cationic center and a tertiary hydrazone [41–43] lead to 3-phenyl-s-
amine (Scheme 29) [40]. The produced triazolo[4,3a]pyridine (Scheme 30) and
pyridinium salt reacts in a basic medium 1,3,5-triphenylpyrazol (Scheme 31), re-
with loss of isobutylene. spectively.
Electrochemical syntheses of triazoles, Anodic oxidations of secondary amines
imidazoles, and pyrazoles can involve can provide radicals or radical cations.
N
t-Bu +N CiO4− +N
t-Bu
OH CH3CN NaClO4 O O−
KOH
Controlled potential-(Pt anode)
OAc OAc OAc

(40%)
Scheme 29 Intramolecular cyclization to a pyridinium salt.
N CH3CN Et4NClO4 N
N
Controlled potential-(C anode) N
N N
H Ph
Ph
(74%)
Scheme 30 Cyclization of a benzylidene 2-pyridylhydrazone.

Ph
Ph
CH3CN C5H5N
Ph
LiClO4 N Ph
N NH Ph N
Ph
(15–28%)
Scheme 31 Cyclization of phenylhydrazones.
THF R2 N
( − 10 °
Li C)
1-n-Bu LiClO 4 Ph
HM PA nt
2-THF t curre
onstan CH3
iv id e d cell-c ode)
R2 D (Pt an
NH Ph THF
CH3 O
H H2 O
Consta NaBF
R1 nt curr
ent-(P 4
t anod
e) R2 N
Ph
OCH3
Scheme 32 Cyclization of unsaturated amines.
In the presence of a double bond in an lower yields (38–42%) [44]. However, the
appropriate position, a radical coupling can presence of a methoxy group bonded
take place as shown in Scheme 32. to the nitrogen atom does not prevent
For R 1 = CH3 , the amines are first good yields as observed in Scheme 33,
treated with n-BuLi in order to generate where the product was isolated in 85%
the corresponding nitrogen anions, which yield [46].
undergo a one-electron oxidation, afford- Nitroso groups are well known as good
ing nitrogen radicals. After radical cou- electrophilic reagents and can be used to
pling followed by hydrogen abstraction prepare various heterocycles. However, a
from the solvent, pyrrolidines with a direct electrochemical access to nitroso
cis-stereochemistry are obtained in good derivatives from the corresponding nitro
yields (66–85%) [44, 45]. compounds is not usual. Generally, nitroso
For R 1 = OCH3 , the direct oxidation compounds are obtained in two consecu-
of the amines led to pyrrolidines in tive steps as summarized in Scheme 34.
OH
THF H2O NaBF4 X

Controlled potential-undivided cell
H3C NH graphite felt anode
H3C
OCH3 X = NOCH3
Scheme 33 Cyclization of O-methylhydroxylamines.

Cathodic reduction Anodic oxidation

ArNO2 ArNHOH ArNO
Scheme 34 Nitroso group generation by reduction – oxidation.
Electrosyntheses of heterocycles from Scheme 35 [47]. However, with electron-

nitroso derivatives prepared in a batch withdrawing substituents in β position
cell according to Scheme 34 need two (R 2 = CN or CO2 Et), only the azoxy
conditions. The first one is a good stability compound was obtained because of a slow
of the hydroxylamine intermediate and cyclization.
the second one is a very fast cyclization However, an improved electrochemi-
of the nitroso compound to avoid the cal ‘‘redox’’ methodology using a flow
formation of an azoxy compound by cell fitted with two consecutive porous
condensation of the generated nitroso electrodes of opposite polarities (cath-
and the hydroxylamine. Electroanalytical ode then anode), allows a rapid and
studies using cyclic voltammetry can give total oxidation at the anode of the hy-
information on the rate of cyclization. droxylamine intermediate produced at
Some N -hydroxyindoles were prepared the cathode. Various nitroso compounds
from o-nitrophenyl alkenes according to may be obtained in high yields without
R1 R2 R1 R2
4e + 4H+ − H2O
R3 R3
Ammoniacal buffer-ethanol
NO2 divided cell-controlled potential NHOH
(Hg cathode)
+
− 2H
−2e
R1 R2 R1
3
R
R2 (or R3)
NO N
R1 = R2 = H; R 3 = Ph OH
R1 = R3 = H; R 2 = CH3, C3H7;
Scheme 35 Cyclization of an electrogenerated nitroso compound.
(CH2)2 NHR Ammonium buffer-methanol (CH2)2 NHR

"Redox" electrolysis-constant current
NO2 (graphite felt electrodes) NO
−H2O
N Ring contraction N
N
R
OH NHR
R = n-C3H7, CH2Ph, CH(Ph)2, Ph, p-MeOPh
Scheme 36 Cyclization of an electrogenerated nitroso compound.

formation of azoxy compounds [48–54]. 12.2.1.3 Heteroatom–Heteroatom Bond

This methodology has been developed Formation
for the synthesis of 1-aminoindoles
(25–71% yields) from N-substituted 2- 12.2.1.3.1 Nitrogen–Nitrogen Bond For-
(ortho-nitrophenyl)ethylamines as depicted mation Triazole derivatives may be ob-
in Scheme 36 [53]. The intramolecular tained by the electrooxidation of molecules
cyclization involves hydrocinnoline-type containing several nitrogen atoms as illus-
intermediates that, under slightly basic trated in Scheme 39 [57].
conditions, undergo a spontaneous ring In order to prepare 2-substituted inda-
contraction. zoles, electrolyses (Scheme 40) of ortho-
Indirect oxidations of amides by electro- nitrobenzylamines in two steps were
generated ‘‘Cl+ ’’, which gives an adduct performed in a batch cell [7] and in a
with the amide nitrogen, has been flow cell, equipped with two consecutive
used to synthetize chiral building blocks porous electrodes of opposite polarities
(Scheme 37) [55]. (vide supra) [52]. Only benzylamines bear-
12.2.1.2.3 Carbon–Sulfur Bond Formation ing an electron-donating group were suc-
1,3-Thiazole derivatives can be obtained cessfully cyclized in a batch cell because an
in good yields (60–95%) by intramolecular electron-withdrawing substituent dramati-
electrocyclization of thiocarboximides. The cally decreased the rate of the intramolecu-
mechanism involving a two-electron pro- lar cyclization. On the contrary, indazoles
cess is shown in Scheme 38 [56]. After the substituted either by the electron-donating
second-electron transfer, the thiocarbonyl or the electron-withdrawing group were
group attacks the cationic site located in obtained in good yields (70–85%) in a
the ortho position of the aromatic nucleus. ‘‘redox’’ cell.
H CH3O
H
O CH3 O
CH 3OH CH3CN Et4NCl Ph N NH
N
Ph N OCH3 Undivided cell-(Pt anode)
O CH3 OH3C CO2CH3
H (84%)
Scheme 37 Cl-mediated cyclization of a dipeptide.
X X X S
S −e S −H+ − e − H+
•+
R
NH R NH R N
Scheme 38 Electrocyclization of a thiocarboximide.
NH N
CH3CN LiClO4
N N Controlled potential-(Pt anode) N N
Cl N OH Cl N
O
Scheme 39 Synthesis of a triazol.

CH2 NHR CH2 NHR

Acetate buffer-alcohol −H2O
N R
"Redox" electrolysis N
NO2 NO
R = H, CH3, C2H5, Ph, m-CH3Ph, p-CH3OPh, p-NCPh
Scheme 40 Cyclization by way of an electrogenerated NO-group.
In the same way, cinnoline and 1,4- or by the ‘‘dimerization’’ of the electrogen-
dihydrocinnoline were prepared from erated reagent (homocoupling reaction).
ortho-nitrophenyl ethylamine by a two-step
electrolysis performed either in a batch 12.2.2.1 Heterocoupling Reactions
cell [58] or in a flow cell [53] (Scheme 41).
12.2.2.1.1 Cycloaddition Reactions with
12.2.1.3.2Nitrogen–Oxygen Bond For- Alkenes Olefins can react with elec-
mation The anodic oxidation of vicinal trogenerated radicals, cationic species or
dioximes gives 3,4-diphenylfurazan-2- dienophiles.
oxide by intramolecular ring formation Electrochemical oxidations of anions
(Scheme 42) [59]. lead to radicals that may add to the
carbon–carbon double bonds. In this
12.2.2 way, the oxidation of anions of dimethyl
Intermolecular Coupling malonate or methyl acetylacetate in the
presence of olefines gives di- or tetrahy-
Intermolecular coupling reactions can take drofurans derivatives in moderate yields
place either through a reaction between (Scheme 43) [60].
an electrogenerated reagent and another The same reaction can occur during
suitable species (heterocoupling reaction) the anodic oxidation of the enolate of
NH2 NH2
Ammonium buffer-methanol
"Redox" electrolysis
NO2 NO
−H 2O
Oxidation
N N During work up N
N N N
H
(55%) (35%)
Scheme 41 Cinnolines via cyclization with an electrogenerated NO-group.
Ph Ph Ph Ph
CH3CN LiClO4
N N −e N N
O O
OH OH (74%)
Scheme 42 Anodic cyclization of vic-dioximes.

H3CO2C
PhCH CH2
(CH3O2C)2CH2 H3CO
CH3OH CH3ONa
H3CO Ph (40%)
−H+ − 2e + CH3O− (Pt anode) O
O
H3CO2C
H3C
H2C CHOC2H5
CH2 (36%)
Same medium
−H+ − 2e − H+ (Pt anode) H3C OC2H5
H3COC O
Scheme 43 Anodic addition of anions of 1,3-dicarbonyl compounds to electron-rich olefins.
O O
H 2C CHOC2H5
OC2H5
C2H5 OH C2H5ONa
O− −2e − H+ (Pt anode)
O
(57%)
Scheme 44 Anodic addition of the anion of a 1,3-dicarbonyl compound to vinyl ethyl ether.
cyclohexan-1,3-dione in a basic media reaction, first studied by Swenton and

(Scheme 44) [61, 62]. coworkers [65, 66], was recently performed
Yoshida and coworkers [63, 64] studied at a PTFE-coated carbon anode in a highly
the oxidative cycloaddition of cyclic 1,3- polar electrolyte solution affording dihy-
dione (1,3-cyclopentanedione and some drobenzofurans in good yields (60–99%)
1,3-cyclohexanediones) and olefins in var- (Scheme 47) [67].
ious solvents and electrolytes. The best re- The electrochemical oxidation of N ,N -
sults were obtained in acetonitrile contain- diarylhydrazines affords diazenium cat-
ing tetraethylammonium tosylate as elec- ions that undergo cycloadditions with
trolyte (97% yield with 5,5-dimethyl-1,3- olefins (vide supra Scheme 5) [8, 9, 68–70].
cyclohexadione and styrene) (Scheme 45). Acetonitrile can participate in the forma-
A mechanism involving attack of a tion of cycloadducts.
radical intermediate to olefin has been The electrochemical oxidation of
proposed (Scheme 46) [64]. N ,N -dibenzyl, N -arylhydrazines gives
An electrochemical oxidation of hydro- carbocations that react with alkenes
quinones can be used to initiate [3 + 2] affording five-membered heterocycles
cycloaddition reactions with alkenes. The (Scheme 48) [70].
O R3 O
CH2
R4 R3
R2 CH3CN Et4NOTs
R2 O R4
O −2e − 2H+
R2 R2
R1 Undivided cell (C anode) R1
R1 = R2 = H; R 4 = Ph R1 = R3 = H; R 2 = CH3; R 4 = Ph, CH2SiCH3

R1 = CH3; R 2 = R3 = H; R 4 = Ph R1 = H; R 2 = R3 = CH3; R 4 = OCH3, OCOCH3
Scheme 45 Anodic addition of the anion of 1,3-cyclohexanedione to electron rich olefins.

O O O O
R R
−e − H+ •
•
O HO O O
−e
O O O
R
−H+
R R +
O O + O
(50–80%) R = Ph, C(CH3) CH2, CH CH CH3
Scheme 46 Mechanism of anodic addition with subsequent cyclization.
R2
R1
OH R4 O
R1 R3
R R 3 R
R2 R4
CH3NO2 CH3CO2H LiClO4
Controlled potential
OCH3 (PTFE-fiber-coated glassy carbon anode) OCH3
R = H, COCH3; R 1 = R2 = R3 = CH3; R 4 = H
R = H; R 1 = R2 = R3 = R4 = CH3
R = H; R 1 = Ph; R 2 = R3 = R4 = H
OH O
O O
OCH3
Same conditions OCH3
OH
O
Scheme 47 Phenols in anodic addition with subsequent cyclization.
The anodic oxidation of N -methylamides The coupling reaction is very fast be-
leads to N -acyliminium intermediates that cause unstable cyclopentadienols resulting
may react with olefins (Scheme 49) [71]. from the decomposition of ferrocenium
Dienophilic cyclic α-carbonylazo com- cations can be trapped, in good yields
pounds (triazoline diones, indazolone, (80%), by triazoline diones [73]. The cy-
phthalazine dione) prepared in a flow cloadduct is obtained with totally regio and
cell, by anodic oxidation of the corre- stereo selectivities (Scheme 51).
sponding hydrazino compounds in acidic The oxidative addition of N ,N -
methanol or acetonitrile, react with dienes dimethylurea to 2,4-hexadiene gives
(Scheme 50) [72, 73]. imidazolinones (Scheme 52) [74].
H3C CH3
RCH2 RCH2 H3C CH3 N

R N Ar
CH3CN LiClO4
N NHAr N NHAr −H+
−2e − H+ (Pt anode)
CH2R
RCH2 RCH Ar
+
R = H, Ph CH2R
−H+ N N
Ar = 2,4-(NO2)Ph
Scheme 48 Cycloaddition with N,N-dibenzylhydrazines.
R3
R1 R1 R1 +
R2 CH3CN LiClO4 R2 + Ph N
N N R3
−2e − H+ (Pt anode)
O O R2 O Ph
CH3 CH2
R1 = CH3; R2= H; R3= Ph (45–61%)
R1 = R2 = CH3; R 3 = Ph
R1 = R3 = H; R 2 = CH3
Scheme 49 Cycloaddition with N-acyliminium ions.
( )n O
HN NH N N ( )n
CH3CN H2SO4 R
O −2e − 2H+-constant current O N N
O N O N N
(Graphite felt anode) O
R R (43–87%)
n = 1, 2; R = CH3, Ph, m-CH3Ph
Scheme 50 Cycloaddition with hydrazino compounds.
HN NH R N N R
CH3CN H2SO4
Fe+
O + O +
Fe
O N (Graphite felt anode) O N
R R
Ph 3 Ph
O
a 2C
dN
R oli
OH ,s
O2
O
N R = H, CH3, C2H5
N
N Ph
O
Scheme 51 Anodic cycloaddition of a hydrazino compound to cyclopentadiene from ferrocene.

H3C H3C
+(CH3NH)2CO ; (CH 3CN NaClO4)
N N + N N
−2e − 2H+ H3C C CH3 H3C C CH3
Constant current (C anode)
O O
(20%) (20%)
Scheme 52 Anodic addition of dimethylurea to 2,4-hexadiene.
12.2.2.1.2 Cycloaddition Reactions with nitrobenzenes react with sulfinic acids

Other Nucleophiles The anodic two- affording N -sulfonylated hydroxylamines
electron oxidation of catechol affords o- that may undergo cyclization into N -
quinone that may react with the enolates sulfonylated benzisoxazolones in moder-
of 4-hydroxycoumarine or 5,5-dimethyl- ate yields (50–79%) (Scheme 55) [49–51].
1,3-cyclohexanedione (dimedone). The re-
sulting adducts undergo a second an- 12.2.2.2 Homocoupling Reactions
odic oxidation leading to benzofuran Anodic dimerizations of enamino esters
derivatives in good yields (90–95%) (Scheme 56) or ketones may give symmet-
(Scheme 53) [75, 76]. rically substituted pyrroles [78].
The oxidation of N -phenylhydrazones in Dimerizations can also be observed from
the presence of pyridine leads to the forma- the anodic oxidations of ketene imines
tion of s-triazolo[4,3a]pyridinium salts by (Scheme 57) [79] or alkylisothiocyanates
attack of pyridine as a nucleophile on the (Scheme 58) [80].
nitrilimine intermediate (Scheme 54) [77]. Derivatives of dihydrofurans are pro-
Conveniently, ortho-substituted nitroso- duced in limited yields (20–37%) af-
benzenes prepared in a ‘‘redox’’ cell ter the anodic oxidations of phenols
(vide supra) from the corresponding (Scheme 59) [81].
OH
OH
OH O
O O OH
H2O CH3CO2Na
OH −4e − 4H+-undivided cell
Controlled potential-( anode)
O O
Scheme 53 Anodic cycloaddition with catechol.
−2e − 2H+ − +
ArNH N CHAr′ ArN N CAr′
CH3CN Et4NClO4
Controlled potential (C anode)
Ar′ Ar′
N N −2e − 2H+
N
Ar N N Ar N N+
H
Scheme 54 Anodic cycloaddition between pyridine and N-phenylhydrazones.

OH O
COR1 COR1 O
NO N N
+R2SO2H SO2R2 −R1H SO2R2
R1 = OH, OCH3; R 2 = C6H5, 4-CH3C6H4, camphoryl
Scheme 55 Cycloaddition with electrogenerated nitrosobenzenes.
H3CO2C CO2CH3
PhCH2NH H CH3OH NaClO4
H3C CH3
H3C CO2CH3 N
CH2Ph
(45%)
Scheme 56 Anodic dimerization of enamino esters.
Ph N
Ph X
CH2Cl2 Bu4NClO4
p-XC6H4N C CPh2 N
Controlled potential (Pt anode)
Ph
X Ph
x = H, CH3, OCH3
(12–70%)
Scheme 57 Anodic coupling of ketenimines.
R O
S S N S
CH3CN LiClO4
RN C S O + S
Controlled potential (Pt anode) RN S N
R = CH3, C2H5, n-C3H7, n-C4H9 R
R
(30–40%)
Scheme 58 Anodic coupling of alkylisothiocyanates.
OH
R R
R R R
CH3CN H2O Et4NBF4
O
R R
O
R R
R = H, CH3, C2H5 (20–37%)
Scheme 59 Dihydrofurans by anodic coupling of phenols.

12.3 Reductive Cyclization at the Cathode 361
12.3 pyridinium salts N-substituted by a non-

Reductive Cyclization at the Cathode conjugated keto group (Scheme 62) [85],
afford cyclic tertiary alcohols.
12.3.1
The cathodic cleavage of dihalides may
Intramolecular Cyclization
be a powerful route to a variety of
12.3.1.1 Carbon–Carbon Bond Formation heterocycles (Schemes 63 and 64) [86–88].
Electrohydrodimerization is well known Organic electroreductive coupling reac-
for its application in the preparation of tions using transition-metal complexes as
adiponitrile [82]. The method was suc- catalysts have been widely investigated.
cessfully used in the preparation of Reviews on the subject have been pub-
heterocycles from reductions of acti- lished [89, 90]. The method involving the
vated bis-alkenes (Scheme 60 and vide most common transition-metal complexes
supra Scheme 6) [10, 83] or bis-imines af- (nickel, cobalt, palladium) appears to be a
fording substituted piperazines in good useful tool to synthetize heterocycles from
yields, in the presence of proton donors organic halides via radical intermediates.
(Scheme 61) [84]. Nickel catalyst precursors are nickel(II)
Reductive cyclizations of nonconjugated salts that are cathodically reduced either to
olefinic ketones (see Scheme 8) [12] or nickel(I) or to nickel(0) and cobalt catalyst
O O CH2CO2C2H5
CH CHCO2C2H5 CH3CN H2O Et4NOTs
CH CHCO2C2H5 2e + 2H+
O O CH2CO2C2H5
(89%)
Scheme 60 Cathodic cyclization of activated bis-alkenes.
H
R1 N R2 R1 N R2
DMF MsOH
2e + 2H+ (Pb cathode)
R1 N R2 R1 N R2
H
R1 = C6H5, p-CH3OC6H4, o-HOC6H4; R 2 = H (38–95%)
R1 = o-HOC6H4; R 2, R2 = (CH2)4
Scheme 61 Cathodic cyclization of activated bis-imines.
R3 R3 R3
R2 R4 R2 R4 R2 R4
H2O H2SO4
H + H
+ O 4e + 4H+ (Hg cathode) OH OH
R1 N R1 N R1 N
Constant current
R1 = R2 = R3 = R4 = H
R1 = CH3; R 2 = R3 = R4 = H (40–62%)
R1 = R3 = R4 = H; R 2 = CH3,…
Scheme 62 Cathodic cyclization of N-ketoalkyl pyridinium salts.

p-MeOC6H4 CO2Et
DMF TEAClO4
N Br CO2Et
(Hg cathode) N
Br CO2Et O
O CO2Et C6H4OMe-p
(85%)
Scheme 63 β-Lactams by cathodic elimination of dihalides.
Ph
Ph S Ph S
2e 2Br− S S
+
Br Br DMF TEAClO4 Ph Ph
(Hg cathode) Ph S Ph
44% 2%
Scheme 64 Trithiacyclohexane by cathodic elimination of α,α’-dibromothioether .
precursors are cobalt(III) or cobalt(II) the carbon–metal bond regenerates the

that are reduced to cobalt(I). Phosphino active form of the catalyst and gives an
complexes of palladium(II) undergo a two- alkyl, alkenyl, or aryl radical, which adds
electron reduction to active palladium(0). intramolecularly to a double or a triple
The reduced complexes react rapidly with bond. In some cases, a carbanion is ob-
insertion in the carbon–halogen bond of tained, which can react with electrophiles.
the organic substrate, and simultaneous Some examples are given below.
oxidation of the metallic center. After a Catalytic electroreductions involving nic-
second electron transfer, the cleavage of kel complexes produced five [91–95] or
R2
R1 R3
X
R1 DMF Ni(cyclam) 2+ (10%)
( )m
O R2 Undivided cell-constant current
( )nO
( )n ( )m (Mg anode, carbon fiber cathode)
R3
X = Cl, Br, I R1, R2 = H, CH3 (40–90%)
n = 0, 1 R3 = H, CH3, alkyl, homoallyl
m = 1,2
Scheme 65 Heterocycles by Nickel catalyzed intramolecular cathodic addition of halides to
double bonds.
C2H5O O C2H5O O
DMF NH4ClO4 Et4NClO4 Ni(cyclam)2+
H
Divided cell-controlled potential
Br R1 (C cathode) R1
H
R2 R2
R1 = H, C2H5, Ph (16–88%)
R2 = H; CO 2CH3, SPh
double bonds.
R2 R2
R3 Br R3
DMF Ni(CR)2+
O O
N N
R1 R1 = H, Ts, allyl, benzyl R1

R2, R3 = H, CH3 (49–67%)
double bonds.
six-membered [96, 97] rings in low to high Palladium complexes have been
yields from conveniently available unsatu- used for the electroreductive cycliza-
rated halides (Schemes 65, 66 and 67). tion of N -alkenyl-2-bromoanilines to
Similar cyclizations can be performed the corresponding indoline derivatives
using cobalt complexes (vitamin B12 (Scheme 69) [101]. The postulated carban-
and B12 analogs) as mediators [97–100] ion intermediate undergoes a reaction with
(Scheme 68). the electrophiles (H+ , CO2 ).
R
R
Br MeOH Et4NOTs cobaloxime
Undivided cell (Zn anode and cathode)
O O O O
R = H, C5H11
(35–84%)
Scheme 68 Vitamin B12 -catalyzed cyclization of alkyl bromides with alkynes.
R R
R PdBr −
PdBr
2e − Br−
N N N
CO2Et CO2Et CO2Et

Pd(0) +E+
R
R E
Br
R = H, Ph
E+ = H+, CO2
N N
CO2Et CO2Et
(67–81%)
Scheme 69 Palladium(0) catalyzed cathodic cyclization of aryl bromides and double bonds.
12.3.1.2 Carbon–Heteroatom Bond hydroxylamino groups (four-electron re-

Formation duction) or amino groups (six-electron
reduction, in a sufficiently acidic medium,
12.3.1.2.1 Carbon–Oxygen Bond Forma- at a more negative potential than the first
tion The cathodic reduction of some four-electron wave). In the presence of a
nitrocarbonyl compounds in aqueous suitable electrophilic substituent (keto, es-
acidic medium gives the hydroxylamino
ter or cyano group), a cyclization can occur
derivatives that can undergo a ring-closure
with a carbon–nitrogen bond formation
reaction affording anthranilic compounds
leading to the heterocyclic N -hydroxy com-
or isoxazolones [102–104] (Schemes 70
pounds, N-oxides or hydroxamic acids.
and 71).
In acidic or slightly basic aqueous media,
Butenolides can be produced af-
ter cathodic reduction involving an N -hydroxyindoles can be prepared after
electron-deficient allene and a ketone electrolysis of α-(o-nitrophenyl) ketones
(Scheme 72) [105]. (vide supra Scheme 9) [13], at a working
potential corresponding to the first ca-
Carbon–Nitrogen Bond Forma-
12.3.1.2.2 thodic wave. In an acidic medium, indoles
tion The cathodic reduction, in protic are directly obtained at a working poten-
media, of aromatic nitro compounds tial corresponding to the second cathodic
produces nucleophilic centers, either wave.
−H 2O O
COR COR H 3) N
H, C
4e + 4H+ (R =
O
−H2O −RH
NO2 NHOH (
R=O O
H, O
CH ,
3 NH N
2)
Scheme 70 Cathodic reduction of nitrocarbonyl compounds to anthranilic derivatives.
Ph
Ph O
CH CONH2 4e + 4H+
Me Me
Controlled potential O
C NO2 (Hg cathode) Me N
Me
H
Scheme 71 Cathodic reduction of nitrocarbonyl compounds to isoxazolones.
O
n-Bu
O O Bu-n
CO2Me DMF Et4NOTs
C
Divided cell-constant current
(C cathode)
Scheme 72 Butenolides by cathodic cyclization of allene and ketone.

Electrochemical reductions of several prepared after a cathodic reduction

ortho-substituted nitro compounds of of o-nitrophenoxy and o-nitrophenylthio-
the general formula o-O2 NC6 H4 CH = acetic compounds, respectively (Sche-
CR1 R2 (Scheme 73) [47, 106, 107] or o- me 75) [109–111].
O2 NC6 H4 COCHR1 R2 (Scheme 74) [108], A benzothiazine derivative can be also
in which R 1 and R 2 are electron- obtained after a four-electron reduction of
withdrawing substituents, have been per- an o-nitrobenzyl thiocyanate in an acidic
formed in acidic media leading to various medium (Scheme 76) [112].
quinoline derivatives. The cathodic reduction of substi-
2-H -1,4-Benzoxazine and 2-H -1,4- tuted nitrophenylpyridines, pyridiniums
benzothiazine derivatives have been or dihydropyridines gives naphthyridine
R2
R1 = R2 = CO2H, CO2Et N O
R2 OH
4e + 4H+ − H2O
CH C
R1 Divided cell (Hg cathode) R2
NO2
R1 = CN; R 2 = H, CN, CONH2 N R3
R1 = R2 = COCH3
O
R1 = COPh; R 2 = CO2Et
R3 = NH2
R1 = COPh; R 2 = CN
R3 = CH3
R3 = Ph
R3 = Ph
Scheme 73 Cyclization of o-substituted nitroaryl compounds.
R1 = R2 = COCH3 OH OH
R1 = COCH3; R 2 = COC6H5 R2 R1
R1 = COC6H5; R 2 = CN +
O N R3 N R3
R1
CH 4e + 4H+ − H2O O O
Controlled potential R3 = CH3
NO2 R2 Divided cell R3 = CH3 R3 = C6H5
(Hg cathode)
OH OH
R1 R2
+
R1 = CO2CH3; R 2 = COCH3 N R3 N O
R1 = CO2Et; R 2 = CN
O OH
R3 = CH3
R3 = NH2
Scheme 74 Cyclization of o-substituted nitroaryl compounds.

X CH2CO2R X
4e + 4H+
NO2 Divided cell (Hg cathode) N O
X = O, S
OH
R = H, CH3
Scheme 75 Benzoxazines and benzothiazines by cathodic cyclization.
CH2SCN
4e + 4H+ S
NO2 N NH2
Scheme 76 Benzothiazine by cathodic cyclization of o-nitrobenzylthiocyanate.
OH
N
MeO2C
O
e
2M
Me N Me
O
C
=
NO2 4e + 4H+
R
R R Controlled potential
R
=
(Hg cathode)
C
N
O
Me N Me
N
NC
NH2
Me N Me
Scheme 77 Naphthyridines by cathodic cyclization.
derivatives in good yields (Schemes 77 and The electrochemical reduction of the

78) [113–115]. corresponding nitrophenylpyridine or
The four-electron reduction of sym- pyridinium derivatives only produces
metrical (R 2 = CN; Scheme 78) [114] or cyclic hydroxamic acids.
unsymmetrical (R 2 = CO2 Me) [115] 4-(o- In the same way, a benzodiazepine ring
nitrophenyl)-1,4-dihydropyridines leads to can be obtained after cathodic reduction
aminobenzonaphthyridine N-oxide when of an anodically cyanated 2-nitrobenzyl
the electrolysis is performed in slightly tetrahydroquinoline (Scheme 79) [115].
acidic or slightly basic medium; in higher According to the working potential,
basic medium, the reduction of the un- the medium, and the nature of
symmetrical compound gives a cyclic hy- substituents, the cathodic reduction of
droxamic acid. aliphatic γ -nitroketones leads to pyrroline
O
(Hg cathode) N
pH 4.5 (R1 = H)
R2
pH 9 (R1 = Me; R 2 = CO2Me) NH2
(63–83%)
Me N Me
NO2
R1
NC R 4e + 4H+
OH
Me N Me
N
R1 NC
O (47%)
R1 =H R2 = CN, CO2Me Flow cell
Me N Me
(Graphite felt cathode)
R1 = Me R2 = CO2Me pH 11 (R2 = CO2Me)
R1
Scheme 78 Naphthyridines by cathodic cyclization.
4e + 4H+ N
N Controlled potential N
(Hg cathode) O
NO2 CN NH2
(60%)
Scheme 79 Cathodic cyclization to the benzodiazepine ring.
N-oxide, pyrrolines, and pyrrolidines 12.3.2

(Scheme 80) [116, 117]. Intermolecular Cyclization
In the same way, the four-
electron cathodic reduction of γ - 12.3.2.1 Heterocoupling Reactions
nitroesters gives N -hydroxypyrrolidinones The electrochemical reduction of 2,2-
(Scheme 81) [118]. dibromo-1,3-diones in the presence of
various olefins (styrene, indene) affords
the [3 + 2] cycloadducts, 2,3-dihydrofuran
12.3.1.3 Heteroatom–Heteroatom Bond derivatives in moderate to good yields
Formation (37–94%) (Scheme 84) [124].
The cathodic reduction of 2-bromo-
12.3.1.3.1 Nitrogen–Nitrogen Bond For- 2-nitropropane in the presence of
mation The cathodic reduction of dimethyl acetylene dicarboxylate leads
o-nitroazobenzenes in a basic medium to 5,5-dimethyl-2,3,4-trimethoxycarbonyl-
leads to benzotriazole N-oxides (Sche- 5-hydropyrrole as the major product (64%
me 82) [119–121]. yield) (Scheme 85) [125].
2,2 -Dinitrobiphenyl, in an alkaline so- The reduction of acrylic ester in
lution, is reduced to benzo[c]cinnoline the presence of aldehydes or ketones
N-oxide (Scheme 83) [122, 123]. and trimethylsilyl chloride affords
Ph
R1
R2 N R3
r
ffe
4H
bu
+
O
m
4e
Ph
iu
Ph
on
m
6e + 6H+
Am
R1 R3 R1
R2O2N O (Hg cathode) Sulfuric acid
R2 N Me
8e ate
(R = Me)
Ac
et
+ bu
R3 = Ph, Me Ph
8H ffe
+
r R1
R3 N R3
Scheme 80 N-Heterocycles by cathodic reduction of γ -nitroketones.
Ph Ph
R1 4e + 4H+ R1
OMe
R3 N O
R2 O2N O Controlled potential
(Hg cathode)
R1 = R2 = H OH
R1 = R2 = Me
R1 = H; R 2 = Me
Scheme 81 N-Heterocycles by cathodic reduction of γ -nitroesters.
R2
R2
N N R1 N
2e + 2H+ N R1
Controlled potential N
NO2 (Hg cathode)
R1 = R2 = H O
R1 = OH; R 2 = H
R1 = Me; R 2 = OH
Scheme 82 Benzotriazoles by cathodic cyclization.
6e + 6H+
Controlled potential N N
O2N NO2 (Hg cathode)
O
Scheme 83 Benzo[c]cinnoline by cathodic cyclization of 2,2’-dinitrobiphenyl.

12.4 Anodic Oxidation of Heterocycles 369
O R4 O
Br
R3 CH CH R4
Br R1 DMF ET4NOTs R3 R1
Constant current O
O R2 (Pt cathode) R2
R1 = H; R 2 = Me
R1 = R2 = Me
Scheme 84 [3 + 2]-Cycloaddition with 2,2-dibromo-1,3-diones and alkenes.
Me
MeO2C CO2Me
Me C NO2 MeO 2 C C C CO2 Me
CH2Cl2 Bu4NBF4 Me
N CO2Me
Br Controlled potential (Hg cathode) Me
(64%)
Scheme 85 Cathodic cycloaddition of 2-bromo-2-nitropropane to dimethyl acetylenedicarboxylate.
R1
Me3SiCl
H2C CHCO2CH3 + C O R1
DMF Et4NOTs O
R2 Constant current R2 O
(Pb cathode)
Scheme 86 Cathodic heterocoupling of ketones with methyl acrylate.
MeO
OMe
N O
MeO MeO CO2Me MeO
DMF Et4NOTs
+ OMe
N+ Controlled potential
MeO CH2Br (Pt cathode)
H
(100%) OMe
Scheme 87 Alkaloid-type compounds by reductive alkylation of iminium salts.
5-substituted tetrahydrofuran-2-one in 12.4

moderate to good yields (51–86%) Anodic Oxidation of Heterocycles
(Scheme 86) [126].
12.4.1
The electroreduction of iminium salts in
Double Bond Formation
the presence of alkyl halides has been app-
lied to the synthesis of alkaloid-type comp- The formation of a double bond during
ounds as depicted in Scheme 87 [127, 128]. anodic oxidations can result from elimina-
tions of protons, carbon dioxide or acylium
12.3.2.2 Homocoupling Reaction cations. The electrooxidative aromatization
The cathodic reduction of phenyl of dihydropyridine derivatives and het-
bromide in an aprotic medium gives erocycles containing nitrogen atom (di-
substituted furan as summarized in hydroquinoxalines, tetrahydrocinnolines)
Scheme 88 [129–133]. involves an ECE mechanism as previously
+ PhCOCH2Br Ph
PhCOCH2Br 2e Br− PhCOCH2−
DMF LiClO4 −H2O
(Hg cathode) O Ph
(80%)
Scheme 88 Cathodic cyclization of a α-bromoketone to a furan.
R4
R2 R3
(60–92%)
R4
+
R2 R3 H ) Me N Me
− 2e −2 = H
1 R4
(R
(R 1 −H R2 R3
Me N Me +
=
H) (60–85%)
+
R1 Me N Me
R1 = H; R 2 = R3 = CN
R1 = R4 = Me; R 2 = R3 = CN R1
R1 = H, Me; R 2 = R3 = CO2Me; R 4 = o-O2NC6H4
R1 = H, Me; R 2 = R3 = CN; R 4 = o-O2NC6H4
R1 = H, Me; R 2 = CN; R 3 = CO2Me; R 4 = o-O2NC6H4
Scheme 89 Anodic dehydrogenation of dihydropyridines.
Ph Ph
Me Me
N CH3CN Et4NClO4 collidine N
N N
Ph Controlled potential (Pt anode) Ph
Ph Ph
(65%)
Scheme 90 Anodic dehydrogenation of pyrazolines.
depicted in Scheme 11. The anodic oxi- The anodic oxidation of 1,4-diphenyl-
dation of substituted 1,4-dihydropyridines 1,2,3,4-tetrahydrocinnoline, leads to the
can be performed in acetonitrile, at a plat- corresponding 1,4-dihydrocinnoline and
inum anode [16, 134] or in slightly acidic cinnolinium salt, at a more anodic po-
hydroalcoholic media, at a graphite felt tential (Scheme 91) [8].
anode in a flow cell (Scheme 89) [113, 114]. The electrooxidation of N ,N -diacetyldi-
The electrooxidation of substituted pyra- hydroquinoxaline involves a cleavage of
zolines in the presence of a base (pyridine, the nitrogen–acylcarbon bonds according
collidine), which facilitates deprotonation to an ECEC mechanism (Scheme 92) [139].
from the pyrazoline ring, gives the cor- The anodic oxidation of 2,5-dihydro-
responding pyrazoles (Scheme 90). In the 1H -1-benzazepines in slightly acidic
absence of a base, an Ar–Ar coupling prod- hydroalcoholic medium gives 5H -
uct is obtained [135–138]. 1-benzazepines in moderate yields
Ph Ph Ph
+
N N N
NH CH3CN LiClO4 N −2e − 2H+ N
−2e − 2H+ 1.0 V (Ag/Ag +)
0.4 V (Ag/Ag +) (Pt anode)
Ph Ph Ph
Scheme 91 Anodic dehydrogenation of tetrahydrocinnoline.
COCH3
N N
DMF LiClO4
+
−2e − 2CH3CO
N Controlled potential N
(Pt anode)
COCH3 (66%)
Scheme 92 Anodic deacylation of N, N−diacetyldihydroquinoxaline to quinoxaline.
R2 H H R2 H H
−2e − 2H+
R3 R1 R1
Constant current R3
N Me Flow cell (graphite felt anode) N
H Me
H
R1 = R2 = Me; R 3 = H, 6-Me, 9-Me, 7-F
R1 = Me; R 2 = H; R 3 = H, 7-F
R1 = Et; R 2 = R3 = H
Scheme 93 Anodic dehydrogenation of dihydrobenzazepine.
CO2H
Pyridine H2O Et3N
O O
(Pt anode)
O O
(95%)
Scheme 94 Dehydrogenation by way of anodic decarboxylation.
(35–45%) (Scheme 93) [140]. In a electrodecarboxylation corresponding to a

slightly basic medium, an intermolecular discharge of a carboxylate ion as shown
coupling reaction is observed (vide infra in Scheme 94 [141], or by an indirect
Scheme 128). electrodecarboxylation involving the oxi-
The formation of a double bond dation of a heteroatom in the β-position
can also be performed either by direct (Scheme 95) [142–144].
R1 R1
CO2H THF H2O KOH
N R2 (C anode) N R2
COCH3 COCH3
R1 = Ph; R 2 = H, CO2C2H5 (86–94%)
R1 = Me; R 2 = H, CO2C2H5
Scheme 95 Dehydrogenation–decarboxylation to pyrroles.
Various intermediates (uracil, thymine, the anodic methoxylation or cyanation

pyrazoline, β-carboline, and dihydro- of heterocycles can produce powerful
quinoline derivatives) have been prepared synthons.
in this way [142–147].
12.4.2.1 Methoxylation Reactions
12.4.2 Anodic oxidations of heteroaromatic cycles
Functionalization of Heterocycles (furans, pyrroles, benzofurans) in the pres-
ence of methanol have been extensively
The anodic functionalization of hetero- studied [148–165]. The electromethoxyla-
cycles, which generally results from a tion of differently substituted furans gives
nucleophilic attack of reagents to the ox- 2,5-dimethoxy-2,5-dihydrofurans in mod-
idized heterocycle, is of great interest in erate to good yields (Scheme 96) [148–159,
synthetic organic chemistry. In particular, 166–170].
R3 R4 R3 R4
MeOH electrolyte
MeO OMe
−2e (Pt anode)
R1 O R2 R1 O R2
Scheme 96 Anodic methoxylation of furan.
R2 R2 OMe
MeOH H2SO4 R1
R1 OMe
(C anode)
O O
R1 = =H
R2 (44–86%)
R1 = H, CO2Et; R 2 = Me
R1 = Ph; R 2 = H
Scheme 97 Anodic methoxylation of benzofuran.
MeOH KOH MeO OMe

N −2e-constant current MeO N OMe
(Pt anode)
Me Me
Scheme 98 Anodic tetramethoxylation of N-methylpyrrol.

n MeOH Et4NOTs n
Undivided cell OMe

N N
(C anode)
CO2CH3 CO2CH3
n = 1, 2 (75–78%)
Scheme 99 Anodic methoxylation via an iminium cation.
CH2Cl2 Bu4NClO4 NuH

−74 °C (C anode) Nu
N N+ or NuTMS N
CO2Me CO2Me CO2Me
Scheme 100 Preparation of stable iminium carbamates at low temperature and trapping with
nucleophiles.
In a similar way, benzofurans and N - In addition to this method, Yoshida and

methylpyrrole afford 2,3-dimethoxylated coworkers [183] have electrochemically
derivatives (Scheme 97) [160] and 2,5-tetra- prepared, at low temperatures, stable
methoxy-2,5-dihydro-N -methylpyrrole, re- N-substituted cations (Scheme 100) that
spectively (Scheme 98) [57, 161, 162]. can directly react with various nucleophiles
A nucleophilic attack of methanol after electrolysis.
in the α-position to a nitrogen atom Using this method, a first trapping of the
can take place through an electrochem- iminium cation with methanol followed by
ically generated iminium cation from a regeneration of this cation with a Lewis
substituted pyrrolidine [171, 172], piperi- acid is avoided.
dine [173–180] or oxazolidinone [181, 182] The electrodecarboxylation of heterocy-
derivatives, as illustrated in Scheme 99 for cles having a carboxylic group in α-position
N -carbomethoxypyrrolidine [163] and N - to an heteroatom (oxygen, nitrogen) can
lead to the corresponding methoxylated
carbomethoxypiperidine [174].
product when the electrolysis is performed
The corresponding methoxylated pro-
in methanol [143, 184–189], as shown in
ducts are equivalents of iminium cations
Scheme 101.
and consequently, can be very versa-
tile synthetic intermediates that can un- 12.4.2.2 Acetoxylation Reactions
dergo a substitution of the methoxylated The electroacetoxylation of furan proceeds
group by nucleophiles under Lewis acid in a way similar to electromethoxylation
conditions. (Scheme 102) [190], but by a different
MeOH MeONa
O N CO2H (C anode) O N OMe
R R
R = H, C4H9 (38–41%)
Scheme 101 Methoxylation via anodic decarboxylation.

CH3CN CH3CO2H CH3CO2Na

(Pt anode) AcO OAc
O O
(57%)
Scheme 102 Anodic nuclear diacetoxylation of furan.
CH3CN CH3CO2H CH3CO2Na

AcO OAc
Me O Me (Pt anode) O
Scheme 103 Anodic side chain diacetoxylation of furan.
R2 R2 OAc
CH3CO2H DBU R1
R1 Controlled potential
N OAc
N (Pt anode)
COCH3 COCH3
(76–82%)
Scheme 104 Anodic diacetoxylation of an indole derivative.
C2H5
C2H5
CO2H
CH3CN H2 O Et4NCIO4 O
O N Undivided cell-constant current O N O
(Pt anode)
C2H5 C2H5
Scheme 105 γ -Lactone by intramolecular acyloxylation.
method for 2,5-dimethylfuran for which an Lactones can be produced by in-

acetoxylation of the side chain is observed tramolecular acetoxylation of piperidine
(Scheme 103) [170]. (Scheme 105) [177].
The anodic diacetoxylation of N -acety- A monoacetoxylation may be obtained
lindoles (or N -acetylindoline) in acetic acid via an electrodecarboxylation of hete-
and in the presence of a base affords rocycles (β-lactam [193, 194] or oxazo-
the corresponding 2,3-diacetoxyindoline lidine derivatives [195]) having a car-
(Scheme 104) [191]. A 2,3-diacetoxylation boxylic group in α-position, as shown
of N -carbomethoxypiperidine is also ob- in Scheme 106 for the preparation of 4-
served [192]. acetoxy-2-azetidinones.
CO2H OAc
CH3CN CH3CO2H Bu4NBF4
NH Undivided cell NH
O (Pt anode) O
(76%)
Scheme 106 Decarboxylative acetoxylation of a β-lactam.

R R R R
CH3CN H2O NaHCO3
LiBF4-constant current HO OH
O (Pt anode) O
R = Et, AcO, CH 2Cl, … (70–86%)
Scheme 107 Anodic dihydroxylation of furan.
Ph Ph
Ph (60%)
Ph Ph R=H
Ph N OH
CH3CN Et4NClO4
Ph N Ph (Pt anode) Ph Ph
Ph
R R = Me Ph N+ OH
R = H, Me
R
Scheme 108 2-Hydroxylation of pyrrole.
12.4.2.3 Hydroxylation Reactions 12.4.2.4 Cyanation Reactions

A 2,5-dihydroxylation can be obtained α-Aminonitrile derivatives can be prepared
by anodic oxidation of furan derivatives by anodic oxidations of N-substituted
under suitable experimental conditions tertiary cyclic amines (pyrrolidines [204],
(Scheme 107) [149, 196]. piperidines [17, 115, 204–208], tetrahydro-
Anodic oxidations of 2,3,4,5-tetra- quinolines [17, 115, 205–207], tetrahydro-
phenylpyrrole in an organic solvent isoquinolines [206], azepane, morpholine,
(nitromethane, acetonitrile) containing thiomorpholine, piperazine [207], ben-
trace amounts of water afford 2-hydroxy zazepines [115]), in the presence of cyanide
derivatives (Scheme 108) [197–199]. ions as depicted in Scheme 12 for N -
The electrohydroxylation of tetrahydro- phenylpiperidine and Scheme 109 for N -
furan [200, 201] and N -carbomethoxypyr- alkyltetrahydroquinolines [17].
rolidine [202, 203], in the presence of The anodic cyanation of N -alkyl tertiary
water, gives the corresponding 2-hydroxy cyclic amines can give a mixture of
derivatives. regioisomers as observed in Scheme 109.
CH 3 OH CH 3 CO2 Li NaCN
+
Flow cell (graphite felt anode)
N N CN N
CH2R CH2R CHR

NC
R = H, Me, Ph, o,m,p-O2NPh (35–65%) (5–15%)
Scheme 109 Cyanation of tetrahydroquinoline.

CH3OH CH3CO2Li
NaCN-constant current
N SiMe3 Flow cell (graphite felt anode)
N CN
CH2Ph CH2Ph
(75%)
Scheme 110 Regioselective α-cyanation of piperidine by replacement of a trimethylsilyl group.
The problem of regioselectivity can be 2. lowers the oxidation potential of tertiary

avoided by using a trimethylsilyl group amines compared to non-silylated
in the α-position to the nitrogen atom species.
(Scheme 110) of N -benzyltetrahydroqui-
Anodic cyanations of N-substituted
noline and piperidine derivatives [205].
pyrrole or 2-methylpyrrole derivatives
The trimethylsilyl group
take place in the α-position to the
nitrogen atom (Scheme 111) [209] and
1. directs the iminium formation through at the side chain with 2,5-dimethyl
a preferential desilylation reaction ver- or 2,3,4,5-tetramethylpyrrole derivatives
sus deprotonation; and (Scheme 112).
CH3OH NaCN
R2 N Controlled potential R2 N CN
Divided cell (Pt anode)
R1 R1
R1= Me, Ph
(60–82%)
R = H, Me
2
Scheme 111 Nuclear cyanation of pyrrole.
R2 R2 R2 R2
CH3OH NaCN
H3C CH3 Controlled potential H3C CH2CN
N N
R1 R1
R1 = Me, Ph (29–67%)
R2 = H, Me
Scheme 112 Side-chain cyanation of pyrrole.
Ph Ph
CH3CN Et4NCN Ph Ph
Ph Ph Controlled potential NC N CN
N
(Pt anode)
Ph Ph
Scheme 113 1,4-Addition of cyanide to pyrrole.

R3
R3 CN
R2 = H N
CH3OH NaCN
R2
N (16–77%) R1
R1
R1 = R2 = H; R 3 = Me CN
R1 = Me; R 2 = R3 = H
R1 = R3 = Me; R 2 = H R2
R2 = Me; R 3 = H
R1 = R2 = Me; R 3 = H N
(45%) R1
Scheme 114 Nuclear cyanation of indole.
However, a dicyanation can be obser- fluoride anions lead to a deprotonation

ved for 1,2,3,5-tetraphenylpyrrole leading at the α carbon, followed by addition of
to 1,2,3,5-tetraphenyl-2,5-dicyanopyrroline a fluoride ion to the intermediate cation
(Scheme 113) [210]. (Scheme 115) [211].
In contrast, the cyanation of the side In a similar way, a monofluorination
chain is not observed for indole derivatives of various phenylthio derivatives of lac-
(Scheme 114) [209]. tams [212, 213], lactones [214] and diox-
olanones [215] was achieved.
12.4.2.5 Halogenation Reactions A monofluorination of 2-substituted-
Anodic oxidations of thioethers such as 3- 1,3-oxathiolan-5-ones (Scheme 116) [216],
phenylthiooxindole derivatives (n = 0) or 2-substituted dithiolanones [217], thi-
3-oxo-4-phenylthiotetrahydroisoquinoline azolidinones [218], and dihydrochro-
derivatives (n = 1) in the presence of manone or thiodihydrochromanone
SPh F SPh
R1 O R1 O
CH3CN Me4NF, 4 HF (Et 4NF, 3 HF)
N Undivided cell-constant current N
n R2 (Pt anode) n R2
(50–71%)
n = 0 R1 = H; R 2 = Ph
n = 0 R1 = Me; R 2 = p. CH3Ph
n = 1 R1 = H; R 2 = Ph, PhCH2
Scheme 115 Monofluorination of tetrahydroisoquinoline.
S CH3CN Et4NF, 4 HF F S
R Controlled potential R
O O (Pt anode) O O
R = Et, n.Pr, i.Pr, Ph, p. NCPh (66−86%)
Scheme 116 Monofluorination of oxathiolanone.

derivatives [219–221] occurs at the posi- derivatives [223] takes place at the posi-
tion α to the heteroatom. tion β to the heteroatom as shown in
In contrast, the anodic fluorination Scheme 117.
of α,β-unsaturated cyclic heterocycles The regioselective electrohalomethoxy-
such as flavone [222] or thioflavone lation of chromone derivatives is followed
O O
CH3CN Et3N, 3 HF
F
Undivided cell-controlled potential
S Ph S Ph
(46%)
Scheme 117 β-Monofluorination of a thioflavone.
OMe
O R2 H2O O R2 O R2
KX CH3OH R1 = H
R1 (graphite anode) R1 X
X
O O O
R1 = R2 = H; X = Cl, Br (70%, 86%) (92%, 93%)

R1 = H; R 2 = Me; X = Cl, Br (97%, 92%) (90%, 95%)
R1,R2 = −(CH2)3−; X = Cl (61%)
R1,R2 = −(CH2)4−; X = Cl (73%)
Scheme 118 Halomethoxylation of chromene.
O O
F3C
CH3CN H2O NaOH
NEt + CF3CO2H NEt
F3C
O O
(44%)
Scheme 119 Trifluoromethylation by anodic decarboxylation of trifluoroacetic acid in the presence of
double bonds.
OR2
4
R O R 3O
CH3CN LiClO4 NaHCO3
N
MeO Divided cell-controlled potential
R1 (or CH3CN HBF4-undivided cell)
OR2 (Pt anode)
N R1
OR3 R 4O
O (43–93%)
R1 = H, CH3; R 2 = R3 = R4 = CH3
R1 = R2 = R4= CH3; R 3 = CH2Ph
R1 = R3 = R4 = CH3; R 2 = CH2Ph, CH3CO
R1 = R2 = R3 = CH3; R 4 = CH2Ph
Scheme 120 Intramolecular coupling of 1-benzyltetrahydroisoquinolines.

in some cases by a demethoxylation A similar intramolecular coupling

to afford chloro and bromochromones is observed for isochroman analogs
(Scheme 118) [224]. of 1-benzylisoquinoline alkaloids (Sche-
me 121) [234].
Intramolecular anodic olefin coupling
12.4.2.6 Trifluoromethylation Reactions reactions involving heteroatomic aromatic
The anodic oxidation of trifluoroacetic rings were used to prepare fused, bicyclic
acid affords the trifluoromethyl radical ring skeletons (Scheme 122) [159].
CF•3 . Addition of this radical to
unsaturated heterocycles can pro-
12.4.2.8 Dimerization Reactions
duce bis(trifluoromethylated) compounds
Anodic oxidations of heterocycles can
(Scheme 119) [225].
produce symmetrical dimers via car-
bon–carbon coupling.
12.4.2.7 Intramolecular Coupling The anodic dimerization of 1,2,3,5-
Reactions tetraphenylpyrrole occurs at the C-3 po-
The anodic oxidation of 1-benzyltetrahy- sition (Scheme 123) [210].
droisoquinoline derivatives produces 5,5 -Substituted hydurilic acids can be
morphinandienones according to Sche- obtained from 5-substituted barbituric
me 120 [81, 226–233]. acids as shown in Scheme 124 [159].
OMe
MeO
MeO
CH3CN HBF4
O
MeO Undivided cell-controlled potential R
R (Pt anode)
OMe O
MeO
OMe
O
R = H (16%)
R = CH3 (56%)
Scheme 121 Intramolecular coupling of isochromane and aryl.
n n n
MeOH CH2Cl2
H+
LiClO4 -2,6-lutidine
O MeO O
2 Constant current O
R R2 R2
(RVC anode)
R1 MeO R1 MeO R1
n = 1 R1 = SMe, OMe, Ph; R 2 = H (54−75%)
n = 1 R1 = R2 = CH3 (24%)
n = 2 R1 = OMe, Ph; R 2 = H (41−62%)
n = 2 R1 = R2 = CH3 (48%)
n = 3 R1 = OMe; R 2 = H (32%)
Scheme 122 Intramolecular coupling of furan and alkene.

Ph Ph Ph
Ph Ph
CH3CN LiClO4
Ph Ph Controlled potential N N
N
(Pt anode) Ph Ph
Ph Ph
Ph
Scheme 123 Anodic dimerization of pyrrole.
R2 R2 R2
O N O O N O O N O
H2O (pH 1)
N H Controlled potential N N
R3 R3R3
R1 (Pyrolytic graphite anode) R1 R1
O O O
R1 = R2 = H; R 3 = C2H5, CH2Ph (44–64%)
R1 = Me; R 2 = H; R 3 = C2H5 (61%)
R1 = R2 = Me; R 3 = Me, C2H5 (68–69%)
R1 = R2 = Me; R 2 = H (67%)
Scheme 124 Anodic dimerization of barbituric acid.
S CH3CN Bu4NBF4 S S
S (Pt anode) S S
(40%)
Scheme 125 Anodic dimerization of dithioles to tetrathiofulvalene.
R S R
R S R
CH3CN Et4NBF4 N
H
Controlled potential N
N
H
R = C(CH3)3, Cl, SCN, NO2 R S R
(70–80%)
Scheme 126 Unsymmetrical dimer by anodic coupling of a phenothiazine.
CH3CN H2O LiClO4 N

H N
(Graphite felt anode)
N
H
(98%)
Scheme 127 Unsymmetrical dimer by anodic coupling of a tetrahydrocarbazole.

Tetrathiafulvalenes can be produced by produce conducting polymer films coat-

an oxidative electrodimerization of 1,3- ing the electrode (Scheme 129). A review
dithiole derivatives (Scheme 125) [235]. of electropolymerized films is summarized
Unsymmetrical dimers may also be elec- in Refs. [237, 238], also see Chapter 16.
trochemically produced as illustrated in
Schemes 126, 127, and 128 respectively, 12.4.3
from phenothiazine derivatives [236], tetra- Ring Expansions
hydrocarbazole [146] and dihydrobenzaze-
pine derivatives [140]. Anodic decarboxylations of β-carboxylate
In addition, anodic oxidations, at a ethylene acetals afford 2-methoxy-1,4-
platinum or glassy carbon electrode, dioxan derivatives.
of heterocycles such as pyrrole or The mechanism involves a rearrange-
thiophene derivatives in organic sol- ment of the electrogenerated cation
vents (acetonitrile, propylene carbonate, with an expansion of heterocycles
dichloromethane) were widely used to (Scheme 130) [239, 240].
R1
R2 H H CH3 R2 H H
H H
Ammoniacal buffer H
R1 N R1
Flow cell-constant current R2
N CH3 (Graphite felt anode) N CH3
H
H
R1 = R2 = CH3 (50%)
R1 = CH3, C2H5; R 2 = H (25–28%)
Scheme 128 Unsymmetrical dimer by anodic coupling of a dihydrobenzazepine.
y+
−(2n + 2) e − (2n + 2) H+ X
(n + 2) , yA−
X −ye + yA− X X
n
X = S, NR ;
A− = ClO4−, BF4−, PF6−, …
Scheme 129 Anodic polymerization of pyrrole and thiophene.
O R1 −2e − CO2 O R1
R2 R2
MeOH KOH +
O CO−2 Undivided cell-constant current
O
R3 R3
(Graphite anode)
R1 = Me, Et Rearrangement
R2 = H, Me, Et
O + R1 O OMe
R3 = H, Me, Et +MeO− R12
R2 R
O R3 O R3
(40–62%)
Scheme 130 Rearrangement of electrogenerated cation.

CH2Ph
N
Less than 0.3 e
PhCH2 N PhCH2 N N CH2Ph
MeOH (or CH2Cl2) Bu4NClO4
Divided cell-controlled potential N
(Pt anode)
CH2Ph
(60–80%)
Scheme 131 Tetramerization of benzylaziridine.
A particular ring expansion cor- 12.5

responding to a tetramerization of Cathodic Reduction of Heterocycles
1-benzylaziridine may be induced anod-
12.5.1
ically leading to a tetraazacyclododecane
Electroreductive Hydrogenation of Double
(Scheme 131) [241]. Bonds
However, it is worth noting that anodic
oxidations of aziridine derivatives can give The hydrogenation of a double bond
a mixture of opened compounds [242]. during cathodic reductions generally re-
sults from addition of protons to an
12.4.4 electrogenerated basic species. It is
Ring Contractions worth noting that partial and selective
hydrogenation can take place according
As previously illustrated in Scheme 13, to the nature of the heterocycles and the
the anodic oxidation of dithianes experimental conditions.
involves a ring contraction affording 1,2- The electroreduction of deactivated
dithiolane [18]. pyridines or pyridinium salts affords
selectively the corresponding 1,2- or
1,4-dihydropyridine derivatives according
12.4.5 to the position of the substituents
Ring Opening (Schemes 133 and 134) [243]. In the same
experimental conditions a monoactivated
As an example, a convenient preparation of pyridine is not reducible.
methyl (E) and (Z)-4,4-dimethoxybutenoa- N -Methyl and N -benzylpyridinium salts
tes can be performed by anodic oxidation of in an aqueous acidic medium (HCl), can
furfuryl alcohol, furfural or furoic acid via a be reduced, at high current densities, into
dimethoxylated dihydrofuran intermediate N -methyl and N -benzylpyridines in good
(Scheme 132) [157]. yields (87–98%) [244].
−4e
MeO CO2Me
O R CH3OH Et4NClO4
Constant current OMe
(Pt anode) (75–87%)
R = CH2OH, CHO, CO 2H
Scheme 132 Ring opening of furan derivatives.

12.5 Cathodic Reduction of Heterocycles 383
H H
N CO2Me +2e + 2H+ N CO2Me N CO2Me
MeOH Et4NOTs NH4Cl
or
CO2Me Divided cell-constant current CO2Me CO2Me
(Pt cathode)
(2, 4-, 2, 6- and 3, (2, 3- and 2,
4-disubstituted) 5-disubstituted)
(67–92%) (77–83%)
Scheme 133 Cathodic hydrogenation of pyridine.
R R
N+ N
+2e + H+
MeOH Et4NOTs NH4Cl
CO2Me CO2Me
CO2Me (Pt cathode) CO2Me
R = Me, CH2Ph (80–87%)
Scheme 134 Cathodic hydrogenation of pyridinium salt.
The electrochemical reduction of pyraz- Similar behaviors were observed for

ines in an alkaline hydroorganic medium quinoxaline [246, 247] and pyridopyrazine
gives the corresponding 1,4-dihydropyraz- derivatives [248, 249].
ines that are easily reoxidizable. Generally, Triazines are reducible in two 2-e steps
1,4-dihydropyrazines isomerize into 1,2- or in slightly acidic media [250]. The first
1,6-dihydropyrazines (Scheme 135) [245]. reduction leads to a mixture of two
H H
N Ph +2e + 2H+
N Ph N Ph
Rearrangement
CH3OH H2O NaOH
N Ph Divided cell-controlled potential N Ph N Ph
(Hg cathode) H
Scheme 135 Cathodic hydrogenation of pyrazines.
H
Ph N Ph N
NH N
+
CN .6)
Ph N Ph Ph N Ph
CH 3 (pH 3 H
Ph N f fe r (23%) (63%)
N +2e + 2H+ bu
rate
Cit
Divided cell-controlled potential CH
Ph N Ph 3 CN
(Hg cathode) Na
OH Ph N
N
Ph N Ph
H
(80%)
Scheme 136 Cathodic hydrogenation of a triazine.

dihydro compounds (Scheme 136). A ring The electroreductive hydrogenation of

contraction is observed at a more cathodic pyridazine-3-ones performed at the first
potential (vide infra Scheme 160). wave, in acidic or basic medium, takes
Only one isomer is produced in good place at the 4,5-double bond. A fur-
yields (80%) in a basic medium. The ther reduction of 4,5- dihydropyridazin-
latter is further reducible in a slightly 3-ones in basic media, affords the cor-
acidic medium in the tetrahydro derivative responding tetrahydro derivatives (Sch-
(Scheme 137). eme 139) [252].
Triazine-3-ones and triazine-3-thiones A ring contraction (vide infra
can also be reduced in two consecutive Scheme 161) or a ring opening of
steps leading to the corresponding dihy- electrogenerated tetrahydro derivatives can
dro and tetrahydro derivatives. However, be observed in sulfuric acid.
according to the experimental conditions, The cathodic reduction of 4-carboethoxy-
a ring contraction can occur at the second coumarin in the presence of a catalytic
step [250]. amount of various chiral alkaloids
The electrochemical reductions of pur- can afford 4-carboethoxydihydrocoumarin
ine, adenine, and related compounds in low enantiomeric excess (ee ≤
involve two consecutive steps as shown 20%) (Scheme 140) [253]. In the
in Scheme 138 for adenine [251]. case of 4-methyldihydrocoumarine, the
H
Ph N Ph N
N +2e + 2H+ N
CH3CN-citrate buffer (pH 3.6)
Ph N Ph Divided cell-controlled potential Ph N Ph
H (Hg cathode) H
(45%)
Scheme 137 Cathodic hydrogenation of a dihydrotriazine.
NH2 NH2 NH2

N +2e + 2H+ HN N +2e + 2H+ HN N
N
Aqueous buffer
N N N N N N
H Controlled potential-(Hg cathode) H H
H
Scheme 138 Cathodic hydrogenation of adenine.
O O O
R1 +2e + 2H+
R1
R4 R1 +2e + 2H+ R4 R4
N N N
H2SO4 (or ammoniacal buffer) Ammoniacal buffer
N N -ethanol NH
R3 -ethanol R3 R3
R2 Divided cell-controlled potential R2 R2
(Hg cathode)
(80%) (50–75%)
R1 = R3 = R4 = H; R 2 = Ph
R1 = R2 = R4 = H; R 3 = Ph
R1 = R4 = Me; R 3 = H; R 2 = Ph
Scheme 139 Cathodic hydrogenation of pyridazine-3-one.

CO2Et CO2Et
+2e + 2H+ *
Acidic aqueous buffer-ethanol
O O Divided cell-controlled potential O O
(Hg cathode)
Scheme 140 Enantioselective cathodic hydrogenation of coumarine in the presence of an alkaloid.
enantio-selectivity has been increased to steps. An electrolysis carried out at the

67% ee [254]. plateau of the first wave yields the
Monoactivated and diactivated sub- 5,6-dihydro compounds. The tetrahydro
stituted 6H -1,3-thiazines can be re- derivatives can be prepared at more
duced in a slightly acidic hydroorganic cathodic potentials (Scheme 142).
medium [255–258]. In the case of thi- 2-Ethoxy-4H -1,3-thiazines bearing an
azines monoactivated at carbon 5, an NMe2 substituent at carbon 4 are reducible
electrolysis performed at the plateau of in two 2-e steps in slightly basic media.
the two-electron wave gives the 2,3-dihydro An electroreduction performed at the first
compounds (Scheme 141). wave is followed by a dimethylamine
2-Phenylthiazines diactivated at C-4 and elimination (Scheme 143) [259, 260]. The
C-5 positions are reducible in two 2-e electrolysis carried out at the second
R1 S R1 S
+2e + 2H+
N Acetate buffer-ethanol HN
R3 Divided cell-controlled potential
R3
R2 (Hg cathode) R2
R1 = Ph; R 2 = H, Me; R 3 = CHO, COMe (60–75%)
R1 = SPh; R 2 = H; R 3 = COMe
Scheme 141 Partial hydrogenation of a thiazine.
Ph S Ph S Ph S
+2e + 2H+ +2e + 2H+
N Acetate buffer-ethanol N (R = COMe) HN
R R COMe
CO2Et (Hg cathode) CO2Et CO2Et
R = CHO, COMe (75–80%) (75%)
Scheme 142 Partial and full hydrogenation of a thiazine.
EtO S CO2Me +2e + 2H+

EtO S CO2Me
Ammoniacal buffer-ethanol + Me2NH

CO2Me Divided cell-controlled potential CO2Me
R NMe2 (Hg cathode)
R
R = H, Me (83–90%)
Scheme 143 Hydrogenation and elimination of a thiazine.

wave involves a ring opening (vide in the presence of aliphatic chlorides,

infra Scheme 167). A ring contraction is bromides or iodides leads to the for-
observed in acidic medium (vide infra mation of 2,4,6-triaryl-4-alkyl-4H -pyrans
Scheme 162). (Scheme 144) [262].
Functionalized dihydrothiopyran deriva- A mixture of 2,4,6-triphenyl-4-(4-bromo-
tives can be obtained by electroreduction butyl)-4H -pyran (28%) and 1,4-bis-(2,4,6-
of triactivated [19] (vide supra Scheme 14) triphenyl-4H -pyranyl)-butane (6%) is ob-
and tetraactivated 4H -thiopyrans [261]. tained when 1,4-dibromobutane is used as
the electrophile.
12.5.2 The electroreduction of oxazolinium
Functionalization of Heterocycles salts gives acylanion equivalents that react
in a Michael addition with activated
The cathodic reduction of heterocycles
olefins as shown for methylacrylate in
generally affords nucleophilic species that
Scheme 145 [263].
can react with electrophilic reagents.
The cathodic reduction of quinoxaline
or 4-methylcinnoline in the presence
Addition Reactions
12.5.2.1 of acetic anhydride affords diacetylated
The two-electronic cathodic reduction products [264] as depicted in Scheme 146
of some 2,4,6-triarylpyrylium cations for quinoxaline.
Ph Ph Ph R
−
+2e +RX
+ Divided cell-controlled potential −X−
Ph O Ph (Hg cathode) Ph O Ph Ph O Ph
(11–68%)
RX = MeI, EtBr, n-BuCl, PhCH2Cl, Br(CH2)3Br, Br(CH 2)4Br
Scheme 144 Cathodic alkylation of triarylpyrilium cations.
O +2e O Ph(CH2)2 O
− CO2Me
Ph(CH2)2 + Ph(CH2)2
DMF Et4NOTs
N N N
Me3SiCl
(Pb cathode) MeO2C
Me Me Me
(68%)
Scheme 145 Cathodic Michael addition of an oxazolinium salt.
Ac
N N
+2e + 2Ac2O
+ CH3CO2−
DMF Bu4NI
N (Hg cathode) N
Ac
(92%)
Scheme 146 Cathodic diacetylation of quinoxaline.

A tetraacetylation with cleavage of the The electroreductive coupling process

N−N bond can take place as observed for can also been performed with heteroaryl
3,6-diphenylpyridazine(Scheme 147) halides as 2- or 3-bromothiophene or 3-
A monoacetoxylation of 2,3-diphenyl- bromofuran instead of aryl halides.
pyrido[3,4b]pyrazine at position 5 has been In a similar way, 2-arylpyrimidines and
observed (Scheme 148) [249]. 2-arylpyrazines have been prepared from
However, 3-Phenylpyrido[3,4b]pyrazine 2-chloropyrimidine and 2-chloropyrazine
in acetonitrile can be diacetylated at the and various functionalized aryl halides. An
1,4-positions in low yields (19%). iron anode is used in order to generate
iron salts that allow the desired coupling
12.5.2.2 Substitution Reactions reaction (Scheme 150) [267].
2-Arylpyridines can be obtained by 4-Phenylquinoline derivatives can also
the electrochemical reduction of the be prepared by an electrochemical
corresponding aryl and pyridyl halides cross-coupling of functionalized phenyl
using a sacrificial anode (Mg, Zn or Fe) halides with 4-chloroquinoline derivatives
in the presence of NiBr2 bpy as a catalyst in the presence of a cobalt catalyst
(Scheme 149) [265, 266]. (Scheme 151) [268].
Ph Ph Ph
N +2e + 2Ac2O NAc +2e + 2Ac2O NAc2

N DMF Bu4NI NAc NAc2
(Hg cathode)
Ph Ph Ph
Scheme 147 Cathodic tetraacetylation of diphenylpyridazine.
Ph N Ph N
+2e + Ac2O
CH3CN (DMF)
Ph N N Divided cell-controlled potential Ph N N
(Hg cathode)
Ac
(CH3CN: 91%; DMF: 26 %)
Scheme 148 Monoacetylation of pyridopyrazine.
X R2
R2
DMF Bu4NBF4
+ R1
R1 NiBr2bpy 13% N
N Y Undivided cell
Constant current
(30–80%)
(Ni cathode)
X, Y = Br or Cl
R1, R2 = electron-donating or electron-withdrawing groups
Scheme 149 Cathodic heterocoupling of aryl halides and pyridyl halides.

X
N
N DMF pyridine Bu4NBF4 R
+ N
R FeBr2 NiBr2bpy 13%
N Cl Undivided cell
Constant current
(Fe anode; Ni cathode) (31–77%)
R = 4-CO2Et, 4-COMe, 4-CF3, 4-CN, 2-CN, 4-Cl; X = Br

R = 4-OMe; X = I
Scheme 150 Cathodic heterocoupling of aryl halide and pyrimidine halide.
R1
X Cl
CH3CN DMF pyridine Bu4NBF4
CoCl2 0.26 eq.
R1 + Undivided cell-constant current
N R2 (Fe anode; stainless steel cathode)
N R2
R1 = 4-CO2Et, 3-CO2Et, 4-OMe, 4-Me; R 2 = Me
(48–81%)
R1 = 3-CO2Et; R 2 = H, Ph
Scheme 151 Cathodic heterocoupling of aryl halide and chloroquinoline.
12.5.2.3 Intramolecular Coupling pyridinium salts lead to quinolizidine

Reactions (vide supra Scheme 62) and indolizidine
An electrochemical synthesis of apor- derivatives [85].
phines via cathodic cyclization of iodo
benzylisoquinolinium salts has been re-
ported(Scheme 152) [269]. 12.5.2.4 Dimerization Reactions
Diastereoselective cathodic cyclizations Cathodic reductions of 1-substituted-
of 1-(4-oxoalkyl) and 1-(3-oxoalkyl) 3-nicotinamides (1-methylnicotinamide,
+
N N
CH3CN Et4NBr
I Me Me
Divided cell-controlled potential R
(Hg cathode)
R
R
R R = H, OMe (74–86%)
Scheme 152 Aporphine by cathodic cyclization of a iodobenzylisoquinolinium salt.
O O O
NH2 H2N NH2

DMSO
+
N Divided cell-controlled potential N N
(Hg cathode)
R R R
Scheme 153 Cathodic dimerization of nicotinamide.

NAD+ , NMN+ , NADP+ ) in nonaqueous position with consumption of 3 F mol−1 .

media (acetonitrile, DMSO) involve An intermediate resulting from reduction
1 F mol−1 to form neutral free of the N−OH bond has been postulated
radicals that dimerize at the 6-position (Scheme 154) [107].
(Scheme 153) [270]. The electrochemical behavior of this
Anodic oxidations of the dimers produce intermediate and that of coumarin deriva-
the dehydrodimers. tives can be similar [271–273], as shown
The cathodic dimerization of 1-hydroxy- in Scheme 155 for 3-carboethoxy-
3-carbethoxy-2-quinolone occurs at the C-4 coumarin.
N O
CO2Et CO2Et
+2e + 2H+ (e + H+)
CO2Et
Acetate buffer-ethanol
N O divided cell N O EtO2C
OH (Hg cathode) H O N
Scheme 154 Cathodic dimerization of a quinolone.
O O
CO2Et
+2e + 2H+
CO2Et
Aqueous buffer-ethanol
O O EtO2C
(Hg cathode)
O O
Scheme 155 Cathodic dimerization of a coumarine.
R1 R1
R2
O O
R2
R2
R3 R3
(+e + H+)
R = R = Ph; R = H
1 3 2
CH3CN Et4NClO4
+ R1 = R2 = R3 = Me
R3 O R1
(Hg)
R2 R1
MeO
OMe
R1 R2
R1 = R2 = Ph, p-MePh
Scheme 156 Cathodic dimerization of pyrylium salts.

An asymmetric induction can be per- When the cathodic reduction of 2-

formed during the cathodic reduction phenyl-6H -1,3-thiazines monoactivated at
of various substituted coumarins in the the C-5 position is carried out at the
presence of chiral alkaloids. A mixture foot of the first wave, hydrodimers
of dimers and dihydrocoumarins is ob- resulting from coupling at the C-2 posi-
tained in various yields according to the tion were obtained in relatively good yields
nature of the alkaloids (31–89% of dimer (Scheme 158) [255, 256].
and 5–67% of dihydrocoumarin with
unsubstituted coumarin) [273]. 12.5.3
Bipyrans can be prepared by quantitative Ring Expansions
cathodic reductions of the correspond-
The electrochemical reduction of vari-
ing pyrylium and benzopyrylium salts.
ous bicyclic α-amino ketones such as
According to the nature of the substituents,
quinolizidinone (n = 2) (Scheme 159) can
dimerizations obtained from pyrylium
involve a cleavage of the carbon–nitrogen
salts take place at the C-2 or C-4 positions
bond giving a ring enlargement [275, 276].
(Scheme 156) [274].
The major compound obtained from the 12.5.4
electrolysis of 3-phenyl-2H -1,4-benzoxa- Ring Contractions
zine results from a 1-e reductive dimer-
ization with the coupling taking place at A ring contraction can be obtained by het-
the C-3 position (Scheme 157) [109]. eroatom (sulfur, nitrogen) extrusion from
O
O + Ph
(e + H ) H
N N
Acetate buffer-ethanol H
N Ph Divided cell-controlled potential Ph
(hg cathode) O
(50%)
Scheme 157 Cathodic dimerization of benzoxazines.
Ph Ph
Ph S S S
(e + H+)
N R Acetate buffer-ethanol R NH NH R
O (Hg cathode) O O
R = H, Me (70–80%)
Scheme 158 Cathodic dimerization of thiazines.
O OH
H2SO4 30%
60 °C
n H n
N Constant current N
(Pb cathode)
n = 1–4
Scheme 159 Cathodic ring expansion.

heterocycles. The first process generally Activated pyrroles can be prepared by

involves a ring opening. the cathodic reduction of 4H -1,3-thiazines
Electrolyses at the second reduction step (Scheme 162) [259, 260] or pyridazines
of triazine derivatives in acidic medium, (Scheme 163) [277].
can produce substituted imidazole deriva-
tives as illustrated in Scheme 160 for 12.5.5
2,4,5-triphenylimidazole [250]. Ring Opening
The cathodic reduction in acidic
medium, of 4,5-dihydropyridazine-3-ones The cathodic reduction of cyclic quater-
unsubstituted at the N-2 position gives nary ammonium compounds can involve
1-aminopyrrolidin-2-ones via the cor- a cleavage at the N atom with ring
responding tetrahydropyridazine-3-ones. opening as observed for anilinium salts
4,5-Dihydropyridazine-3-ones substituted (Scheme 164) [244].
at the N-2 position afford pyrolin-2-ones The electrochemical reduction of het-
derivatives [252] (Scheme 161). erocyclic enammonium salts can give
Ph Ph
Ph N +4e + 4H+
N N NH + NH3
CH3CN-citrate buffer (pH 3.6)
Ph N Ph Ph
(80%)
Scheme 160 Cathodic ring contraction.
R3 R2
O R4 N O
R1 +2e + 2H+ H
R2 R
1 =
N H2SO4-ethanol
R1 NH2
N Divided cell =
R3 Controlled potential
M
e
CH3
R4 (Hg cathode)
Ph O
R1 = R2 = R3 = H; R 4 = Ph N
R1 = R2 = R4 = H; R 3 = Ph
R1 = R2 = Me; R 3 = H; R 4 = Ph Me
R1 S CO2Me MeO2C CO2Me

+4e + 4H+
N H2SO4-ethanol
CO2Me R1 N R2
2
R NMe2 (Hg cathode)
H
R1 = OEt, Ph; R 2 = H, CO2 Et (40–88%)

CO2Me
N +4e + 4H+
N Acetate buffer-ethanol MeO2C N CO2Me
CO2Me (Hg cathode)
H
(60%)
(CH2)n +2e + 2H+ (CH2)n NMe2

+
N (Hg cathode)
Me Me (88–90%)
n = 2–4
Scheme 164 Ring opening of anilinium salts.
a mixture of products in different 2,3-diaryl-2H -tetrazolium-5-thiolate com-

yields depending on the pH value pounds (Scheme 166) [279].
(Scheme 165) [278]. The four-electronic cathodic reduc-
A N−N bond cleavage can be obtained by tion of 4-H -1,3-thiazine derivatives in a
the cathodic reduction of some mesoionic slightly basic medium leads to a ring
1
+ R
NH
CN
O O R2
H2
CN + + (0–93%)
+2e + 2H+ +H
+ CN Aqueous buffer 1 +2
N R e
+
divided cell N 2H
+
R 2 (Hg cathode)
R 1 R2
R1 N
NC
R2
(0–82%)
Scheme 165 Ring opening of enammonium salts.
Ar Ar
ArNH NAr ArNH NHAr
N N +2e + 2H+ +2e + 3H+
N NH N N HN NH
Divided cell
_ controlled potential _
S S SH
Scheme 166 Cathodic N–N bond cleavage.

R1 S CO2Me R1 S CO2Me
+4e + 4H+
N Ammoniacal buffer-ethanol HN
CO2Me Divided cell-controlled potential CO2Me
R2 NMe2 (Hg cathode) R2
R1 = OEt, Ph; R 2 = H, Me (44–89%)
Scheme 167 Cathodic C–S bond cleavage.
opening by cleavage of a C−S bond 19. D. Rondeau, E. Raoult, A. Tallec et al., Elec-
(Scheme 167) [260]. trochim. Acta 1997, 42, 2185.
20. L. Becking, H. J. Schäfer, Tetrahedron Lett.
1988, 29, 2801.
References 21. J. Weiguny, H. J. Schäfer, Liebigs Ann.
Chem. 1994, 234.
1. H. Lund in Organic Electrochemistry: An 22. E. Kotani, N. Takeuchi, S. Tobinaga, J.
Introduction and a Guide (Eds.: H. Lund, Chem. Soc. Chem. Commun. 1973, 550.
M. M. Baizer), 3rd ed., Marcel Dekker, New 23. M. Sainsbury, J. Wyatt, J. Chem. Soc., Perkin
York, 1991, p. 701. Trans. I 1976, 661.
2. A. Sutterer, K. D. Moeller, J. Am. Chem. Soc. 24. J. M. Bobbitt, I. Noguchi, R. S. Ware et al.,
2000, 122, 5636. J. Org. Chem. 1975, 40, 2924.
3. K. D. Moeller, Tetrahedron 2000, 56, 9527. 25. J. Yoshida, T. Ishichi, S. Isoe, J. Am. Chem.
4. M. Huhtasaari, H. J. Schäfer, L. Becking, Soc. 1992, 114, 7594.
Angew. Chem., Int. Ed. Engl. 1984, 23, 980. 26. J. Yoshida, M. Sugawara, N. Kise, Tetrahe-
5. L. Becking, H. J. Schäfer, Tetrahedron Lett. dron Lett. 1996, 37, 3157.
1988, 29, 2797. 27. J. Yoshida, M. Sugawara, M. Tatsumi et al.,
6. T. Shono, H. Hamaguchi, Y. Matsumura, J. J. Org. Chem. 1998, 63, 5950.
Am. Chem. Soc. 1975, 97, 4264. 28. J. Yoshida, K. Takada, Y. Ishichi et al. in
7. R. Hazard, A. Tallec, Bull. Soc. Chim. Fr.
Novel Trends in Electroorganic Synthesis (Ed.:
1975, 679.
S. Torii), Kodansha, Tokyo, 1995, p. 295.
8. G. Cauquis, M. Genies, Tetrahedron Lett.
29. M. Sugawara, K. Mori, J. Yoshida, Elec-
1970, 3403.
trochim. Acta 1997, 42, 1995.
9. G. Cauquis, B. Chabaud, M. Genies, Bull.
30. N. L. Weinberg, E. A. Brown, J. Org. Chem.
Soc. Chim. Fr. 1973, 3487.
1966, 31, 4058.
10. J. D. Anderson, M. M. Baizer, J. P. Petro-
vich, J. Org. Chem. 1966, 31, 3890. 31. M. Okita, T. Wakamatsu, M. Mori et al.,
11. S. Donnelly, J. Grimshaw, J. Trocha-Grim- Heterocycles 1980, 14, 1089.
shaw, Electrochim. Acta 1996, 41, 489. 32. M. Okita, T. Wakamatsu, Y. Ban, Heterocy-
12. T. Shono, I. Nishiguchi, H. Ohmizu et al., cles 1983, 20, 401.
J. Am. Chem. Soc. 1978, 100, 545. 33. U. Slomczynska, D. K. Chalmers, F. Cor-
13. R. Hazard, A. Tallec, Bull. Soc. Chim. Fr. nille et al., J. Org. Chem. 1996, 61, 1198.
1973, 3040. 34. F. Cornille, Y. M. Fobian, U. Slomczynska
14. C. Degrand, D. Jacquin, Tetrahedron Lett. et al., Tetrahedron Lett. 1994, 35, 6989.
1978, 4955. 35. F. Cornille, U. Slomczynska, M. L. Smythe
15. C. Degrand, P. L. Compagnon, G. Belot et al., J. Am. Chem. Soc. 1995, 117, 909.
et al., J. Org. Chem. 1980, 45, 1189. 36. S. H. Pines, J. Org. Chem. 1973, 38, 3854.
16. M. Largeron, M. B. Fleury, J. Electroanal. 37. I. E. Marko, Tetrahedron Lett. 2000, 41, 4383.
Chem. 1988, 246, 373. 38. H. Noda, M. Niwa, S. Yamamura, Tetrahe-
17. E. Le Gall, J. P. Hurvois, T. Renaud et al., dron Lett. 1981, 22, 3247.
Liebigs Ann./Recueil 1997, 2089. 39. K. Irie, M. Okita, T. Wakamatsu et al., New
18. R. S. Glass, A. Petsom, G. S. Wilson et al., J. Chem. 1980, 4, 275.
J. Org. Chem. 1986, 51, 4337. 40. G. Popp, J. Org. Chem. 1972, 37, 3058.
41. I. Tabakovic, M. Lacan, S. Damoni, Elec- 67. K. Chiba, M. Fukuda, S. Kim et al., J. Org.
trochim. Acta 1976, 21, 621. Chem. 1999, 64, 7654.
42. I. Tabakovic, M. Trkovnik, D. G. Galijas, J. 68. G. Cauquis, M. Genies, Tetrahedron Lett.
Electroanal. Chem. 1978, 86, 241. 1971, 3959.
43. M. Lacan, V. Rogic, I. Tabakovic et al., Elec- 69. G. Cauquis, M. Genies, Tetrahedron Lett.
trochim. Acta 1983, 28, 199. 1971, 4677.
44. M. Tokuda, T. Miyamoto, H. Fujita et al., 70. G. Cauquis, B. Chabaud, C. R. Acad. Sci.
Tetrahedron 1991, 47, 747. Paris, Ser. C 1974, 279, 1061.
45. M. Tokuda, H. Fujita, T. Miyamoto et al., 71. M. Genies, Bull. Soc. Chim. Fr. 1975, 389.
Tetrahedron 1993, 49, 2413. 72. J. Lorans, J. P. Hurvois, C. Moinet, Acta
46. S. Karady, E. G. Corley, N. L. Abramson Chem. Scand. 1999, 53, 807.
et al., Tetrahedron 1991, 47, 757. 73. J. Lorans, F. Pierre, C. Moinet, Chem. Com-
47. R. Hazard, A. Tallec, Bull. Soc. Chim. Fr. mun. 1997, 1279.
1974, 121. 74. H. Baltes, L. Stork, H. J. Schäfer, Justus
48. C. Lamoureux, C. Moinet, Bull. Soc. Chim. Liebigs Ann. Chem. 1979, 318.
Fr. 1988, 59. 75. Z. Grujic, I. Tabakovic, M. Trkovik, Tetrahe-
49. C. Gault, C. Moinet, Tetrahedron 1989, 45, dron Lett. 1976, 4823.
3429. 76. I. Tabakovic, Z. Grujic, Z. Bejtovic, J. Hete-
50. A. Guilbaud, C. Moinet, Bull. Soc. Chim. Fr. rocycl. Chem. 1983, 20, 635.
1992, 295. 77. I. Tabakovic, S. Crljenak, Heterocycles 1981,
51. A. Guilbaud, C. Moinet, Bull. Soc. Chim. Fr. 16, 699.
1993, 101, 164. 78. D. Koch, H. J. Schäfer, Angew. Chem., Int.
52. B. A. Frontana-Uribe, C. Moinet, Tetrahe- Ed. Engl. 1973, 12, 245.
dron 1998, 54, 3197. 79. J. Y. Becker, E. Shakkour, J. A. R. P. Sarma,
53. B. A. Frontana-Uribe, C. Moinet, L. Toupet, J. Chem. Soc., Chem. Commun. 1990, 1016.
Eur. J. Org. Chem. 1999, 419. 80. J. Y. Becker, B. Zinger, S. Yatziv, J. Org.
54. B. A. Frontana-Uribe, C. Moinet, Acta Chem. 1987, 52, 2783.
Chem. Scand. 1999, 53, 814. 81. L. L. Miller, R. F. Stewart, J. L. Gillespie
55. A. Papadopoulos, B. Lewal, E. Steckan et al., et al., J. Org. Chem. 1978, 43, 1580.
Tetrahedron 1991, 47, 563. 82. M. M. Baizer, J. Electrochem. Soc. 1964, 111,
56. I. Tabakovic, M. Trkovnik, M. Batusic et al., 215.
Synthesis 1979, 590. 83. J. D. Anderson, M. M. Baizer, Tetrahedron
57. J. M. Bobbitt, C. L. Kulkarni, J. P. Willis, Lett. 1966, 511.
Heterocycles 1981, 15, 495. 84. T. Shono, N. Kise, E. Shirakawa et al., J.
58. R. Hazard, A. Tallec, Bull. Soc. Chim. Fr. Org. Chem. 1991, 56, 3063.
1976, 433. 85. R. Gorny, H. J. Schäfer, R. Fröhlich, Angew.
59. M. E. Niazymbetov, M. E. Ul’yanova, E. V. Chem., Int. Ed. Engl. 1995, 34, 2007.
Petrosyan, Izv. Akad. Nauk SSSR, Ser. Khim. 86. I. Carelli, A. Inesi, V. Carelli et al., Synthesis
1990, 3, 630. 1986, 591.
60. H. J. Schäfer, A. Al Azrak, Chem. Ber. 1972, 87. A. J. Fry, L. L. Chung, Tetrahedron Lett.
105, 2398. 1976, 645.
61. S. Torii, K. Uneyama, T. Onishi et al., 88. A. J. Fry, K. Ankner, V. Anda, Tetrahedron
Chem. Lett. 1980, 1603. Lett., 1981, 22, 1791.
62. J. Yoshida, K. Sakaguchi, S. Isoe, Tetrahe- 89. L. Walder in Organic Electrochemistry: An
dron Lett. 1986, 27, 6075. Introduction and a Guide, (Eds.: H. Lund,
63. J. Yoshida, S. Sakaguchi, S. Isoe et al., M. M. Baizer), 3rd ed., Marcel Dekker, New
Tetrahedron Lett. 1987, 28, 667. York, 1991, p. 809.
64. J. Yoshida, K. Sakaguchi, S. Isoe, J. Org. 90. J. Y. Nédélec, J. Périchon, M. Troupel, Top.
Chem. 1988, 53, 2525. Curr. Chem. 1997, 185, 141.
65. S. Wang, B. D. Gates, J. S. Swenton, J. Org. 91. S. Ozaki, H. Matsushita, H. Ohmori, J.
Chem. 1991, 56, 1979. Chem. Soc., Chem. Commun. 1992, 1120.
66. B. D. Gates, P. Dalidowicz, A. Teben et al., 92. S. Ozaki, H. Matsushita, H. Ohmori, J.
J. Org. Chem. 1992, 57, 2135. Chem. Soc. Perkin Trans. I 1993, 2339.
93. S. Olivero, J. C. Clinet, E. Dunach, Tetrahe- 119. H. Lund, S. Kwee, Acta Chem. Scand. 1968,
dron Lett. 1995, 36, 4429. 22, 2879.
94. S. Olivero, E. Dunach, J. Chem. Soc., Chem. 120. R. Hazard, A. Tallec, Bull. Soc. Chim. Fr.
Commun. 1995, 2497. 1971, 2917.
95. J. C. Clinet, E. Dunach, J. Organomet. Chem. 121. R. Bourgeois, A. Delay, R. Hazard et al.,
1995, 503, C48. Electrochim. Acta 1977, 22, 857.
96. M. Ihara, A. Katsumata, F. Setsu et al., J. 122. H. Lund, Acta Chem. Scand. 1967, 21, 2525.
Org. Chem. 1996, 61, 677. 123. E. Laviron, T. Lewandovska, Bull. Soc. Chim.
97. B. Giese, P. Erdmann, T. Göbel et al., Tetra- Fr. 1970, 3177.
hedron Lett. 1992, 33, 4545. 124. J. Yoshida, M. Yamamoto, N. Kawabata,
98. S. Torii, T. Inokuchi, T. Yukawa, J. Org. Tetrahedron Lett. 1985, 6217.
Chem. 1985, 50, 5875. 125. G. Montero, G. Quintanilla, F. Barba, Elec-
99. T. Inokuchi, H. Kawafuchi, S. Torii, J. Org. trochim. Acta 1997, 42, 2177.
Chem. 1991, 56, 5945. 126. T. Shono, H. Ohmizu, S. Kawakami et al.,
100. T. Inokuchi, H. Kawafuchi, K. Aoki et al., Tetrahedron Lett. 1980, 21, 5029.
Bull. Chem. Chem. Jpn. 1994, 67, 595. 127. T. Shono, Y. Usui, T. Mizukami et al.,
101. H. Tanaka, Q. Ren, S. Torii in Novel Trends Tetrahedron Lett. 1980, 21, 3073.
in Electroorganic Synthesis (Ed.: S. Torii), 128. T. Shono, M. Miyamoto, M. Mizukami et al.,
Kodansha, Tokyo, 1995, p. 195. Tetrahedron Lett. 1981, 22, 2385.
102. M. Le Guyader, C. R. Acad. Sci., Ser. C 1964, 129. F. Barba, M. D. Velasco, A. Guirado, Syn-
259, 4719. thesis 1981, 625.
103. M. Le Guyader, Bull. Soc. Chim. Fr. 1966, 130. F. Barba, M. D. Velasco, A. Guirado, Elec-
1867. trochim. Acta 1983, 593.
104. M. Cariou, R. Hazard, M. Jubault et al., J. 131. F. Barba, M. D. Velasco, A. Guirado, Syn-
Chem. Res. (S) 1986, 184. thesis 1984, 593.
105. S. Torii, H. Okumoto, M. A. Rashid et al., 132. F. Barba, M. D. Velasco, A. Guirado et al.,
Synlett 1992, 721. Synth. Commun. 1985, 15, 939.
106. H. Lund, L. G. Feoktitov, Acta Chem. Scand. 133. F. Barba, M. D. Velasco, A. Guirado et al.,
1969, 23, 3482. Electrochim. Acta 1985, 30, 1119.
107. A. Chibani, R. Hazard, M. Jubault et al., 134. J. Ludvik, F. Turecek, J. Volke, J. Elec-
Bull. Soc. Chim. Fr. 1987, 795. troanal. Chem. 1985, 188, 105.
108. R. Hazard, M. Jubault, C. Mouats et al., 135. P. Corbon, G. Barbey, A. Dupré et al., Bull.
Electrochim. Acta 1988, 33, 1335. Soc. Chim. Fr. 1974, 768.
109. C. Mouats, R. Hazard, E. Raoult et al., Bull. 136. F.Pragst, J. Prakt. Chem. 1979, 315, 549.
Soc. Chim. Fr. 1994, 131, 71. 137. F. Pragst, H. Köppel, W. Jugelt et al., J.
110. D. Sicker, H. Hartenstein, R. Hazard et al., Electroanal. Chem. 1957, 60, 323.
J. Heterocyclic Chem. 1994, 31, 809. 138. F. Pragst, C. Bock, J. Electroanal. Chem.
111. D. Sicker, H. Hartenstein, C. Mouats et al., 1975, 61, 47.
Electrochim. Acta 1995, 40, 1669. 139. P. Martigny, H. Lund, J. Simonet, Elec-
112. J. Hlavaty, Coll. Czech. Chem. Commun. trochim. Acta. 1976, 21, 345.
1985, 50, 33. 140. B. Kharraz, P. Uriac, L. Toupet et al., Tetra-
113. J. P. Hurvois, C. Moinet, A. Tallec, Elec- hedron 1995, 51, 9611.
trochim. Acta 1993, 38, 1775. 141. S. Torii, T. Okamoto, H. Tanaka, J. Org.
114. J. Y. David, J. P. Hurvois, A. Tallec et al., Chem. 1974, 39, 2486.
Tetrahedron 1995, 51, 3181. 142. T. Iwasaki, H. Horikawa, K. Matsumoto
115. E. Le Gall, T. Renaud, J. P. Hurvois et al., et al., Tetrahedron Lett. 1978, 4799.
Synlett 1998, 513. 143. H. Horikawa, T. Iwasaki, K. Matsumoto
116. M. Cariou, R. Hazard, M. Jubault et al., et al., J. Org. Chem. 1978, 43, 335.
Tetrahedron Lett. 1981, 22, 3961. 144. K. Matsumoto, H. Horikawa, T. Iwasaki
117. M. Cariou, R. Hazard, M. Jubault et al., et al., Chem. Ind. 1978, 920.
Can. J. Chem. 1983, 61, 2359. 145. A. Diaz, J. Org. Chem. 1977, 42, 3949.
118. M. Cariou, R. Hazard, M. Jubault et al., J. 146. J. M. Bobbitt, J. P. Willis, J. Org. Chem.
Electroanal. Chem. 1984, 182, 345. 1980, 45, 1978.
147. J. M. Bobbitt, T. Y. Cheng, J. Org. Chem. 174. Z. Blum, M. Malmberg, K. Nyberg, Acta
1976, 41, 443. Chem. Scand. 1981, B35, 739.
148. K. Yoshida, T. Fueno, J. Org. Chem. 1971, 175. L. Eberson, M. Malmberg, K. Nyberg, Acta
36, 1523. Chem. Scand. 1983, B37, 555.
149. J. Froborg, G. Magnusson, S. Thoren, J. 176. K. Warning, M. Mitzlaff, H. Jensen, Liebigs
Org. Chem. 1975, 40, 1595. Ann. Chem. 1978, 1707.
150. T. Shono, Y. Matsumura, Tetrahedron Lett. 177. K. Irie, M. Okita, T. Wakamatsu et al.,
1976, 1363. Nouv. J. Chim. 1980, 4, 275.
151. T. Shono, Y. Matsumura, H. Hamaguchi 178. K. Irie, Y. Ban, Heterocycles 1981, 15, 201.
et al., Chem. Lett. 1976, 1249. 179. K. Irie, Y. Ban, Heterocycles 1982, 18, 255.
152. T. Shono, H. Hamaguchi, K. Aoki, Chem. 180. M. Lennartz, M. Sadakane, E. Steckhan,
Lett. 1976, 1242. Tetrahedron 1999, 55, 14 407.
153. T. Shono, H. Hamaguchi, K. Aoki, Chem. 181. K. Danielmeier, K. Schierle, E. Steckan,
Lett. 1977, 1053. Tetrahedron 1996, 52, 9743.
154. T. Shono, Y. Matsumura, H. Hamaguchi, J. 182. M. A. Endoma, G. Butora, C. D. Claeboe
Chem. Soc., Chem. Commun. 1977, 712. et al., Tetrahedron Lett. 1997, 38, 8833.
155. T. Shono, Y. Matsumura, Y. Yamane et al., 183. J. Yoshida, S. Suga, S. Suzuki et al., J. Am.
Chem. Lett. 1980, 1619. Chem. Soc. 1999, 121, 9546.
156. T. Shono, Y. Matsumura, K. Tsubata et al., 184. T. Nishitani, H. Horikawa, T. Iwasaki et al.,
Chem. Lett. 1981, 1121. J. Org. Chem. 1982, 47, 1706.
157. H. Tanaka, Y. Kobayasi, S. Torii, J. Org. 185. P. G. M. Wuts, C. Sutherland, Tetrahedron
Chem. 1976, 41, 3482. Lett. 1982, 23, 3987.
158. S. Torii, H. Tanaka, T. Anoda et al., Chem. 186. P. Renaud, D. Seebach, Synthesis 1986, 424.
Lett. 1976, 495.
187. P. Renaud, D. Seebach, Helv. Chim. Acta.
159. D. G. New, Z. Tesfai, K. D. Moeller, J. Org.
1986, 69, 1704.
Chem. 1996, 61, 1578.
188. G. Kardassis, P. Brungs, E. Steckhan, Tetra-
160. J. Strogl, M. Janda, I. Stibor et al., Synthesis
hedron 1998, 54, 3471.
1975, 717.
189. K. Danielmeier, D. Kolter, M. Sadakane
161. K. Yoshida, J. Am. Chem. Soc. 1979, 101,
et al. in Novel Trends in Electroorganic Syn-
2116.
thesis (Ed.: S.Torii), Kodansha, Tokyo, 1998,
162. L. Eberson, Acta. Chem. Scand. 1980, B34,
747. p. 55.
163. T. Shono, Y. Matsumura, K. Tsubata, J. Am. 190. T. Shono, Y. Matsumura, S. Yamane, Tetra-
Chem. Soc. 1981, 103, 1172. hedron Lett. 1981, 22, 3269.
164. T. Shono, Y. Matsumura, K. Tsubata, Tetra- 191. S. Torii, T. Yamanaka, H. Tanaka, J. Org.
hedron Lett. 1983, 1259. Chem. 1978, 43, 2882.
165. T. Shono, Y. Matsumura, K. Tsubata, Org. 192. T. Shono, Y. Matsumura, O. Onomura et al.,
Synth. 1985, 63, 206. Chem. Lett. 1984, 1101.
166. N. C. Kaas, F. Limborg, K. Glens, Acta. 193. M. Mori, K. Kagechika, K. Tohjima et al.,
Chem. Scand. 1952, 6, 531. Tetrahedron Lett. 1988, 29, 1409.
167. N. C. Kaas, N. Elming, Z. Tyle, Acta. Chem. 194. M. Mori, K. Kagechika, H. Sasai et al.,
Scand. 1955, 9, 1. Tetrahedron 1991, 47, 531.
168. N. Elming, N. C. Kaas, Acta. Chem. Scand. 195. P. Renaud, S. Seebach, Angew. Chem., Int.
1955, 9, 23. Ed. Engl., 1986, 25, 843.
169. M. Libert, C. Caullet, Bull. Soc. Chim. Fr. 196. J. Froborg, G. Magnusson, S. Thoren, J.
1974, 805. Org. Chem. 1975, 40, 122.
170. A. J. Baggaley, R. Buttle, J. Chem. Soc. (C) 197. M. Libert, C. Caullet, Bull. Soc. Chim. Fr.
1966, 969. 1971, 1947.
171. P. D. Palasz, J. H. Utley, J. D. Hardstone, 198. M. Libert, C. Caullet, Bull. Soc. Chim. Fr.
Acta Chem. Scand. 1984, B38, 281. 1974, 800.
172. J. Y. L. Chung, J. T. Wasicak, W. A. Arnold 199. M. Libert, C. Caullet, M. S. Longchamp,
et al., J. Org. Chem. 1990, 55, 270. Bull. Soc. Chim. Fr. 1971, 2367.
173. K. Nyberg, R. Servin, Acta Chem. Scand. 200. B. Wermeckes, F. Beck, H. Schulz, Tetrahe-
1976, B30, 640. dron 1987, 43, 577.
201. B. Wermeckes, F. Beck, Chem. Ber. 1987, 228. J. R. Falk, L. L. Miller, F. R. Stermitz, Tetra-
120, 1679. hedron 1974, 30, 931.
202. M. Okita, T. Wakamatsu, Y. Ban, J. Chem. 229. L. L. Miller, F. R. Stermitz, J. Y. Becker
Soc. Chem. Commun. 1979, 749. et al., J. Am. Chem. Soc. 1975, 97, 2922.
203. T. Shono, Y. Matsumura, T. Kanazawa et al., 230. J. Y. Becker, L. L. Miller, F. R. Stermitz, J.
J. Chem. Res. (S) 1984, 320; (M) 1984, 2876. Electroanal. Chem. 1976, 68, 181.
204. T. Chiba, Y. Takata, J. Org. Chem. 1977, 42, 231. L. Christensen, L. L. Miller, J. Org. Chem.
2973. 1981, 46, 4876.
205. E. Le Gall, J. P. Hurvois, S. Sinbandhit, Eur. 232. E. Kotani, S. Tobinaga, Tetrahedron Lett.
J. Org. Chem. 1999, 2645. 1973, 4759.
206. E. Le Gall, R. Malassene, L. Toupet et al., 233. T. W. Bentley, S. J. Morris, J. Org. Chem.
Synlett 1999, 1383. 1986, 51, 5005.
207. T. Renaud, J. P. Hurvois, P. Uriac, Eur. J. 234. V. Palmquist, A. Nilsson, T. Petterson et al.,
Org. Chem. 2001, 987. J. Org. Chem. 1979, 44, 196.
208. S. Michel, E. Le Gall, J. P. Hurvois et al., 235. F. D. Saeva, B. P. Morgan, M. W. Fichtner
Liebigs Ann. Recueil. 1997, 259. et al., J. Org. Chem. 1984, 49, 390.
209. K. Yoshida, J. Am. Chem. Soc. 1977, 99, 236. G. Cauquis, A. Deronzier, J. L. Lepage et al.,
6111. Bull. Soc. Chim. Fr. 1977, 295.
210. S. Longchamp, C. Caullet, M. Libert, Bull. 237. A. F. Diaz in Organic Electrochemistry: An
Soc. Chim. Fr. 1974, 353. Introduction and a Guide, (Eds.: H. Lund,
211. Y. Hou, S. Higashiya, T. Fuchigami, J. Org. M. M. Baizer), 3rd ed., Marcel Dekker, New
Chem. 1997, 62, 8773. York, 1991, p. 1375.
212. A. Konno, W. Naito, T. Fuchigami, Tetrahe- 238. J. Roncalli, Chem. Rev. 1992, 92, 711.
dron Lett. 1992, 33, 7017.
239. D. Lelandais, C. Bacquet, J. Einhorn, J.
213. S. Narizuka, T. Fuchigami, J. Org. Chem.
Chem. Soc., Chem. Commun. 1978, 194.
1993, 58, 4200.
240. D. Lelandais, C. Bacquet, J. Einhorn, Tetra-
214. T. Fuchigami, M. Shimojo, A. Konno, J.
hedron 1981, 37, 3131.
Org. Chem. 1995, 60, 3459.
241. R. Kossaı̈, J. Simonet, G. Dauphin, Tetrahe-
215. H. Ishii, N. Yamada, T. Fuchigami, Tetrahe-
dron Lett. 1980, 21, 3575.
dron 2001, 57, 9062.
242. P. G. Gassman, I. Nishiguchi, H. Yama-
216. S. Higashiya, S. Narizuka, S. Konno et al.,
J. Org. Chem. 1999, 64, 133. moto, J. Am. Chem. Soc. 1975, 97, 1600.
217. T. Fuchigami, S. Narizuka, A. Konno et al., 243. Y. Kita, H. Maekawa, Y. Yamasaki et al.,
Electrochim. Acta 1998, 43, 1985. Tetrahedron Lett. 1999, 40, 8587.
218. T. Fuchigami, S. Narizuka, A. Konno, J. 244. L. Horner, H. Röder, Chem. Ber. 1968, 101,
Org. Chem. 1992, 57, 3755. 4179.
219. K. M. Dawood, T. Fushigami, Tetrahedron 245. J. Armand, K. Chekir, J. Pinson, Can. J.
Lett. 2001, 42, 2513. Chem. 1974, 52, 3971.
220. K. M. Dawood, T. Fushigami, J. Org. Chem. 246. J. Pinson, J. Armand, C. R. Acad. Sci. Paris,
2001, 66, 7691. Ser. C 1969, 268, 629.
221. K. M. Dawood, H. Ishii, T. Fuchigami, J. 247. J. Pinson, J. P. Launay, J.Armand, C. R.
Org. Chem. 2001, 66, 7030. Acad. Sci. Paris, Ser. C 1970, 270, 1881.
222. Y. Hou, S. Higashiya, T. Fuchigami, J. Org. 248. J. Armand, K. Chekir, J. Pinson et al., C. R.
Chem. 1999, 64, 3346. Acad. Sci. Paris, Ser. C 1975, 281, 547.
223. D. F. Andrès, V. Dietrich, E. G. Laurent 249. J. Armand, K. Chekir, J. Pinson, Can. J.
et al., Tetrahedron 1997, 53, 647. Chem. 1978, 56, 1804.
224. R. N. Renaud, P. J. Champagne, M. Savard, 250. J. Pinson, J. P. M’Packo, N. Vinot et al.,
Can. J. Chem. 1979, 57, 2627. Can. J. Chem. 1973, 50, 1581.
225. M. Yamanchi, S. Katayama, Y. Nakashita 251. D. L. Smith, P. J. Eling, J. Am. Chem. Soc.
et al., Synthesis 1981, 33. 1962, 84, 1412.
226. L. L. Miller, F. R. Stermitz, J. R. Falk, J. Am. 252. R. Hazard, A. Tallec, R. Tardivel et al., Elec-
Chem. Soc. 1971, 93, 5941. trochim. Acta 1990, 35, 1907.
227. L. L. Miller, F. R. Stermitz, J. R. Falk, J. Am. 253. E. Raoult, J. Sarrazin, A. Tallec, Bull. Soc.
Chem. Soc. 1973, 95, 2651. Chim. Fr. 1981, II, 420.
254. M. F. Nielsen, B. Batanero, T. Löhl et al., 267. C. Gosmini, J. Y. Nédélec, J. Périchon,

Chem. E. 1997, 3, 2011. Tetrahedron Lett. 2000, 41, 201.
255. M. Jubault, A. Tallec, B. Bujoli et al., Tetra- 268. E. Le Gall, C. Gosmini, J. Y. Nédélec et al.,
hedron Lett. 1985, 26, 745. Tetrahedron Lett. 2001, 42, 267.
256. B. Bujoli, M. Jubault, J. C. Rozé et al., Tetra- 269. R. Gottlieb, J. L. Neumeyer, J. Am. Chem.
hedron 1987, 43, 2709. Soc. 1976, 98, 7108.
257. B. Bujoli, M. Jubault, C. Moinet et al., Elec- 270. K. S. V. Santhanam, P. J. Elving, J. Am.
trochim. Acta 1990, 35, 805. Chem. Soc. 1973, 95, 5482.
258. P. Hudhomme, E. Raoult, A. Tallec et al., J. 271. J. Sarrazin, A. Tallec, J. Simonet, Elec-
Chem. Res. (S) 1995, 72. trochim. Acta 1982, 27, 1763.
259. A. Abouelfida, M. Jubault, J. P. Pradère 272. V. S. Griffiths, J. B. Westmore, J. Chem. Soc.
et al., Tetrahedron Lett. 1991, 32, 2225. 1962, 1704.
260. A. Abouelfida, J. P. Pradère, M. Jubault 273. R. N. Gourley, J. Grimshaw, P. G. Millar, J.
et al., Can. J. Chem. 1992, 70, 14. Chem. Soc. (C) 1970, 2318.
261. D. Rondeau, E. Raoult, A. Tallec et al., J. 274. F. Pragst, R. Ziebig, Electrochim. Acta 1978,
Chem. Soc., Perkin Trans. 2 1996, 2623. 23, 735; 1980, 25, 341.
262. F. Pragst, M. Janda, I. Stibor, Electrochim. 275. N. J. Leonard, S. Swann, J. Figueras, J. Am.
Acta 1980, 25, 779. Chem. Soc. 1952, 74, 4620.
263. T. Shono, S. Kashimura, Y. Yamaguchi 276. N. J. Leonard, S. Swann, E. H. Mottus, J.
et al., Tetrahedron Lett. 1987, 28, 4411. Am. Chem. Soc. 1952, 74, 6251.
264. H. Lund, J. Simonet, C. R. Acad. Sci. Paris, 277. G. T. Manh, R. Hazard, J. P. Pradère et al.,
Ser. C 1973, 277, 1387. Tetrahedron Lett. 2000, 41, 674.
265. C. Gosmini, S. Lasry, J. Y. Nédélec et al., 278. P. E. Iversen, J. O. Madsen, Tetrahedron
Tetrahedron 1998, 54, 1289. 1974, 30, 3477.
266. C. Gosmini, J. Y. Nédélec, J. Périchon, 279. B. A. Abd-El-Nabey, A. M. Kiwan, J. Elec-
Tetrahedron Lett. 2000, 41, 5039. troanal. Chem. 1979, 105, 365.
399
13
Selectivity in Electrochemical
Reactions
Toshio Fuchigami
Tokyo Institute of Technology, Yokohama, Japan
Tsutomu Nonaka
Tsuruoka National College of Technology, Tsuruoka, Japan
..
Hans J. Sch afer
..
Institute of Organic Chemistry, University of M unster, Germany
13.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
13.2 Regioselectivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 402

13.2.1 Regioselectivity at the Anode . . . . . . . . . . . . . . . . . . . . . . . . . . . 402
13.2.1.1 Regioselective Substitution of CH Bonds . . . . . . . . . . . . . . . . . . . 402
13.2.1.1.1 Regioselective Substitution of Unactivated CH Bonds . . . . . . . . . . 402
13.2.1.1.2 Regioselective Substitution of Activated CH Bonds . . . . . . . . . . . . 403
Benzylic CH bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403
Allylic CH bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404
CH bonds α to an amino group . . . . . . . . . . . . . . . . . . . . . . . . . 404
CH bonds α to an oxygen group . . . . . . . . . . . . . . . . . . . . . . . . . 407
CH bonds α to a sulfur or seleno group . . . . . . . . . . . . . . . . . . . . 407
Anodic substitution of aromatics . . . . . . . . . . . . . . . . . . . . . . . . 407
13.2.1.2 Regioselective Addition to Double Bonds . . . . . . . . . . . . . . . . . . . 408
13.2.1.3 Anodic Cleavage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408
13.2.1.4 Anodic C,C-Coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409
13.2.2 Regioselectivity in Cathode Reactions . . . . . . . . . . . . . . . . . . . . . 409
13.2.2.1 Regioselective Substitution . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409
13.2.2.2 Cathodic Addition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411
13.2.2.3 Cathodic Cleavage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 413
13.2.2.4 Cathodic Coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414
13.2.2.5 Electrogenerated Bases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
400 13 Selectivity in Electrochemical Reactions
13.3 Chemoselectivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415

13.3.1 General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
13.3.2 Chemoselectivity in Anode Reactions . . . . . . . . . . . . . . . . . . . . . 416
13.3.2.1 Anodic Dehydrogenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416
13.3.2.2 Anodic Cleavage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416
13.3.2.3 Anodic Substitution and Addition . . . . . . . . . . . . . . . . . . . . . . . . 418
13.3.3 Chemoselectivity in Cathode Reactions . . . . . . . . . . . . . . . . . . . . 419
13.3.3.1 Cathodic Hydrogenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419
13.3.3.2 Cathodic Cleavage and Elimination . . . . . . . . . . . . . . . . . . . . . . . 419
13.4 Stereoselectivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421

13.4.1 General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421
13.4.2 Diastereoselectivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 422
13.4.2.1 Diastereoselectivity at the Anode . . . . . . . . . . . . . . . . . . . . . . . . 422
13.4.2.1.1 Coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 422
13.4.2.1.2 Substitution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 424
13.4.2.1.3 Addition and Cycloaddition . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425
Addition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425
Cycloaddition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428
13.4.2.2 Diastereoselectivity at the Cathode . . . . . . . . . . . . . . . . . . . . . . . 428
13.4.2.2.1 Coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428
Activated olefins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428
Carbonyl compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
Intermolecular coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
Intramolecular coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433
Halides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434
13.4.2.3 Hydrogenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
C, C double and triple bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
C=X bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436
13.4.2.4 Cleavage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 438
13.4.2.5 Elimination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439
13.4.3 Enantioselectivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439
13.4.3.1 General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439
13.4.3.2 Anode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440
13.4.3.2.1 Coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440
13.4.3.2.2 Addition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440
13.4.3.2.3 Heteroatom Oxidation, De-hydrogenation . . . . . . . . . . . . . . . . . . 440
13.4.3.3 Cathode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440
13.4.3.3.1 Hydrogenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440
13.4.3.3.2 Cleavage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
401
13.1 part of reactions, while the major part

Introduction is irreversible and kinetically controlled.
In this case, the product distribution de-
In an electrochemical reaction, a com- pends on the activation energies of the
pound is converted by an electron transfer competing reactions. In electrochemical
at the electrode. This step is mostly fol- conversions, mostly reactive intermediates
lowed by a chemical reaction of the gener- such as radical ions, radicals, carbanions,
ated intermediate and possibly by further or carbocations are involved. Owing to
electron transfers (see Chap. 1). Selectivity their reactivity, the selectivity of the re-
tells us how the main product is formed actions can be lower as these are concerted
preferentially. The favored introduction of processes that constitute a large part of
a substituent into one out of several po- pure chemical reactions. However, the
sitions is termed as regioselectivity [1]. The nature of the electrode reaction provides
different reactivities of similar functional other means of controlling the selectiv-
groups toward a reagent are designated ity. While chemical reactions are mostly
as chemoselectivity. The preferred forma- homogeneous processes, electroorganic
tion of one out of several stereoisomers reactions are heterogeneous, involving an
is named stereoselectivity. The latter can electron transfer at the electrode surface
be further differentiated into diastereo- and mass transport to and from the elec-
selectivity, in which one out of several trode. This results in the formation of
diastereomers is formed selectively from a a reaction layer near the electrode sur-
prostereogenic center, and enantioselectiv- face, where the concentration of reactive
ity, in which one out of two enantiomers is intermediates is higher compared with
generated preferentially from a prostereo- homogeneous reactions. This allows to
genic center. influence reaction orders. As each elec-
The selectivity of reactions can be con- tron transfer results in the generation
trolled thermodynamically or kinetically. of protons at the anode and bases at
In the first case, the pathways leading the cathode, their concentration near the
from a starting material or a common in- electrode is often different from that in
termediate to the products are reversible. the bulk of the electrolyte. Additionally,
Here, the relative portion of the prod- substrates, intermediates, or products can
ucts is determined by their different heats be adsorbed at the electrode, which can
of formation. This constitutes the minor induce activation or deactivation, whose
extent is often controlled by the electrode incomplete. Therefore, the selectivities can
material and potential. The rate of sub- at best be correlated with the limited
strate conversion depends on the rate of set of available mechanistic data, and
electron transfer, which is related to the explanations must be adjusted when new
reduction or oxidation potential of the information arrives.
electrophore. This can be exploited for the
potential-selective conversion of substrates
as the oxidation or reduction power of the 13.2
working electrode can be more precisely Regioselectivity
adjusted and controlled via its potential
as is possible with the limited number A major part of regioselective conversions
of chemical reductants or oxidants. Elec- comprises additions to unsymmetrically
tronic and steric factors that influence substituted alkenes, substitutions in al-
activation energies can be enhanced or lylic positions or in aromatic compounds,
diminished by the large potential gradient conversions of anions, radicals, or carboca-
at the electrode and the bulkiness of the tions with two reactive sites, and reactions
electrode that can shield parts of the react- at different CH bonds.
ing molecule. Furthermore, the electrode
can be used to regenerate selective chem- 13.2.1
ical oxidants or reductants that can then Regioselectivity at the Anode
be used catalytically in indirect electrolyses
(see Chap. 15). 13.2.1.1 Regioselective Substitution
Selectivity in homogeneous reactions is of CH Bonds
treated in Refs. [2–6], while the selectivi-
ties that are influenced in heterogeneous 13.2.1.1.1 Regioselective Substitution of
reactions by diffusion and adsorption are Unactivated CH Bonds CH bonds in cy-
dealt with in Refs. [7, 8]. Kinetics and cloalkanes (decaline, steroids) and alkanes
mechanisms of electrochemical reactions bearing electron-deficient groups in re-
are covered in Chap. 1 of this volume and mote positions (1,2-dichlorocyclohexane,
in Refs. [9–11]. decanoic acid) can be regioselectively sub-
In electroorganic conversions, the stituted at the anode by trifluoroacetate,
knowledge of the mechanism is mostly acetate, or methoxide (Figs. 1, 2) [12–14].
R1
R1
CH2Cl2/MeOH,
−e, C, 77−80%
(Based on conversion)
OR2
R1: H, C 8H17
R2: OCH 3,
OCH2OCH3
Fig. 1 Regioselective C6-methoxylation and methoxymethoxylation of

steroids [12].
13.2 Regioselectivity 403
Cl CF3CO2 Cl
CH2Cl2, CF3CO2H
−e, 49%
Cl Cl
Fig. 2 Regioselective trifluoroacetoxylation of
1,2-dichlorocyclohexane [13, 14].
The reaction occurs by oxidation of the 13.2.1.1.2 Regioselective Substitution of

CH bond to a radical cation that is de- Activated CH Bonds
protonated to a radical. This is further
oxidized to a carbocation that reacts with Benzylic CH bonds Benzylic CH bonds
the nucleophiles in the electrolyte. The can be preferentially substituted at the
regiochemistry is controlled by inductive anode by oxidation of the aromatic ring to
deactivation (−I-substituents) as well as by a radical cation, which can undergo side-
activation (+I-substituents), which leads to chain substitution at the benzylic carbon
a reactivity: tert.H > sec.H > prim.H. In atom and/or nuclear substitution. Benzylic
steroids, a preferential adsorption appears substitution preponderates, when there
to play a role. is an alkyl substituent at the aromatic
With ketones, a remote regioselec- carbon bearing the highest positive charge
tive acetamidation is found. This result density in the radical cation, while a
is mechanistically in accordance with hydrogen at this position leads to a
the oxidation of the oxygen atom of nuclear substitution [16]. Anodic benzylic
the carbonyl group to a radical cation substitution is used in technical processes
that abstracts a hydrogen from a re- for the conversion of alkyl aromatics
mote CH bond. The generated radical into substituted benzaldehydes [17, 18].
is then oxidized to a cation, that re- Anodic benzylic substitution has been
acts with acetonitrile to get the acetamide used for the regioselective methoxylation
(Fig. 3) [15]. of estratrienone at C9 (Fig. 4) [19].
O O
CH3CN
−e
NHCOCH3 21%
+ 6-isomer (30%)
+ 5-isomer (7%)
Fig. 3 Remote acetamidation of ketones [15].
O O
CH3
CH3OH/CH2Cl2
O
> 90%
MeO CH3O
a:b = 3:2
Fig. 4 Regioselective methoxylation of 3-methoxy-estratrienone at C9 [19].

Anodic oxidation of p-methylbenzyl- (citronellol) is converted, possibly by in-

sulfonic ester, -carboxylic ester, and tramolecular assistance, to 26% (3) [25]
-nitrile in Et3 N·3HF/CH3 CN affords flu- or 56% (4) [26] in the key step of a
orides and acetamides at the methyl rose oxide synthesis. Regioselective elec-
(Me) and substituted (CH2 E) benzyl po- trochemical chlorination of the methyl
sition: Me/CH2 E = 24/76 (E = CO2 Et), group in the 3-methyl-3-butenoate moi-
9/91(CN), 69/31 (SO3 Et). In the radical ety of penicillin derivatives was found
bromination of these compounds, substi- in dichloromethane : water : sodium chlo-
tution at CH3 is enhanced [20]. ride:sulfuric acid as electrolyte [27]. The
reaction possibly involves a chloro-ene
reaction.
Allylic CH bonds Aliphatic alkenes fre-
quently undergo allylic substitution by
CH bonds α to an amino group Anodic
oxidation of the double bond to a radi-
methoxylation of unsymmetrical tertiary
cal cation that undergoes deprotonation amines takes place preferentially at the
at the allylic position and subsequent ox- methyl group (Fig. 6) [28–30]. Substitu-
idation of the resulting allyl radical to a tion at a CH bond α to an amino group
cation, which finally combines with the proceeds by oxidation of the amino group
nucleophiles from the electrolyte [21, 22]. to a radical cation, followed by deprotona-
The selectivity is mostly low. Regioselec- tion at the adjacent CH bond to a radical.
tive allylic substitution or dehydrogenation This is oxidized to a cation, which under-
is, however, found in some cases with goes solvolysis, in this case, methanolysis.
activated alkenes, for example, ß-ionone The regioselectivity has been explained by
that reacts to (1) (Fig. 5) as a major prod- assuming that an adsorbed amine from
uct [23], menthone enolacetate that yields which the intermediate cation is formed
90% (2) [24], and 3,7-dimethyl-6-octen-1-ol is as distant as possible from the anode
O
O
O OCH3 OH
OAc
(1) (2) (3) (4)
Fig. 5 Examples of regioselective allylic substitution [23–26].
Me Me
−2e−, −H+ OMe
Y N Y N + Y N
MeOH
R R R
OMe
Y = Me, R = Ph 70 : 30
Y = MeOCO, R = Me 65 : 35
Y = Ph, R = Me 80 : 20
Fig. 6 Anodic methoxylation of tertiary amines and carbamates [28–30].

MeO
(less easily) (more easily) +
CH3 CH2
−H+, −e
+• CH3 CH2N
CH2 N CH3
Anode
Fig. 7 Proposed explanation for the regioselectivity in
methoxylation of N-benzyl-N, N-dimethylamine [28].
(Fig. 7) [28]. However, other explanations terms of the different deprotonation rates
for this unexpected regioselectivity have of the radical cation intermediate.
also been proposed [31, 32]. Anodic methoxylation of 2,3-dimethyl-
The oxidation of N -benzyldiethanola- 1-phenyl-5-pyrazolone (antipyrine) occurs
mine afforded 45% 3-benzyl-oxazolidine regioselectively at the N -methyl group,
as the major product. This was attributed leading to a selective demethylation [34].
to the fragmentation of the intermedi- Anodic methoxylation of unsymmetrical
ate radical cation, a 1e oxidation of the carbamates affords a mixture of regioiso-
radical, and the intramolecular combina- mers (Fig. 6) [29]. However, the regiose-
tion of the cation with the hydroxyl group lectivity can be completely controlled by
(Fig. 8) [28]. an electroauxiliary [35]. This is achieved
A different regioselectivity has been by prior introduction of a trimethylsilyl or
reported in the anodic methoxylation phenylthio group at one of the α-carbon
of N -(fluoroethyl) anilines as shown in atoms; selectivity arises because the silyl
Fig. 9 [33]. Since in this case, the regio- cation or thiyl radical are better leaving
selectivity decreases with the decreasing groups than the proton (Fig. 10) [36, 37].
electron-withdrawing ability of the Rf Direct anodic methoxylation of biscarba-
groups (−I-effect), it can be explained in mates of a methyl α, ω-diaminocarboxylate
CH2CH2OH
+• −H+, −CH2 O
C6H5 CH2 N C6H5CH2 N O
−e, −H+
CH2 CH2O H
45%
Fig. 83-Benzyl-oxazolidine formation from N-benzyldiethanolamine by
fragmentation and intramolecular alkoxylation [28].
OMe (29%) OMe (72%) OMe (80%)
H3C CH3 CH3 CH3
PhN CF3 PhN CF3 PhN CHF2 PhN CH3
OMe (85%) OMe (71%) OMe (28%) OMe (20%)
Fig. 9 Regioselectivity in anodic methoxylation of N-(fluoroethyl)anilines [33].

Z OMe
−e−, −Me3Si+ or −PhS•
MeOCON MeOCON
Ph MeOH Ph
(Z = Me3Si, PhS) Selectivity 100%
Fig. 10 Regioselective anodic methoxylation of
unsymmetrical carbamates using electroauxiliaries [36, 37].
takes place predominantly at the ω- imposed by the slowly rotating N -

position, while indirect anodic methoxy- acyl group [43]. Similar results were
lation occurs selectively at the α-position found in the cyanation of 2-alkyl-N -
(Fig. 11) [38–40]. In indirect chloride- phenylpiperidines, in which the major
mediated methoxylation, methyl hypochlo- isomer has a trans configuration with
rite is formed as the reactive intermediate an axial cyano group and an equato-
that generates the N -chloro compound. rial alkyl substituent. 4-Methyl-6-pentyl-
HCl elimination forms the intermediate N -phenyl piperidine afforded the trisub-
N -acylimino acid ester that adds methanol. stituted ax-6-cyano compound as a sin-
The chloride-mediated anodic methoxyla- gle diastereomer [44]. Anodic cyanation of
tion of protected dipeptide esters shows N -ethyl-N -methylaniline proceeds with a
a high regioselectivity. It is influenced by regioselectivity similar to that of anodic
the N -protecting groups and the amino methoxylation [45]. With cyclic N -alkyl
acid side chains and can be directed amines, the cyano group is preferentially
towards the selective oxidation of the C- introduced into the 5- or 6-membered ring
terminal amino acid [41]. Regioselective α to the nitrogen atom. This selectivity in-
oxidation of the N -terminal amino acid is creases with increasing bulkiness of the
achieved by the direct electrolysis of N -(2- N -alkyl group [46].
nitrophenylsulfenyl)-protected dipeptides A silyl group α to the nitrogen atom
with the intermediate formation of the in tetrahydroisoquinolines and piperidines
sulfenimino dipeptide [42]. governs the regiochemistry, leads to an
Anodic methoxylation of conformation- exclusive cyanation at this position, and
ally biased 2-substituted N -acyl piperidines additionally lowers the oxidation potential
leads regioselectively to 6-methoxy prod- compared to the nonsilylated analogs [47].
ucts owing to the steric constraints Anodic cyanation of N -2,2,2-trifluoroethyl
OMe
CO2Me
−2e (Direct) HN (CH2)n
Et4NOTs / MeOH
CO2Me CO2Me NHCO2Me
HN (CH2)n
CO2Me NHCO2Me MeO

−2e (Indirect) CO2Me
HN (CH2)n
NaCl / MeOH
(n = 1,2) CO2Me NHCO2Me
Fig. 11 Regioselective methoxylation of N, N-biscarbamates of methyl

α, ω-diaminocarboxylates [38–40].
amines occurs with fair yield and selectivity selenides have been achieved [61–63]. The
at the positions α to nitrogen that are not monofluorination of heterocycles also pro-
adjacent to the CF3 group [48]. ceeds regioselectively (Eq. 1) [64–66].
R S −2e, F− R S F
CH bonds α to an oxygen group The
oxygen atom of an alkoxy group directs X X
substitution to the α-carbon atom, be- O O
cause oxygen is oxidized to a radical cation (X = S, O, NR′)
that leads, as in the case of amines, to (1)
the generation of a carbocation in the α- Partial fluorination of 4-arylthio-1,3-
position. Tetrahydrofuran (THF) and other dioxolan-2-ones occurs preferentially at
ethers have been hydroxylated and alkoxy- the carbon atom adjacent to the thio
lated at the α-carbon atom in medium group [67]. However, a remarkable sol-
to good yields [49–52]. Cyclic ethers, lac- vent effect is encountered. In the more
tones, and a cyclic carbonate are regioselec- polar solvent, dimethoxyethane substi-
tively monofluorinated in Et3 N·5HF [53]. tution occurs, while in the less po-
For the methoxylation of unsymmetrical lar dichloromethane a larger portion of
ethers, the indirect oxidation with tris(2,4- the desulfurization with cleavage of the
dibromophenyl)amine as mediator proved phenylthio group takes place. This is at-
to be favorable. With this procedure, sec- tributed to the fact that the intermediate
ondary carbon atoms in the presence of radical cation is more stable in the po-
primary and tertiary ones α to the oxygen lar solvent and undergoes deprotonation,
atom can be selectively methoxylated [54]. while in the less polar solvent, the less
The oxidation of hydroxy groups to oxo stabilized radical cation dissociates into a
groups in cholic acid proceeds at dif- dioxolane cation and a phenylthio radical.
ferent rates, namely, at C7 > C12 >
C3 [55]. In polyhydroxylated triterpenes, Anodic substitution of aromatics Anodic
the 3-OH group has been regioselectively nuclear methoxylation of arenes occurs
oxidized by indirect oxidation with KI as predominantly at the carbon bearing
the mediator [56]. the highest positive charge density in
the intermediate radical cation. If this
CH bonds α to a sulfur or seleno group position is occupied by a poor leaving
Anodic methoxylation and acetoxylation of group, for example, an alkyl group,
alkyl and phenyl sulfides and selenides, a side-chain substitution occurs [16],
bearing at the α-carbon atom beside hydro- with better leaving groups an ipso-
gen and an electron-withdrawing group, substitution is found. Regioselective side-
such as CN or CF3 , proceed highly regio- chain substitution of alkylarenes is
selectively at this site to afford α-methoxy a method that is also of technical
or acetoxy products [57–60]. The regiose- importance for their conversion to
lectivity is controlled by the deprotonation acetals of benzaldehydes [17, 18, 68,
rate of the sulfur or selenium radical 69]. Methoxycycloheptatrienes undergo
cations as in the case of the fluoroalkyl- a regioselective methoxylation at the
amines. Also, highly regioselective anodic carbon atom bearing the methoxy
mono- and difluorination of sulfides and group, finally leading to substituted
tropones [70, 71]. Presumably by way via an intermediate selenium cation

of an ECE (electrochemical, chemical, that undergoes methanolysis at the
electrochemical)-process, a tropylium higher alkylated carbon atom (Fig. 12) [79].
cation is formed, which undergoes For further regioselective oxy-, hydroxy-,
methanolysis at the methoxylated carbon and acetamido-selenations of olefins, see
atom. Anodic cyanation of dibenzofuran Ref. [80].
in MeOH/NaCN leads via an intermediate Anodic regioselective acetamidosulfeny-
radical cation predominantly to the 3- lation of alkenes is similarly achieved
isomer, while in electrophilic cyanation by oxidation of diphenyldisulfide in ace-
with BrCN/AlCl3 the 2-isomer is tonitrile [81]. Cyclic enamines, which are
obtained regioselectively [72]. Anodic intermediates in the oxidation of cyclic N -
cyanation of 1,4-dimethoxybenzene and methoxycarbonyl amines, react in aqueous
1,2,3-trimethoxybenzene affords in an acetonitrile that contains chloride ions to
ipso-substitution 4-methoxy- and 2,6- α-hydroxy-β-chloro compounds via inter-
dimethoxybenzonitrile, respectively [45]. mediate chloronium ions [82]. Enolethers
Pyrrole and indol undergo a highly undergo a regioselective azidomethoxyla-
regioselective anodic cyanation to provide tion to yield acetals of α-azido carbonyl
2-cyano products [73]. Anodic oxidation compounds upon electrolysis in methanol
of dialkyldisulfides in SO2 and in the containing sodium azide [83]. The reac-
presence of arenes, such as anthracene, tion proceeds possibly via addition of an
phenol, and xylene, yields alkyl aryl anodically generated azide radical.
sulfides predominantly in the p-position of Lithium (E)- or (Z)-δ-alkenylamides are
the electron-donating substituent in good converted regio- and stereoselectively in
to excellent yield [74]. Anodic oxidation of a 5-exo-trig-cyclization of an intermedi-
terminal alkynes in NaI/MeOH affords 1- ate amide radical to substituted pyrro-
iodoalkynes exclusively [75]. lidines [84].
13.2.1.2 Regioselective Addition to Double 13.2.1.3 Anodic Cleavage

Bonds By analogy with their behavior in
Substituted 1,4-dimethoxybenzenes [76], mass spectrometry, branched hydrocar-
furan [77], and dienes [78] undergo exclu- bons are cleaved upon oxidation in
sively to predominantly 1,4-dialkoxylation acetonitrile/TEABF4 to afford acetamides
upon electrolysis in alcohol or an in- of fragments that originate from an
ert solvent with alcohol added. The intermediate radical cation by cleavage
reaction proceeds via an intermediate between the secondary and tertiary car-
radical cation that undergoes solvol- bon atoms [85]. Anodic cleavage of cy-
ysis at the positions of the high- clopropanes can proceed quite regioselec-
est positive charge density. Anodic se- tively depending on the reaction condi-
lenoalkoxylation proceeds regioselectively tions and the kind of substituents (Fig. 13)
−2e, 90%
Br−/(PhSe)2/MeOH
MeO OH
OH
SePh
Fig. 12 Regioselective anodic selenoalkoxylation [79].

Cl
MeOH-Lutidine-NaClO4-(C) Cl
21–86% n = 4, 5, 6 ( )n CO2Me
R = Et
Cl
( )n Cl
OR
MeOH-LiClO4-Fe(NO3)3-(Pt)
CO2Me
H
39–97% ( )n
n = 4, 5, 10; R = SiMe3 O
Fig. 13 Anodic cleavage of cyclopropanes [86, 87].
1. −2e, AcOH, 4 F mol−1

HO
2. OH −
H
77%
Fig. 14 Anodic cleavage of a tricyclene [88].
[86, 87]. A tricyclene has been converted 13.2.2

in acetic acid/Et3 N to Nojigiku alcohol Regioselectivity in Cathode Reactions
with a 77% yield by regioselective cleavage
at the external cyclopropane C−C bond 13.2.2.1 Regioselective Substitution
(Fig. 14) [88]. Cathodic substitution stands for C,C
bond or C, heteroatom bond formation
with cathodically generated anions. The
13.2.1.4 Anodic C,C-Coupling
question of regioselectivity is encountered
Anodic C, C-coupling is a very power- in the reaction of such anions with allyl
ful tool to synthesize cyclic compounds halides (path a) or in the reaction of allyl
with high regio- and stereoselectivity. It in- anions generated in an ECE process from
volves inter- and intramolecular coupling allyl halides (path b). Cathodic reductive
of arylolefins, dienes, enolethers, phenol silylation of an allyl halide proceeds
ethers, and aromatic amines and often regioselectively at the less substituted
opens a quick entry into complex nat- position (Fig. 15) [91]. From the reduction
ural products in a few steps. Although potentials of the halides it is proposed that
the mechanism is fully established in the reaction follows path b.
only a few cases, it does appear to in- Regioselectivity in the cathodic allyla-
volve the coupling of two radical cations tion of ketones and aldehydes is greatly
at the site of their highest radical den- affected by the relative ease of the reduc-
sity and is further controlled by steric tion of the allyl halide compared with that
constraints. This important type of re- of the carbonyl compound. When the car-
action is reviewed in Chap. 5 and in bonyl compound is more easily reduced
Refs. [89, 90]. than the allyl halide, the allylation takes
R1 +e, TEATos R1
+ ClSiMe2R3
DMF
R2 Cl R2 SiMe2R3
25–98%
R = Ph, R2 = H, R3 = Me
1
R1 = Me, R2 = Cl, R3 = Ph
Fig. 15 Regioselective cathodic silylation of allyl chlorides [91].
place preferentially at the less substituted aluminum afforded chiefly allylation at the
carbon atom to give homoallyl alcohols, more substituted allylic carbon, while with
which are not so easily obtained by chem- carbon or mercury, allylation took place at
ical methods. When, however, the allyl both termini of the allyl group.
halide is more easily reduced than the car- The cathodic coupling of prenyl chlo-
bonyl compound, the allylation happens ride with diethyl fumarate and methyl
preferentially at the more highly substi- crotonate proceeds with different regios-
tuted carbon atom of the allyl group, which electivities as shown in Fig. 17 [94]. Also
would be the addition of a cathodically in this case, the change in the regioselec-
generated allyl anion at the carbonyl group tivity appears to be due to the reduction
(see Sect. 13.2.2.2, Fig. 16, and [92, 93]). of the diethyl fumarate to a radical anion
In this case, the regioselectivity is addi- that undergoes a nucleophilic substitution
tionally greatly influenced by the cathode at the prenyl chloride, and in the other
material, where platinum, zinc, nickel, and case there is a 2e reduction of the prenyl
R1 X R1 O 2e, H+
R2
or 40–80%
+ R3
R2 R4
X
E1red E2red
R3 R1 R2
R1 R3
R4 +
OH R4
R2 OH
E1red < E2red : minor major
E1red > E2red : major minor
Fig. 16 Regioselective cathodic addition of allyl substituted allyl halides

to carbonyl compounds [93].
2e, H+ CO2Et
CO2Me 2e, H+
Cl
EtO2C
CO2Me CO2Et CO2Et

22% 15%
Fig. 17 Regioselective cathodic addition of prenyl chloride to α, β-unsaturated esters [94].

chloride to an allyl anion with a subsequent to 1,4-cyclohexadienes [98] belongs to the

Michael addition. first type, in which the proton from
Vitamin B12 -catalyzed intramolecular an appropriate donor acts as the elec-
cathodic coupling leads to a regioselective trophile. Possibly, Li+ from the sup-
1,4-addition with formation of a spirocom- porting electrolyte operates as a media-
pound (Eq. 2) [95]. This chain reaction is tor [99]. Cathodic reduction of substituted
initiated by the reduction of Co(III) to a 1-methoxy-cycloheptatrienes in the pres-
Co(I) species, which reacts in an oxidative ence of isopropylchloride was found to
addition with the alkyl bromide. The result- be an effective method for regioselec-
ing alkyl-Co(III)-Br species is then reduced tively introducing the isopropyl group
to an alkyl anion that undergoes a Michael at C6 of the seven-membered ring sys-
addition and yields Co(I) for the next cycle. tem [100]. An example of the cathodic
addition of allyl halides to aliphatic aldehy-
O O
des and ketones has already been given in
2e, H+ Sect. 13.2.2.1. Correspondingly, homoal-
Vitamin B12 lylic alcohols were synthesized in the cou-
(CH2)4Br
pling of aromatic aldehydes and ketones
(2) with allylic acetates catalyzed by iron(I)
An interesting case of a cathodic sub- complexes generated from FeBr2 and a sac-
stitution is the EuCl3 -mediated reduction rificial Fe anode. The regioselectivity with
of oxygen that reacts with aliphatic CH unsymmetrical allyl groups was in favor
bonds. The selectivity of 1-H : 2-H : 3-H of the branched product in a ratio of 96 : 4
being 1 : 6 : 19 was attributed to a radi- to 100 : 0 versus the linear product [101].
cal intermediate, while in the aromatic With the activated zinc obtained by the
substitution the preferred ortho- and para- cathodic reduction of ZnBr2 , an unusual
substitution points to an electrophilic oxy- regioselectivity was found in the reac-
gen species [96]. In the FeCl3 -mediated tion of the trifluorinated analogs of prenyl
oxygenation of n-hexane in a fuel cell, bromide with carbonyl compounds [102].
the addition of α- and β-cyclodextrins im- When the aldehyde was sterically hin-
proved the selectivity toward oxygenation dered α-alkylation occurred and with an
of the terminal CH3 -groups due to inclu- unhindered aldehyde γ -allylation was ob-
sion of the n-hexane in the cyclodextrin served. γ -Allylation is always found with
cavity [97]. prenyl bromide. In the nickel-catalyzed in-
tramolecular transfer of allyl moieties from
13.2.2.2 Cathodic Addition substituted allyl ethers to a carbonyl group
Cathodic addition involves either the re- a regioselectivity toward the branched
duction of a π-system in an ECEC process isomer was found [103]. Electrolysis of
(electrochemical, chemical, electrochemi- 3-mono and 3,3-disubstituted allylic bro-
cal, chemical) and the chemical reaction mides in the presence of carbon dioxide
(C) of the intermediates with a carbon (1 atm) at a Pt cathode and a Mg anode gave
or heteroatom electrophile or the ca- regioselectively the corresponding 4-mono
thodic conversion of a C−X bond in an and 4,4-disubstituted 3-alkenoic acids with
ECE process into an anion that adds a 34 to 71% yield [104]. Reduction of
to an electrophilic π-system. The elec- vinyl phosphonates at a Mg cathode in
trochemical Birch reduction of arenes the presence of acid anhydrides brought
about the regioselective C-acylation to Ni(bipy)3 (BF4 )2 is a regioselective process,

the corresponding ß-acyl phosphonates. in which carboxylation takes place mainly
The reaction may proceed via the radi- at the 2-position of terminal alkynes [108].
cal anion of the vinyl phosphonate that The regioselective carboxylation of non-
undergoes acylation [105]. Electrolysis of conjugated diynes has also been re-
unsubstituted or α-substituted propargylic ported [109]. In the electrocarboxylation of
bromides in the presence of aldehydes several allenes with nickel(II) complexes
gave exclusively homopropargylic alcohols and a sacrificial Mg anode, unsaturated
in high yields, while with γ -substituted carboxylic acids are obtained. The regio-
propargylic bromides the homoallenyl al- selectivity of the carbon dioxide incorpora-
cohols were obtained as major products tion in the central or terminal position of
(Fig. 18) [106]. Regioselectivity was con- the allene depends on steric and electronic
trolled via the material of the sacrificial effects [110]. Cathodic intramolecular cou-
anode (zinc, aluminum). This was ex- pling of nonconjugated enones proceeds
plained with the preferred formation of both in a regioselective 5-exo-trig cycliza-
γ -substituted propargyl-α-zinc bromides tion and with high diastereoselectivity
and γ , γ -disubstituted allenyl-α-zinc bro- (Fig. 20) [111].
mides, which reacted with the aldehyde in Also, intermolecular coupling with di-
a six-membered transition state. enes has been satisfactorily accomplished
The nickel-catalyzed electrochemical using a carbon fiber cathode. In the
carboxylation of 1-(perfluoroalkyl) alkenes case of unsymmetrically substituted di-
proceeds regioselectively to afford 4- enes, a high regioselectivity toward the
fluoro-4-perfluoroalkyl-3-alkenoic acids via less substituted terminal double bond was
a Ni(II)-allyl complex and a final F− elimi- found [112]. Electroreduction of noncon-
nation (Fig. 19) [107]. Electrochemical car- jugated enones and ynones containing
boxylation of alkynes in the presence of a sulfur or a nitrogen atom in the
− + HO HO
Pt Zn
Ph CH O + + •
0.1 M TEAP Ph Ph
Br DMF
90% 100 : 0
Br − + HO HO
Pt Zn
PhCH O + + •
0.1 M TEAP Ph Ph
DMF
93% 25 : 75
Fig. 18 Regioselective cathodic addition of propargyl bromides to
aldehydes [106].
(1) e, Ni(II)
RfCF2CH CHR + CO2 RfCF CH CHR
(2) K2CO3, MeI
CO2Me
Fig. 19Cathodic carboxylation of perfluoroalkyl olefins with
subsequent fluoride elimination [107].
Fig. 20 Regio- and Me

e HO
stereoselective cathodic 3 Me
intramolecular coupling of Dioxan, MeOH
O TEATOS
nonconjugated enones [111].
66%
Br HO HO
O 4e , 3H
H H
+
1 M H2SO4 H
N N N H
73% 13.0:1
Fig. 21 Regio- and stereoselective cathodic cyclization of a 4-oxoalkyl
pyridinium salt [114, 115].
connecting chain brought about regio- Thereby, either a localized or delocalized

and stereoselective cyclization to afford radical anion is formed in the first
heteroatom containing cyclic alcohols in step that undergoes cleavage to a radical
moderate to good yields [113]. Regioselec- and X− . The radical is further reduced
tive intramolecular coupling is also found to an anion that is finally protonated.
in the cathodic reduction of oxoalkyl pyri- Tetrachloropicolinate is regioselectively
dinium salts to yield polycyclic pyrrolidines dechlorinated at the 4- and 5-position,
and piperidines (Fig. 21) [114, 115]. The re- which is attributed to the controlled
action proceeds presumably via reduction orientation of the substrate at the electrode
of the hydrogen-bonded carbonyl group surface owing to the dipole moment of the
to a nucleophilic hydroxyalkyl radical that molecule (Eq. 3) [117].
undergoes addition to the electrophilic
C=N double bond of the pyridine. With Cl Cl
3-substituted pyridines, a preferential or- Cl CO2− CO2−
4e−, +2H+
thocoupling against a paracoupling occurs N −2Cl− N
Cl
(see also Sect. 13.4.2).
Cl Cl
Cathodic reduction of N -(2-iodophenyl)-
Cathode Dipole moment
N -alkylcinnamides under deaerated condi-
(3)
tions forms 1-alkyl-3-benzylindolin-2-ones
Pentachloropyridine undergoes a regio-
regioselectively (70–85%), presumably in
selective dechlorination to give 2,3,5,6-
a radical or anionic 5-exo-trig process. The
tetrachloropyridine [118]. The reduction of
mechanism has been explored by the use
1- and 2-phenoxynaphthalene at the cath-
of cyclic voltammetry, controlled-potential
ode or by an alkali metal afforded phenol
electrolysis (cpe), and deuterium label- and naphthalene. The intermediacy of
ing [116]. the naphthalene radical has been made
probable by the use of an internal radi-
13.2.2.3 Cathodic Cleavage cal trap [119]. 5-Aryloxy-1-phenyltetrazoles
In cathodic cleavage, a C−X bond is cleave reductively predominantly at the
reductively converted to a C−H bond. tetrazolyl-O bond. The relative rates of
differently substituted aryloxy rings are bond cleavage takes place selectively
roughly related to the pKa values of (Eq. 4) [124].
the corresponding phenols [120]. The re- The allylic sulfonyl group is regioselec-
gioselective cleavage of a hydroxyl group tively cleaved in the presence of the alkyl-
is possible in hydroxymethyl pyridines sulfonyl group by indirect reduction with
since the electron-withdrawing pyridine anthracene as a mediator (Fig. 24) [125].
ring selectively activates the 4-position
DMF,
(Fig. 22) [121]. (CH2)nSO2−
( )n−1 Et4NCIO4
Reductive ring opening of cyclic N -alkyl +e
anilinium salts happens regioselectively at S
O O n: 2–4
the N -aryl bond to form an N, N -dialkyl
> 50%
amine. A 2e reduction has been proposed,
followed by cleavage to the most stable (4)
carbanion (Fig. 23) [122].
Acyclic alkyl phenyl sulfones undergo 13.2.2.4 Cathodic Coupling
an alkyl-sulfur bond cleavage [123]; how- Cathodic coupling involves C, C bond
ever, in cyclic arylsulfones the aryl-sulfur formation by reduction of an activated
OH Me
2e, 2H+ HO
HO OH
OH −H2O
Me N Me N
Fig. 22 Regioselective cleavage of a hydroxyl group [121].
(CH2)n−1 (CH2)n NR2

2e, H+
N
R R Fig. 23 Reductive cleavage of
(n = 2–4) 88–90% cyclic anilinium salts [122].
Me 2e, H+ Me
PhO2S SO2Ph Anthracene mediator SO2Ph
Me
Fig. 24 Regioselective cleavage of allyl sulfones [125].
Me Me
O 2e−, +H+ O Fig. 25 Cathodic
Me Me
intramolecular
hydrodimerization of a
O O bis-enone [128].
13.3 Chemoselectivity 415
C=C or a C=X double bond. Thereby, BuI, C6 H5 CH2 Br, 38–84%) [131, 132].
in most cases radical anions or radicals,
O O
the latter produced in an EC process, cou- −+ Me
Me (1) Ph3CNEt4
ple. Activated olefins such as acrylonitrile
R
and alkyl acrylates undergo regioselective (2) RX
ß,ß-coupling to form the corresponding (5)
hydrodimers [126]. On the other hand, As an entry into O-functionalized di-
cathodic coupling of α, β-unsaturated car- saccharides, the cathodic deprotonation of
bonyl compounds yields mixtures of 1,1 -, hydroxy groups and the subsequent trap-
1,3 - and 3,3 - regioisomers depending on ping of the alkoxide with suitable reagents
electronic and steric factors. With vinyl were evaluated. The regioselectivity was
alkyl ketones all three isomers are formed, correlated by way of computer simulations
while with styryl alkyl ketones exclusively to electrostatic potential profiles of the rel-
the 3,3 -isomer is obtained [127]. The in- evant conformers of sucrose [133].
tramolecular coupling of enones proceeds
highly regioselectively owing to steric con-
straints (Fig. 25) [128]. 13.3
Cathodic reduction of retinal leads to a Chemoselectivity
regioselective coupling in the presence of
malonic ester to produce the correspond- 13.3.1
General
ing pinacol (Fig. 26) [129]. Chromium(III)
ions facilitate the reduction and favor
Chemoselectivity describes the preferred
the regioselective coupling of conjugated
formation of one out of several products
dienones to pinacols. A Cr(III)-carbonyl
due to the selective interaction of a reagent
compound complex is evidenced as the
with the substrate. In electroorganic con-
reason for the selectivity [130].
version, the electrode is the reagent that
can influence the reaction course in several
13.2.2.5 Electrogenerated Bases ways: The electrode material can form im-
Electrogenerated bases (see Chap. 14) can mobilized organometallics or oxides that
be prepared in situ and tailored for regiose- can shift the conversion like mediators
lective deprotonation. Regioselective alky- from an outer sphere electron transfer to a
lation of an unsymmetrical cyclic ketone more selective inner sphere electron trans-
was achieved by using an electrogenerated fer [134]. Overvoltages can suppress the
triphenylmethyl anion (Eq. 5, RX = CH3 I, hydrogen evolution in cathodic reduction
2e
O CH2(COOEt)2
50%
OH
)
2
Fig. 26 Cathodic hydrodimerization of retinal [129].

at mercury or graphite in protic elec- be accurately set by electronically adjusting

trolytes [135] or the anodic oxygen genera- the potential of the working electrode and
tion at graphite. By appropriate treatment holding it constant throughout the whole
the electrode surface can be made more hy- electrolysis (cpe). This allows the potential-
drophilic [136] or more hydrophobic [137]. selective conversion of one out of several
The roughness of the electrode surface in- electrophores.
fluences the concentration of the reactive
intermediates formed by electron trans- 13.3.2
fer. A large real electrode surface inherent Chemoselectivity in Anode Reactions
to the material, e.g. pyrolytic graphite,
promotes first-order reactions owing to a 13.3.2.1 Anodic Dehydrogenation
lower concentration of reactive interme- Partially protected carbohydrates can be
diates, while a smooth surface, e.g. plat- selectively oxidized at the primary hydroxy
inum, favors second-order conversions, group to uronic acids at the nickel hydrox-
for example, in the Kolbe reaction [138]. ide electrode. At the same electrode, in
Likewise, the current density can favor polyhydroxy steroids, a preferential oxida-
first-order (low current density) or second- tion of the sterically better accessible hy-
order conversions of the electrogenerated droxyl groups is achieved [142]. By way of
intermediate (high current density). The the mediator, TEMPO, carbohydrates that
kind of supporting electrolyte can cre- are only protected at the anomeric hydroxyl
ate a hydrophilic electrode surface, for group are selectively oxidized at the pri-
example, hydrated Li+ favors hydrogena- mary hydroxyl group (Fig. 27) [143–145].
tion in the cathodic reduction of activated Anodic oxidation of a mixture of cis-
olefins, while the tetrabutylammonium cyclohexane-1,2-diol and cyclohexanol in
cation can make the electrode surface more methanol containing dibutyltin oxide and
hydrophobic than the bulk electrolyte, thus Et4 NBr provides 2-hydroxycyclohexanone
promoting hydrodimerization in the re- selectively, while cyclohexanol is recov-
duction of activated olefins [139]. Redox ered almost completely (Fig. 28) [146]. The
catalysts (mediators) (see Chap. 15 and cyclic intermediate dibutyl-(1,2-dioxycyclo-
Ref. [140]) can change the reaction course hexyl)stannan is oxidized indirectly by Br+ .
by decreasing overvoltages that may occur The chemoselectivity can be strongly
in direct electron transfer and by pro- changed by the anode material. The oxida-
ceeding via more selective inner sphere tion of glycolaldehyde at a platinum anode
transfer routes. affords mainly glyoxal while the conver-
The substrate can change the reactiv- sion with a platinum anode modified by
ity in the interaction with the reagent antimony or bismuth ad-atoms provides
by means of its electrophilicity, nucleo- mainly glycolic acid (Fig. 29) [147].
philicity, and hardness [4, 141]. These
properties can be accentuated by elec- 13.3.2.2 Anodic Cleavage
troauxiliaries [35] that facilitate electron Potential-selective cleavage is a powerful
transfer and direct follow-up reactions. A method for potential-selective deprotec-
powerful control is the potential of the elec- tion. Benzyl ethers can be cleaved to
trophore that is determined by electronic benzaldehyde and alcohol via oxidation
factors, steric accessibility, and intramole- of the benzyl group to a radical cation
cular electron transfer. This potential can (Fig. 30) [148]. With the radical cation of
OH
O
HO
HO OH N
+
OH O
O R O•
HO
OH
H3COOC
O H3COOC
1. −e HO O
2. (CH 3O)2C(CH3)2 HO O
HO R
HCl OH
OH
R Yield [%]
OCH3 69
N3 63
Fig. 27 Chemoselective oxidation of primary OH-groups in carbohydrates with

TEMPO as mediator [143–145].
OH OH O OH
−2e, −2H+
+ +
Bu2Sn O (0.1 equiv)
OH Et4NBr OH
in MeOH 87% 99%
O O
SnBu2 SnBu2Br
O O
Br+ Br−
2e
Fig. 28 Chemoselective oxidation of 1,2-cyclohexandiol in the presence of

cyclohexanol [146].
−2e −2e
HO COOH HO CHO OHC CHO
Sb-Pt anode Pt anode
Bi-Pt anode
Fig. 29 Chemoselective oxidation of gycolaldehyde [147].
OH
−e
CH2 O R CH O R CHO + ROH
−H+, H2O
Yield: 74−98% R: Octyl, cholesteryl, bornyl
Fig. 30 Anodic deprotection of benzyl ethers [148].

tris(p-bromophenyl)amine in the presence of the allylsilane moiety is selectively

of 2,6-lutidine the cleavage occurs under oxidized owing to the electron-donating
even milder conditions than can be used effect of the ß-silyl group (Fig. 32) [153].
for a mediated process [149]. By variation Unsaturated α-heteroatom organosili-
of the oxidation potential of the radical con, organotin, and organosulfur com-
cation owing to a different substitution pounds undergo selective cleavage of the
of the trisarylamine, a selective deprotec- C−Si, C−Sn, and C−S bond respectively,
tion of diols protected with a benzyl and with the subsequent intramolecular addi-
a p-methoxybenzylgroup becomes possi- tion of the generated carbocation to the
ble [150, 151]. double bond (Fig. 33) [154, 155].
Chemoselective anodic methoxylation at
a distinct carbon atom in the α-position
13.3.2.3 Anodic Substitution and Addition to an amino group in a polypeptide
Chemoselective oxidation of 3-arylsul- was achieved by prior introduction of
fenylmethyl-3 -cephem affords 3-meth- a silyl group as an electroauxiliary at
oxymethyl-3 -cephem in an anodic sub- this carbon atom [156]. Amide oxidation
stitution. From the two thioethers, the in N -acetylpyrrolidines substituted with
arylthio group is more easily oxididized electron-rich phenyl rings led to either
to a radical cation, that then undergoes methoxylation α to the nitrogen atom
cleavage to a thiyl radical and a carbocation or in the benzylic position. Mechanistic
(Fig. 31) [152]. studies indicate that both the amide
In the case of anodic oxidation of ger- and the phenyl oxidation compete, but
anyltrimethylsilane, the C=C double bond intramolecular electron transfer leads to
R1CONH S R1CONH S
−e, −ArS •
N SAr MeOH N OMe
O O
CO2R2 CO2R2
Fig. 31 Chemoselective anodic substitution of an arylthio group [152].
−2e +
SiMe3 −Me3Si+
Fig. 32 Chemoselective cleavage of the allylsilane moiety [153].
Y
+
O −e O F− O
C7H15 C7H15 C7H15 F
(Y = Me3Si, Bu3Sn, MeS)
Fig. 33 Selective cleavage of C−Si, C−Sn, and C−S bonds [154, 155].
the selective formation of an amide electrohydrogenation of the nitroaromatic

oxidation product [157]. and nitroaliphatic functional groups in
molecules that contain other groups that
13.3.3 are easy to hydrogenate (e.g., activated
Chemoselectivity in Cathode Reactions double bond, carbon–iodine bond, nitrile)
was carried out in slightly acidic (pH 3) or
13.3.3.1 Cathodic Hydrogenation near neutral MeOH-H2 O solutions at De-
Electrocatalytic hydrogenation has the ad- varda Cu and Raney Co electrodes [161].
vantage of milder reaction conditions Electrochemical and chemical reduction
compared to catalytic hydrogenation. The of multifunctional molecules can proceed
development of various electrode materials with different chemoselectivities. While
(e.g., massive electrodes, powder cath- in nitroketones the carbonyl group is
odes, polymer film electrodes) and the selectively reduced with NaBH4 [162], in
optimization of reaction conditions have nitroesters the nitro group is preferentially
led to highly selective electrocatalytic hy- reduced at the cathode [163].
drogenations. These are very suitable for
the conversion of aliphatic and aromatic 13.3.3.2 Cathodic Cleavage and
nitro compounds to amines and α, β- Elimination
unsaturated ketones to saturated ketones. In polyfunctional molecules, the elec-
The field is reviewed with 173 references trophore with the least negative reduction
in [158]. While the reduction of conju- potential is selectively cleaved [164]. A
gated enones does not always proceed bromine atom at a carbon atom α to a
chemoselectively at a Hg cathode, the carbonyl group is fairly easily reducible;
use of a carbon felt electrode coated with therefore, cpe at the potential in which
polyviologen/Pd particles provided satu- this C−Br bond is reduced proceeds highly
rated ketones exclusively (Fig. 34) [159]. chemoselectively (Fig. 35) [164].
Solvents exert control on the chemose- Potential selective cathodic bond cleav-
lective hydrogenation of alkenes bearing age is of considerable importance for de-
a benzyloxy protecting group [160]. In protection [165–174]. As shown in Fig. 36,
the unpolar solvent benzene, only the the C−X bond can be easily cleaved with
double bond is hydrogenated, while in a high selectivity, when an unsaturated
methanol, acetone, and ethyl acetate, the group Y is attached in the α-position to
benzyloxy group is also removed. Selective the carbon.
Fig. 34 Chemoselective 2e, +2H+

R O R O
electrocatalytic hydrogenation Pd-impregnated
of conjugated enones [159]. cathode
O O
Cl Cl
2e, +H+
Br 94%
Br Br
Fig. 35 Chemoselective cathodic cleavage in polyfunctional
molecules [164].
Some further examples of selective Carboxylic acids can be protected as 2-

deprotection in the presence of other haloethyl derivatives. These are reducible
reducible functional groups are shown in at different potentials depending on the
Figs. 37–40. kind and the number of halogen sub-
In the tetrabromide of 4-vinyl-1-cyclo- stituents at C2 (Fig. 40) [178]. This kind
hexene, the higher alkylated double of protecting group has been employed in
bond could be selectively deprotected by a nucleotide synthesis using the triester
cpe [177]. method [179].
R R
e e −
X− +
X Y X Y−• R Y
X,Y: SR, C 6H5CO; CH 2CO2Et, SO2C6H5; OR, pyridyl; SBT, CO2 Me;
O2CC6H5, CN; OAc, C=C-CO 2R; OR, 10-oxo-9-anthracenyl.
Fig. 36 Chemoselective cathodic deprotection [165–173].
Z Z
Ar Ar e, H+ Ar
S S S SH
O O O
Fig. 37 Chemoselective
(Z = C, N) cathodic deprotection [174].
OCOMe e
71%
Fig. 38 Selective cathodic deprotection [175].
O O
CH3
OCOR 2e
H+
O O
Fig. 39 Selective cathodic deprotection [176].
2e
PhCOOCH2CCl3 PhCOOCH2CCl2− PhCO2 + CH2 CCl2
−Cl−
87%
Fig. 40 Potential-selective deprotection of esters [178].

13.4 Stereoselectivity 421
13.4 from variations in transition state ener-

Stereoselectivity gies due to spatially directed steric and
electronic interactions between the re-
13.4.1
actants. In organic electrochemistry, the
General
mechanism and control of the stereochem-
ical course has not been studied in such
In coupling, substitution, or addition
width and depth as in organic chemistry.
reactions, stereogenic centers are trans-
However, in these cases of electrochem-
formed into other ones or generated
istry, in which the factors influencing
from prostereogenic groups. This creates
the stereochemistry have been studied in
stereoisomers that have the same con- some detail, the same controls have been
stitution, but different configurations. A found as in homogeneous chemical reac-
molecule with n stereogenic centers can tions. There are, however, some additional
form 2n stereoisomers (diastereomers and effects inherent to the electrochemical
enantiomers). Stereoselectivity means that reaction that are frequently found in mech-
one out of several possible stereoisomers anistic discussions. They arise from the
is preferentially formed. Diastereoselec- heterogeneous nature of the electrochem-
tivity designates the preferred formation ical process and the vicinity of the reaction
of one diastereomer; enantioselectivity of layer to the electrode surface, which creates
one major enantiomer. Stereochemistry in conditions that are different from these in
organic reactions and the stereoselective homogeneous reactions. Furthermore, the
construction of new stereogenic centers intermediate may be absorbed by nonco-
is one of the central and very lively top- valent forces or bound covalently to the
ics in organic chemistry today, as was electrode. The substrate may be converted
demonstrated by the Nobel prize of 2001 in an inner sphere electron transfer by
dedicated to this field. Control of stereo- immobilized metal oxides in anode pro-
selectivity means to channel a reaction cesses or transition metal complexes in
predominantly to one stereoisomer, which cathodic conversions. These factors, how-
increases its yield and avoids the often ever, have to be identified in the individual
very difficult separation of stereoisomers. case by comparing the stereoselectivity of
The topics of stereochemistry, stereose- the same conversion by chemical and elec-
lectivity, and stereoselective synthesis are trochemical means, which has not as yet
covered, for example, in Refs. [180–182]. been rigorously done. In the meantime,
Diastereoselective synthesis with chiral the advanced knowledge about factors that
auxiliaries [183] and catalytic enantiose- increase the diastereo- and enantioselec-
lective syntheses [184, 185] are efficiently tivity in homogeneous reactions has to
and increasingly used to prepare complex be used to improve the stereoselectivity
molecules in high enantiomeric purity. in electrochemical conversions. To exploit
These are applied, for example, in research the controls that are in principle offered
in the life sciences and in the synthesis of by the electrochemical reaction layer and
pharmaceuticals and agrochemicals. adsorption, the knowledge about these
Stereoselectivity arises from small dif- phenomena has to be extended by fun-
ferences in the activation energies of damental research on this topic applied
competing reactions leading to different to organic molecules and their reactions.
stereoisomers. These differences originate In the meantime, the usual approach to
complex systems, namely, optimization via case of trans-4-phenylcyclohexanecarboxy-

systematic variation of the reaction condi- lates and of cis-4-phenyl-2-cyclohexene-
tions has to be applied. carboxylates, the distribution of stereoiso-
meric dimers indicates that adsorption
13.4.2 might slightly influence the product dis-
Diastereoselectivity tribution.
Carboxylates with different nonracemic
Diastereoselectivity denotes the prefer- chiral auxiliaries have been anodically de-
ential formation of one out of several carboxylated to explore the face-selective
diastereoisomers. Selected examples are heterocoupling of the intermediate rad-
presented in the following text for anodic icals. With (2R, 5R)-2,5-dimethylpyrroli-
and cathodic C, C bond formations and for dine as the chiral amido group and an
functional group interconversions. increasing size of the substituents R1
and R2 selectivities up to 86% de (di-
astereomeric excess) have been obtained
13.4.2.1 Diastereoselectivity at the Anode (Fig. 41) [189, 190]. The results point to
an increasing portion of an intermediate
13.4.2.1.1 Coupling Anodic decarboxy- radical with Z-conformation and a grow-
lation of carboxylic acids (Kolbe elec- ing steric hindrance for the si-approach.
trolysis) generates alkyl radicals that With oxazolidine, 2,10-camphersultame,
can couple, disproportionate, or be fur- and menthol auxiliaries, the diastereo-
ther oxidized [138]. The first route leads selectivity is lower. Heterocoupling of 2-
to homo- and heterocoupling products, carboxy-butyrolactones with a stereogenic
which are treated in this section, the center in the α-position to the intermediate
last route generates substitution prod- radical leads to 2-substituted butyrolac-
ucts (see Sect. 13.4.2.1.2). Enantioen- tones with a 33 to 43% yield and up to
riched 2-alkyl substituted alkyl mal- 88% de (Fig. 42) [191].
onates yield racemic heterocoupling prod- The results show that, in the coup-
ucts [186, 187]. The same holds for ling of anodically generated radicals,
the homocoupling of trans- and cis-4-t- good diastereoselectivities can only be
butylcyclohexanecarboxylates [188]. In the achieved when the intermediate radical
O O O
N OH −e, −CO2 N •
•
+ R2CO2H + R2
R1 R1
O O
R2 R2
N N
+
R1 R1
R1 = CH2C6H5, C(CH3)3, C(CH3)2Et R2 = C4H9, CH2C(CH3)3, C(CH3)2Et

16−69% yield, 20−86% de
Fig. 41 Diastereoselective coupling of radicals in the Kolbe
electrolysis [189, 190].
R1 CO2H R1 R3 R1 R3
R2 R3CO2H R2 R2
O O + O
R2 O −H+, −e−, −CO2 R2 O R2 O
trans major cis minor
R1 = Ph, i-Pr, t-Bu R2 = Me, H R3 = CH3, C(CH3)2 CO2Et

33−43% yield, 0−88% de
Fig. 42 Diastereoselective coupling of radicals in the Kolbe
electrolysis [191].
adopts a preferred conformation and the which the diastereoselective formation of

substituents efficiently shield one face of atropo-isomers has been observed only in
the radical. These observations correspond a few cases. There the TEMPO/sparteine-
to those found in homogeneous radical re- mediated enantioselective homocoupling
actions [192]. Stereogenic centers at the of 2-naphthol has been described (see
ß-carbon atom of the acid and more re- Sect. 4.3.2.1). Furthermore, the oxida-
mote positions retain their configuration tive coupling of 1,2-dimethyl-7-hydroxy-6-
as expected. The same holds for double methoxy-1,2,3,4-tetrahydrolisoquinoline at
bonds except for the (Z)-4-enoic acids that a graphite felt anode yielded an 8,8 -
partially isomerize to (E)-products via a re- coupling product that had the R, R and
versible ring closure to cyclopropylcarbinyl S, S but not the R, S configuration at
radicals [193]. C1 [196]. An aspidosperma class alkaloid
The anion of methyl phenylacetate, has been regio- and diastereoselectively de-
formed by an electrogenerated base, was hydrodimerized by the anodic coupling of
homocoupled with iodine or anodically an aryl with an enaminoester moiety [197].
mediated by iodide to afford dimethyl The intramolecular coupling of eno-
2,3-diphenylsuccinate in high yield and lethers with enolethers, styrenes, dienes,
high d, l-selectivity. This reaction prob- alkyl-substituted olefins, allylsilanes, and
ably does not involve free radicals but vinylsilanes was systematically studied by
an iodination-nucleophilic substitution se- Moeller [90, 198–200]. These couplings al-
quence [194, 195]. low the smooth formation of quaternary
Oxidation of arylolefins, enolethers, or carbon atoms in fused bicyclic rings having
dienes yields intermolecular homocou- a cis stereochemistry (Fig. 43) [201, 202].
pling products in moderate to good Ketene dithioacetal enolethers under-
yield (see Sect. 13.2.1.4); however, no went stereoselective intramolecular cou-
pronounced diastereoselectivity was ob- pling to yield trans- or cis-disubstituted
served. This is also due to the fact five- or six-membered cycloalkanes in
that the coupling sites do not toler- high stereoselectivity and yield [203]. In
ate substituents that would make up a the intramolecular coupling of an allyl-
prostereogenic center. Furthermore, the silane, a five-membered ring with three
fairly stable cations of the dimerized rad- contiguous stereogenic centers was stereo-
ical cation solvolyze stereounselectively. selectively formed without loss of a very
The same holds for the intermolecu- acid sensitive allylic, alkoxy group [204].
lar coupling of aromatic compounds, in The intramolecular coupling of a furan
MeO
OTBDMS
MeO
a, 75%
MeO
O TMS
TBDMS H
a : C-anode, 1 M LiClO 4, MeOH/THF, lutidine

Fig. 43 Stereoselective intramolecular coupling of enolether with
allylsilane [201, 202].
TBS O O
H
C, −e TsOH, rt
LiClO4
MeOH,
TBS OO CH2Cl2 HO O
2,6-lutidine
88%
Fig. 44 Stereoselective cyclization of a silyl enolether and a
furan [205].
ring with a silylenolether was used to diastereoselectively fluorinated in the α-

stereoselectively assemble the tricyclic core position by anodic oxidation with Et3 N,
ring system of alliacol A (Fig. 44) [205]. 3HF/MeCN as electrolyte. The observed
The electrolysis proceeded in high yield diastereoselectivities are discussed in con-
and could be accomplished with the use of nection with the chiral auxiliary and the
a 6-V lantern battery. role of the anode [208].
For further examples of the stere-
oselective synthesis of ring systems,
see anodically initiated cycloadditions in
Sect. 13.4.2.1.3.
CH3O CH2 CO2
13.4.2.1.2 Substitution Anodic substitu-
tion designates the oxidative replacement (5)
of a hydrogen atom, a silyl, or a carboxyl
group (non-Kolbe electrolysis) by a nucleo- RO
philic carbon or heteroatom.
Anodic oxidation of 2-t-butylindan in N
acetic acid led predominantly to side-chain
CO2Me
acetoxylation at a Pt or PbO2 anode. The
cis/trans ratio of the two acetates is signi- (6)
ficantly higher in the anodic process than
in the related homogeneous reactions, in- Anodic α-methoxylation of (3-R)-1-
dicating that adsorption at least partially methoxycarbonylpyrrolidinol derivatives
controls the anodic reaction [206, 207]. (6) (R = H, Ac, SiMe2 t-butyl) displays
Menthyl 4-methoxyarylacetate (5) could be a modest stereoselectivity. However,
substitution of the anodically introduced that is further oxidized to a carbocation,

methoxy group with a cyano group leads which reacts with nucleophiles present
with R = TBDMSi to a stereoselectivity in the electrolyte (non-Kolbe electroly-
of up to 86% de [209]. Anodic sis) [215]. Decarboxylation of exo- and endo-
methoxylation of conformationally biased bicycloalkane carboxylic acid, depending
4-t-butylpiperidine-1-carboxaldehyde gave on the electrolyte, leads to methoxy-
axial 2-substitution owing to the steric lation, hydroxylation, or acetamidation
constraints imposed by the N -acyl in low diastereoselectivity [216, 217]. Cy-
group [210]. In anodic cyanation of N - clopropyl carboxylic acids, besides rad-
alkyl-substituted tetrahydroquinolines and ical coupling, undergo a ring cleavage
N -phenylpiperidines, the cyano group was to allyl methyl ethers, whose stereo-
selectively introduced at C2 in the axial chemistry points to a concerted elec-
position [211]. Chiral electrophilic glycine trocyclic ring opening of a cyclopropyl
equivalents (7) and (8) were generated cation [218, 219]. Electrochemical decar-
by anodic methoxylation of heterocycles boxylation of L-threonine and oligopeptide
that incorporated L-proline and L-leucine derivatives forms N -acyl-N ,O-acetals with
as chiral auxiliaries [212]. a moderate diastereoselectivity. These can
be further converted by reaction with
organometallics or trialkylphoshites and
H H the resulting diastereomers can be sepa-
O Me2CH N O
N rated by HPLC (high performance liquid
NH chromatography) [220]. Trans-4-hydroxy-L-
O O N OMe
H proline was converted by anodic de-
OMe
carboxylation and TiCl4 mediated reac-
(7) (8)
tion with nucleophiles to enantiomerically
pure pyrrolidines [221] or (3R)-3-hydroxy-
4-aminobutyric acid (GABOB) [222]. A
S
very interesting retention of configuration
F
SOO
2
(91.5%) is found in the anodic decar-
O boxylative methoxylation of serine deriva-
Me2N
tives (Fig. 45) [223]. The restricted rotation
(9) of the bulky o-phenylbenzoyl protecting
group preserves the stereochemical infor-
ß-Hydroxypiperidine alkaloids have mation in the intermediate iminium cation
been synthesized via anodic methoxylation and leads by facial shielding to a high de-
that allowed the regio- and stereoselective gree of retention in the cation-methanol
introduction of substituents [213]. A recombination.
highly diastereoselective fluorination was
achieved with chiral 1,3-oxathiolan-5-ones 13.4.2.1.3 Addition and Cycloaddition
derived from camphorsulfonamide. In
dimethoxyethane containing Et4 NF·4HF, Addition In anodic addition, either the
the monofluorinated product (9) was olefin is oxidized to a radical cation that
obtained as a single diastereomer [214]. reacts with the nucleophilic species in the
Anodic substitution of a carboxylic acid electrolyte or the nucleophile is oxidized
involves decarboxylation to an alkyl radical to a radical that adds to the double bond.
O O
Me Me
−2e 2F mol−1
N COOH N OMe
Me Pt cathode Me
O NaOMe (10 equiv.) O

in MeOH
Ph Ph
Anode ee
Graphite 72%
Pt 83%
Fig. 45 Stereoselective methoxylation of serine derivatives by
anodic decarboxylation [223].
The route that is taken depends on the side product, while the major prod-
oxidation potential of the nucleophile and ucts arise from allylic substitution and
the olefin. rearrangement [225, 230]. Furans react
Acetoxylation proceeds mostly via the in a 1,4-addition to 2,5-dimethoxy-2,5-
radical cation of the olefin. Aliphatic dihydrofurans, in which the trans di-
alkenes, however, undergo allylic substi- astereomer predominates [231]. Anodic
tution and rearrangement predominantly methoxylation of benzothiophenes pro-
rather than addition [224, 225]. Aryl- ceeds with a low diastereoselectivity of
substituted alkenes react by addition to cis:trans = 4 : 3 indicating some shield-
vic-disubstituted acetates, in which the dia- ing effect of the anode [232]. A larger
stereoselectivity of the product formation shielding effect in the anodic addi-
indicates a cyclic acetoxonium ion as inter- tion of methanol to (E, E)-1,4-diphenyl-
mediate [226, 227]. In acenaphthenes, the 1,3-butadiene with a syn:anti ratio of
cis portion of the diacetoxy product is sig- 8.9 : 1 has been observed for the 1,4-
nificantly larger in the anodic process than adduct [233]. The aromatic compound
in the chemical ones indicating that some pseudocumene affords in a 1,4-addition
steric shielding through the electrode is with a 30% yield trans-3,6-dimethoxy-1,3,6-
involved [228]. trimethylcyclohexa-1,4-diene as the major
The stereoselective intramolecular cou-
product [234]. The stereoselectivity of the
pling of a ketene dithioacetal to an oxygen
fluoroacetamidation of a variety of olefins
nucleophile to afford (10), was used as
has been rationalized as due to the adsorp-
a key step in the total synthesis of (+)-
tion of the olefin, fluoride anion, and the
nemorensic acid [229].
resulting oxidized olefinic species on the
anode surface (Fig. 46) [235–237].
Me Chloroacetamidation of unsaturated car-
Me Me bohydrates occurs with substrate depen-
S
O dent stereoselectivity [238]. For iodoac-
MeO S
etamidation of cyclohexene [239], a trans
(10)
selectivity has been reported. Nitroac-
etamidation of the conjugated dienes
Alipathic cyclic olefins form the that were electrolyzed in acetonitrile-
trans-dimethoxy compound in anodic containing N2 O4 , showed a good regio-
methoxylation; however, only as a minor and a poor stereoselectivity [240]. Anodic
Fig. 46 Stereoselective anodic Ph R2

fluoroacetamidation of Ph R2 −2e−
arylolefins [235–237]. AcHN C C F
F−/MeCN
R1 R3
R1 R3
R1 = R2 = H, R3 = Ph (erythro/threo: 0.28)
R1 = R3 = H, R2 = Ph (erythro/threo: 0.25)
R2 = H, R1 = R3 = Me (erythro/threo: 3.00)
CO2H
R
RCO2H OEt
AcO O OEt −e, −CO2 AcO O
a
R
OEt
AcO O
b
R: CH 3(CH2)7, 54%, a : b 3.0:1
R: PhMe 2SiCH2, 38%, a : b 4.3:1
Fig. 47 Stereoselective 5-exo-trig-cyclization and heterocoupling to a
prostaglandine precursor [246].
H H
O O CH3CO2H
O O
AcO AcO
−2CO2, −2H , −2e
AcO CO2H MeOH, Pt AcO
H
50%
Fig. 48 Stereoselective 5-exo-trig-cyclization and hetereocoupling to a branched
carbohydrate [247].
acetamidosulfenylation occurs stereose- conditions on the regio- and stereoselec-

lectively to form the trans product tivity has been reviewed recently [245].
in acetonitrile-containing disulfides [241, Unsaturated carboxylic acids can be de-
242]. The selenoalkoxylation of cyclic carboxylated to alkyl radicals that undergo
olefins stereoselectively affords the trans an intramolecular addition. The 5-exo-trig-
product with a 56 to 98% yield [243]. cyclization of ß-allyloxy radicals, generated
Optically active 2-fluoro-1-tetralones (with from an appropriate carboxylic acid, com-
>95% ee) were prepared by anodic fluori- bined with a final heterocoupling has
nation of camphanyl enolester derivatives been applied to synthesize a precursor of
and subsequent hydrolysis of the flu- prostaglandine PGF2α (Fig. 47) [246] and a
orinated electrolysis products [244]. The branched carbohydrate (ratio of diastereo-
transformation of alkenes by direct and mers 1.8 : 1) (Fig. 48) [247]. A radical tan-
indirect anodic oxidation and the effect of dem cyclization of a doubly unsaturated
substrate, of structure, and of electrolysis monocyclic carbocyclic acid provides a
short synthetic entry to tricyclic products, and a hydrophobic PTFE-coated electrode

for example, triquinanes [248]. In all these (Fig. 49) [253–256].
reactions, the cyclization proceeds highly The intramolecular cycloaddition of
stereoselectively as an intramolecular cis phenol derivatives can lead stereoselec-
addition, while the concluding intermole- tively to three different product types
cular heterocoupling has a low stereo- (Fig. 50) [257–259]. The competition of
selectivity. the three pathways depends strongly on
Neutral aminyl radicals generated by the configuration of the double bond and
anodic oxidation of lithium alkenyl the nature of the functional groups at-
amides undergo a stereoselective cy- tached to it. The different products can
clization to cis-1-methyl-2,5-disubstituted be formed quite selectively [260]; the syn-
pyrrolidines [249]. thetic possibilities have been summarized
in Ref. [261].
Cycloaddition Anodically generated phe-
noxy cations, o-quinones, and o-quinone 13.4.2.2 Diastereoselectivity at the
methides react with olefins to bicyclic and Cathode
tricyclic annelated compounds in stereos-
elective cycloadditions [250–252]. In the 13.4.2.2.1 Coupling
synthesis of a Euglobal skeleton, a Activated olefins The scope of elec-
quinone methide has been generated trohydrodimerization of activated olefins
in situ by anodic oxidation mediated with regard to the different struc-
by DDQ. The cycloaddition was pro- tures and functional groups has been
moted by the use of lithium perchlorate thoroughly explored since the discoveries
HO OH
a
+
•
O OH
Cl CN Cl CN
O OH 2 2
Cl CN Cl CN
OH HO
−2e
a : PTFE-coated Pt electrode
O O
HO O HO O
O OH O OH
74%
Fig. 49 Cycloaddition of an electrogenerated o-quinone methide to

α-phellandrene [255, 256].
MeO OH 2 MeO O
R R3 −2e, −H+ R2 R3
+
R4 R4
MeO MeO
R1 R5 R1 R5
R2
R1
R2 O
R1 O O R4 R3
O
R5
R3 R5
MeO R3 MeO MeO
R1 R4
R5 O
O
R4 R2
Fig. 50 Stereoselective intramolecular addition of anodically generated phenoxy

cations [257–259].
H5C6 C6H5
O H5C6
+e CO2Me
C6H5 OR a CO2R CO2Me
H5C6
O
a: Hg, DMF, TEAB yield: 69−98% R: different chiral auxiliaries, borneol > 95% de.
b: 1. NaOH, 2. HCl, MeOH, 62−88%.
Fig. 51 Stereoselective hydrodimerization of methyl cinnamate [264–270].
of M. M. Baizer [262, 263] and is presently stereochemistry at C3 and C4 is fixed ir-

still extended (see Chaps. 4 and 7). The reversibly at the coupling stage, and there
strong interest in the stereochemistry is strong evidence that templating in the
of these coupling reactions, however, complex between the two radical anions
started only a decade ago. In this con- and water determines the stereochem-
nection, the stereochemistry of the hy- istry [265, 266].
drodimerization of cinnamic acid ester- With diphenylmethylborneol as the chi-
ified with chiral auxiliaries has been ral auxiliary high face selectivities have
investigated. It proceeds smoothly via been achieved and the all-trans-2-alk-
coupling and intramolecular condensa- oxycarbonyl-3,4-diphenylcyclopentanone
tion. Thereby, highly simple diastereose- has been converted to dimethyl (3R, 4R)-
lectivities to all-trans-2-methoxycarbonyl- 3,4-diaryladipate with 87 to 95% ee [267,
3,4-diphenylcyclopentanone and, in some 268]. With an isopropyloxazolidinone as
cases, highly facial diastereoselectivities the chiral auxiliary the stereoselectivity
(>95% de with bornyl ester) have been in the all-trans cyclized hydrodimer was
found (Fig. 51) [264]. strongly affected by the electrolyte em-
A well-supported mechanism for a rad- ployed [269, 270].
ical anion–radical anion coupling as the A mechanism similar to that for α, β-
key step has been proposed. The relative unsaturated esters has been worked out
for the stereoselective coupling of α, β- dimethyl benzene-1,2-diacrylate by ca-

unsaturated ketones [271]. thodic coupling and subsequent Michael
Methyl 4-t-butylcyclohex-1-enecarboxy- addition [275].
late forms as the major single prod- Methyl abscisic acid undergoes an in-
uct upon cathodic reduction in DMF tramolecular cyclization affording with a
(dimethylformamide) a hydrodimer in 51% yield a mixture of diastereomers
which the cyclohexyl rings are joined ax- (Fig. 52) [276].
ially and the methoxycarbonyl groups are Cathodic reduction of 1,3-diphenyl-
also axial. kinetics and force-field calcu- propenone leads to 1-hydroxy-2-benzoyl-
lations indicate a radical anion–radical 3,4-diphenyl cyclopentanes with exclu-
anion coupling, whose stereoelectronic sive cis configuration of the two phenyl
groups. With 1-phenyl-1-pentene-3-one
control dictates diaxial coupling of the cy-
the cyclodimer 2-methyl-3,5-diphenyl-4-(1-
clohexyl rings. Protonation of the dimer
propionyl)-cyclohexanone is formed with a
dianion is under thermodynamic con-
100% yield in an intramolecular Michael
trol [272]. The cathodic coupling of 2-aryl-
addition via an electrogenerated base. The
1-arylsulfonylethylenes leads in aprotic
substituents are all in the most stable equa-
media and in the presence of lithium salts torial position [277].
almost exclusively to D,L-hydrodimers. Intramolecular hydrodimerization of ac-
The coupling reaction often competes tivated olefins has been exploited for
with cleavage reactions and depends on elegant one-step cyclizations and hetero-
the proton donating ability of the sol- couplings (Fig. 53) [263, 278, 279].
vent [273]. 3-(2-Furyl)propennitrile yields A variety of intramolecular cathodic
a mixture of D,L- and meso-hydrodimers, homo- and heterocouplings and their
from which the latter undergoes an in situ stereochemistry also with regard to the
Thorpe–Ziegler reaction to a cyclic enam- synthesis of complex natural products is
inonitrile [274]. A tetracyclic hydrodimer shown in Fig. 54, and has been compiled
is obtained highly stereoselectively from in Chap. 11 and in Ref. [280].
OH OH
e, CH3CN, HOAc
CO2Me Bu4NOAc, 51%
O O
CO2Me
Fig. 52 Intramolecular cyclization of methyl abscisic acid [276].
CO2CH3 +2e, R4NX CO2Me

CO2CH3 Hg, CH2(CO2Me)2 CO2Me
Yield [%] Trans/cis Additive

82−87 2.6:1 None
73 14.8:1 1eq. CeCl 3
Fig. 53 Stereoselective intramolecular coupling of α, β-unsaturated esters [279].

CN NC CN NC CN
O O
CN 2e, CH3CN
O O
CH2 (CO2Me)2,
Bu4NBr
O H H
O A B
Yield [%] Sse A:B

23 Bu4NBr 1:1
77 LiClO4 3:3
62 Mg(ClO4)2 11:1
Fig. 54 Stereoselective cyclization of activated olefins [281].
Trimethyl aconitate can be cyclodimer- of adsorbable ions such as I− and Et4 N+ ,

ized in 75% yield and a high stereose- the rac/meso ratio for benzaldehyde can
lectivity to a pentamethyl 1-(2-methoxy-2- decrease to 0.5 [284]. In dry DMF/LiClO4 ,
oxoethyl)-1,2,3,4,5-cyclopentane pentacar- the rac/meso ratio for acetophenone in-
boxylate. Product formation is initiated by creases up to between 12.5 and 19 [285].
an electrogenerated base that induces a It was proposed that in acidic solutions,
catalytic cycle of two successive Michael ad- two ketyl radicals couple and in alkaline
ditions. The most stable out of 16 possible solution a ketyl radical and a radical anion
diastereomers is formed, which indicates couple. There is one transition state (11)
that the tandem Michael addition is ther- leading to a meso product and two (12)
modynamically controlled [282]. and (13) forming a rac product. (11) min-
imizes steric interactions, while in (12)
and (13) hydrogen bonding is involved.
Carbonyl compounds
The latter is more or less pronounced in
acidic and basic protic media. In apro-
Intermolecular coupling Many papers on tic media with the complexing Li+ ion,
hydrodimerization of aromatic carbonyl bridging is maximized leading to high rac
compounds have appeared indicating the selectivity.
importance of this reaction. The rac/meso
ratio for the pinacolization of acetophe-
H
none in aqueous ethanol ranges between OH O
0.9 and 1.4 in acidic medium and be- H3C C6H5 H3C O
tween 2.5 and 3.2 in basic medium. H
The diastereoselectivity is independent H5C6 CH3 H5C6 CH3
OH C6H5
of the cathode material mercury, tin,
(11) (12)
or copper. Electrolysis conditions such
as current density, potential, or current- H
O
controlled electrolysis also do not influence O C6H5
the diastereoselectivity. The same holds H
for propiophenone. For benzaldehyde, the C6H5 CH3
rac/meso ratio is 1.1 to 1.2 in acidic as well CH3
as in basic media [283]. In the presence (13)
For further contributions on the dia- medium. These couplings need more neg-
stereoselectivity in electropinacolizations, ative reduction potentials than aromatic
see Ref. [286–295]. Reduction in DMF at carbonyl compounds and suffer from com-
a Hg cathode can lead to improved yield peting aldol reactions.
and selectivity upon addition of catalytic Unconjugated unsaturated aliphatic ke-
amounts of tetraalkylammonium salts to tones undergo a regio- and diastereose-
the electrolyte. On the basis of preparative lective intramolecular heterocoupling in-
scale electrolyses and cyclic voltammetry volving the addition of a ketyl to the
for that behavior, a mechanism is pro- double bond (Fig. 20) [111]. An interest-
posed that involves an initial reduction ing extension is the twofold cyclization
of the tetraalkylammonium cation with of unconjugated dienones to form bi-
the participation of the electrode mate- cyclic alcohols in high yield and stereose-
rial to form a catalyst that favors 1e lectivity (Fig. 55) [303]. (+)-N,N -dimethyl-
reduction routes [296, 297]. Stoichiomet- quinium tetrafluoroborate causes an anod-
ically shifted catalytic current and is essen-
ric amounts of ytterbium(II), generated by
tial for double cyclization. It is proposed
reduction of Yb(III), support the stereospe-
that it is adsorbed at the cathode and facil-
cific coupling of 1,3-dibenzoylpropane to
itates reduction and exo-trig-cyclization by
cis-cyclopentane-1,2-diol. However, Yb(III)
hydrogen bonding.
remains bounded to the pinacol and can-
Imines can be stereoselectively hy-
not be released to act as a catalyst. This
drodimerized to 1,2-diamines with rac/
leads to a loss of stereoselectivity in the
meso ratios of 0.9 to 1.1 similar to the
course of the reaction [298]. Also, with the cathodic coupling of carbonyl compounds
addition of a Ce(IV)-complex the stereo- to pinacols in an acidic medium [304].
chemical course of the reduction can be With 4,6-dimethylpyrimid-2-one only the
altered [299]. In a weakly acidic solution, meso-diamine was obtained [305]. Elec-
the meso/rac ratio in the EHD (electrohy- troreduction of diimines prepared from
drodimerization) of acetophenone could 1,2-diamines and aromatic aldehydes gave
be influenced by ultrasonication [300]. Be- 2,3-diaryl piperazines in DMF/TEATos
sides phenyl ketone compounds, examples and MSA (methane sulfonic acid) in high
with other aromatic groups have also been yield and with stereoselectivity. Chiral
published [294, 295, 301, 302]. piperazines were prepared from chiral 1,2-
There is insufficient information on diamines [306]. With a steel cathode and
the stereochemistry of the experimen- a sacrificial Al anode in TFA (tetraflu-
tally less simple hydrodimerization of oroacetyl), PbBr2 , and Bu4 NBr/THF as
aliphatic carbonyl compounds in a protic electrolyte with a 65 to 77% yield, and
O− OH
O
+e H+, +e
a H+
•
H H
65%
a: DMF, i-propanol, (+)−N,N ′-dimethyl-quinium tetrafluoroborate.
Fig. 55 Stereoselective twofold cyclization of unconjugated dienones to bicyclic
alcohols [303].
1,2-diamines were obtained with rac:meso 1,4-diols with a good yield (78–79%). The
ratios >99 : 1 by using the sterically use of a chiral allyl alcohol gave the diol
demanding N -benzhydryl-N -benzylidene with a high diastereomeric excess (de >
amines [307]. 85%) The diastereoselectivity is explained
Reductive cross-dimerization has been as being due to hydrogen bonding between
established with ketones and O-meth- the hydroxyl group of the alcohol and the
oximes upon reduction in isopropanol with ketyl derived from the ketone [309].
a Sn cathode as a convenient route to β-
amino alcohols, diastereoselectivities of up
to 85 : 15 were obtained. A chiral ligand Intramolecular coupling Some aromatic
was obtained this way from the cou- diketones have been stereoselectively cy-
pling of (–) – menthone with O-methyl clized under various electrolysis condi-
acetaldoxime. Similarly, ketones could be tions, which, together with the substrate
coupled to hydrazones and nitrones. Also, structure, strongly influence the stereo-
intramolecular couplings were achieved chemistry of the formed cyclic diol. Reduc-
with good yields and diastereoselectivity tive cyclization of 1,8-diaroylnaphthalenes
(Fig. 56) [308]. led to trans-diols, 2,2 -diaroylbiphenyls and
Cathodic heterocoupling of ketones with α, ω-diaroylalkanes yielded cis-diols with
allylic alcohols takes place at a carbon fiber different stereoselectivities depending on
cathode with high regio- and diastereo- substrate structure and electrolysis condi-
selectivity to afford the corresponding tions (pH, cosolvent) (Fig. 57) [310–312].
OCH3
OCH3
ON HO N
H
2e, +2H+ H
Sn, i-PrOH,
( )n TEATos ( )n
n Yield (%) trans:cis
1 65 95:5
2 72 85:15
Fig. 56 Stereoselective intramolecular coupling of a carbonyl group with

an O-methyl oxime [308].
2e−, +2H+
R3
R1 R2
R1 C R3 C R2
HO OH
O O
R1 R2 R3 Yield [%] cis/trans-OH
C6H5 C6H5 CHMe 80 cis only
C6H5 C6H5 CMe2 80 cis only
C6H5 Me CHMe 80 1
4-CH3OC6H4 4-CH3OC6H4 (CH2)3 82 26
4-HOC6H4 4-HOC6H4 (CH2)3 89 0.9
4-CH3OC6H4 4-CH3OC6H4 (CH2)4 64 cis only
Fig. 57 Stereoselective intramolecular coupling of ketones to cyclic
diols [313, 310].
2-Substituted 1,3-diphenyl-1,3-propanedi- using a Sn cathode and tetraalkylammo-

ones afforded in high yield and cis selecti- nium salts in isoPrOH (Fig. 58). A variety
vity 3-methyl substituted 1,2-diphenyl-1,2- of new bi- and polycyclic tertiary alcohols
cyclopropanediols [313]. 1-Acyl-9-benzoyl- were prepared this way. Mechanistic stud-
naphthalenes were cyclized to 1,2-acena- ies point to a reduction of the carbonyl
phthenediols with a 50 to 100% yield group to a radical anion that attacks the
and a cis:trans ratio ranging from 100 : 0 aromatic ring in such a way that the
(preferably in an acidic medium) to 0 : 100 negatively charged oxygen atom avoids
(preferably in a basic medium), which is electronic repulsion with the π-electrons
also dependent on the kind of acyl group, of the aromatic ring leading this way to the
supporting electrolyte, cosolvent, and cath- product with H and OH being cis to each
ode potential. The preferable formation other. Reduction with Na in HMPA (hex-
amethyl phosphoric acid triamide)-THF
of the cis-diol in an acidic medium is
gave the same cyclized product; however,
rationalized as due to cyclization in a rad-
in lower yield than in the electroreduc-
ical–radical coupling, while in an alkaline
tion [317, 318].
medium, the trans-diol is formed by in-
1-(Oxoalkyl)pyridinium salts can be cy-
tramolecular nucleophilic addition of the
clized to quinolizidine and indolizidine
radical anion to the carbonyl group [314]. derivatives upon reduction in aqueous sul-
Electroreduction of γ - and δ-cyano ke- furic acid at a Hg cathode. The cyclization
tones in isoPrOH with a Sn cathode gave occurs in some cases with high stereoselec-
α-hydroxyketones with good diastereo- tivity. The stereochemistry of the products,
selectivities as cyclization products. The cyclic voltammetry, and quantum chemi-
reaction has been used as a key step for cal calculations point to a reduction of
the synthesis of, for example, guaiazulene, the protonated carbonyl group forming a
triquinanes, and dihydrojasmone. Simi- nucleophilic radical that adds to the elec-
larly, the corresponding intermolecular trophilic C=N bond of the pyridinium moi-
couplings were realized [315]. ety. The cyclized radical cation is further
Nonconjugated enones and ynones that reduced to the products. The stereoselec-
contain a sulfur or nitrogen bridge could tivity can be correlated with the energies
be regio- and diastereoselectively hy- of the cyclized diastereoisomeric radical
drodimerized to cyclic alcohols [316]. cations, which indicates that the cycliza-
Reduction of nonconjugated aromatic tion is reversible (Fig. 21) [115].
ketones gave at metal cathodes (e.g., tin,
copper, silver, palladium, zinc) the cis iso- Halides The nickel-catalyzed cathodic
mers (cis-H/OH) of cyclized products in addition of (Z)- or (E)-alkenylhalides
high diastereoselectivity. The electroreduc- to electron-deficient olefins in the pre-
tion of 5-phenylpentan-2-one led to 70% sence of a sacrificial iron rod anode
of an exclusively cis-hexahydronaphthalene proceeds with complete retention of
O Me OH
H
Sn, i-PrOH Fig. 58 Cathodic
stereoselective cyclization of
Et4NTos
nonconjugated aromatic
70% ketones [317, 318].
the stereochemistry in the alkenyl part controlled and occurs with little face
and affords isomerically pure (Z)- and selectivity [322].
(E)-olefins in high yield [319]. Aryl-O- The stereochemical outcome of cathodic
glycosides have been prepared diastereos- hydrogenation of acetylenes to the cor-
electively by cathodic reduction of glycosyl responding alkenes changes strongly with
halides at a Ag cathode with a set of phenols the reaction conditions, such as supporting
and polyhydroxyphenols [320]. electrolyte, solvent, and cathode material.
A Ag/Pd-cathode hydrogenates 2-butyne-
1,4-diol and acetylene dicarboxylic acid
13.4.2.3 Hydrogenation
exclusively to the cis-olefin [323]. Simi-
lar results were obtained at a Cu net
C, C double and triple bonds C=C dou- covered with spongy silver [324]. With
ble bonds can be stereoselectively hydro- dimethyl butynedioate the cis/trans ra-
genated with cis or trans addition of the hy- tio of the product dimethyl butenedioate
drogen atoms. 2,3-Diphenylindenone un- on a Pd black cathode decreased with
derwent a selective cis addition in 0.25 M increasing pH both in electrolytic and cat-
sulfuric acid, while a trans addition was alytic hydrogenation [325]. On the other
found at higher pH values (Fig. 59) [321]. side at a Hg cathode a trans addi-
For the corresponding methyl-phenyl- and tion to alkynes occurs [326]. In methy-
dimethylindenone, the diastereoselectivity lamine/LiCl, dialkylacetylenes are reduced
was low. to trans-olefins. Nonconjugated aromatic
The cis/trans ratio of 1,4-disubstituted internal acetylenes are selectively reduced
cyclohexanes formed from activated cyclo- to aromatic trans-olefins [327].
hexenes at a Hg cathode depends on the Electrolysis of estratetraene (B) (Fig. 60)
solvent and proton source and shows a in acidic EtOH at 20 ◦ C and a catalyt-
low diastereoselectivity. Protonation of the ically active electrode (Pd on Pt cath-
first formed radical anion is kinetically ode) gives 8α-estradiol methyl ether (C)
Ph Ph
2e−, +2H+
C Ph C Ph
Fig. 59 Stereoselective O O
cathodic hydrogenation of 100% cis in 0.25 M H2SO4
2,3-diphenylinden-1-one [321]. 100% trans at pH 4.7–9.3
OH OH OH
H H
80 °C 20 °C
H H
MeO MeO MeO
(A) (B) (C)
Fig. 60 Stereoselective hydrogenation of estratetraene (B) in acidic EtOH at a Pd/Pt cathode at 80
and 20 ◦ C [328].
stereoselectively. At a higher temperature and trans isomers of the corresponding

(80 ◦ C) and otherwise identical conditions, cyclohexanecarboxylate. The isomer ratio
the 8-β-product (A) is formed stereoselec- depends on the reaction conditions and is
tively, which results from the acid catalyzed under kinetic control. Protonation of the
isomerization of the 8,9-double bond at the first formed radical anion occurs probably
higher temperature. Also, nonconjugated at C1 with little stereoselectivity [322].
double bonds are reduced, while carbonyl
groups are not attacked [328].
C=X bonds The stereochemistry of the
Reduction in liquid NH3 and NaCl at Pt
reduction of carbonyl compounds has
electrodes gives a 90% yield of a mixture
been intensely studied with regard to
consisting of 85% (A) (Fig. 60) and 14%
synthetic and mechanistic aspects. The
(C) [329]. The hydrogenations in methy-
reduction of 1,2-diphenyl-1-propanone at
lamine or ammonia are cathodic Birch
a Hg cathode in aqueous EtOH and
reductions in which the final protonation
of the intermediate anion leads to the pH 8 affords the erythro alcohol as
thermodynamically more favorable trans the major diastereomer (erythro:threo =
product. 5 to 1.4 : 1) [332]. This selectivity is in ac-
A benzene ring without electron- cord with a protonation of the intermediate
withdrawing substituents is hydrogenated anion, formed in an ECE sequence, from
by using hydrogen active cathodes in the least hindered side (Fig. 61).
an acidic solution. For example, O- The cathodic reduction of ketones (±)-
methylphenol is stereoselectively hydro- RCHMeC(O)R1 (R = Ph, R1 = Ph, Me;
genated on a Rh/C cathode to give R = cyclohexyl, R1 = Me) afforded mix-
cis-2-methylcyclohexanol (cis/trans ratio tures of diastereomeric alcohols. The
2.3–6.7) as the major isomer. 2,6- origin of the diastereoselectivity, which de-
Dimethylphenol affords cis,cis-2,6-dime- pends on R1 and R and the electrolysis
thylcyclohexanol [330]. Enantioenriched conditions, is discussed [333]. Acyclic and
substituted (R)-4-phenylpyridine has been cyclic ketones with a chiral center in the
reduced to the corresponding (S)-4- ß-position yielded diastereomers in a ratio
phenyl-1,4-dihydropyridine with partially different from that obtained by LiAlH4 -
high retention of configuration depend- reduction [334].
ing on the substituents [331]. Methyl 4-t- 4-t-Butylcyclohexanone is reduced at a
butylcyclohex-1-enecarboxylate leads to cis Pt black cathode to 4-t-butylcyclohexanol
OH
O CH3
+e, H+
PHC CH(CH3)Ph Ph C
+e H+
H
Ph
OH Ph
CH3
H OH
Ph H
H CH3
H
Ph Ph
Fig. 61 Stereoselective reduction of 1,2-diphenyl-1-propanone to
erythro-1,2-diphenyl-1-propanol as the major diastereomer (other
enantiomer not shown) [332].
with a cis/trans ratio of 0.9 in acidic and example, 4-t-butylcyclohexanone, trans-

1.0 in basic media. At a Hg cathode the decalin-2-one and others have been inves-
corresponding ratios are 0.2 and 0.4 [335]. tigated looking particularly at factors (e.g.,
For 2-methylcyclohexanone, the cis/trans cathode material, solvent, proton donor,
ratio of the formed 2-methylcyclohexanol cathode potential, current density, and
depends on the electrode material, cur- supporting electrolyte) that influence the
rent density, cosolvents and pH of the ratio of ax:eq alcohol. The highest stereos-
electrolyte. In a basic medium, the best electivity in favor of the axial alcohol (98%
yields were obtained with a cis/trans ratio cis alcohol from 4-t-butyl-cyclohexanone)
of 35 : 65 [336]. For 4-t-butylcyclohexanone is obtained using doubly charged elec-
and 3,3,5-trimethylcyclohexanone at a Pt trolyte cations (Mg2+ , Zn2+ ). The control
cathode in LiCl, EtOH, and HMPA, a good of stereochemistry is explained in terms of
yield of the alcohol with a eq/ax ratio of ion-pairing of the key carbanionic interme-
diate that is formed in an ECE process. Fur-
95 : 5 was obtained, while at a Pb cathode
ther investigations of the stereoselective re-
in NaOAc, HOAc, MeOH a lower yield and
duction of ketones are found in [341, 342].
a eq/ax ratio of 44/56 was observed [337].
For steroidal ketones and α-ketols, stere-
A series of cyclic ketones was reduced
oselective cathodic reductions have been
in isopropanol and in H2 SO4 , H2 O, and
described [343]. The stereoselective reduc-
MeOH. It was found that in isopropanol the
tive ring opening of epoxyketones to a ke-
ratio of diastereomers was approximately toalcohol has been used in the conversion
equal to their relative thermodynamic sta- of the corresponding steroids [344, 345].
bilities, while in an acidic medium, the The reduction of 2-oxoacids bound to
less stable epimeric alcohols were formed different chiral auxiliaries gave the 2-
to a higher extent. This result was taken hydroxyacid derivatives in a 64 to 76%
as an indication that in an acidic medium yield and 42 to 86% de depending
an adsorbed intermediate is rapidly proto- on solvent, proton donor, supporting
nated, while in the poor proton donating electrolyte, temperature, and substituent
isopropanol, this intermediate can dif- R in the oxoacid. The results are in
fuse into solution and equilibrate in this accordance with an ECE reduction of the
way [338]. A very profound study gives 2-oxoamide to an enolate anion, which
further insight into the mechanism [339, subsequently undergoes a face-selective
340]. Conformationally rigid ketones, for protonation to the hydroxy acid [346, 347].
R R R R R R
Hg, +4e
CH3OH, H2O, LiCl NH2 +
R NOH R R NH
2
50–70%
R Rel. yields
[%]
H 0 100
CH3 99 1
Fig. 62Stereoselective reduction of camphor- and
norcamphoroxime [348].
Electrochemical reduction of camphor- Cathodic deprotection of tosylates of

and norcamphoroxime at a Hg cathode chiral alcohols was achieved without
proceeds with a high degree of stereo- racemization by cleavage of the O−SO2
selectivity to give products of opposite bond [351]. Optically active quaternary
stereochemistry to those formed in the arsonium [352, 353] and phosphonium
dissolving metal (Na-alcohol) reduction of salts [354] are cathodically cleaved to ter-
the oximes. The electrolyses are proposed tiary arsines and phosphines respectively,
to proceed by a kinetically controlled attack with retention of the configuration. The
by the electrode on each oxime from the first enantiomer enriched chiral phos-
less hindered side (Fig. 62) [348]. In con- phines have been prepared this way.
trast, the corresponding N-phenyl imines 1-Substituted 2,2-dibromocyclopropanes
yield products of the same stereochem- are stereoselectively reduced to the corres-
istry as those isolated from a dissolving ponding diastereomeric monobromides in
metal reduction. Cyclic voltammetry and good yields (Fig. 63) [355].
polarographic data point to RH− and R2− Bicyclic gem-dihalocyclopropanes lead
intermediates in this case that are proto- predominantly to the corresponding
nated from the least hindered side [349]. endo-monohalocyclopropanes, which are
Reductive cathodic amination of 2,5- formed by reduction of the exo-halogen,
hexanedione with ammonia and 1-pheny- whose approach to the cathode is less
lethylamine at the Hg cathode gave hindered [356, 357].
2,5-dimethylpyrrolidines with satisfactory Cathodic reduction of bicyclic gem-
yields and excellent cis selectivity dibromocyclopropane in the presence of
chlorotrimethylsilane provides the exo-
(90–98%). Other amines reacted less
silylated isomer selectively. With a sac-
selectively to afford mixtures of pyrroles
rificial Mg anode the current efficiency
and diastereoisomeric pyrrolidines. A
can be increased by sonication as the
mechanism is proposed that involves the
anode acts additionally as a chemi-
reduction of iminium ions, in which the
cal reducing agent [358]. The 2e re-
stereoselectivity is controlled after the two
duction of (S)-(+)-1-bromo-1-carboxy-2,2-
1e reductions of the cyclic iminium ion by
diphenylcyclopropane showed that the
the final protonation [350].
stereoselectivity at a Hg cathode was
strongly determined by the supporting
13.4.2.4 Cleavage electrolyte cation. With NH4 + , a pre-
In cathodic cleavage, a C−X bond is mostly ferential retention of configuration was
reduced to a radical anion that dissociates observed, which increased with a more
into a radical and an anion X− . The negative reduction potential. By contrast,
radical is further reduced to an anion and a R4 N+ cation gives rise to a major inver-
protonated in the final step. sion, which increases with the bulkiness
Br R1 2e− H R1 Br R1
+
+H+, −Br−
Br R2 Br R2 H R2
cis trans Fig. 63 Diastereoselective
debromination of substituted
R2: Ph R 1: H up to 84% cis
gem-dibromocyclopropanes
R2: CO 2H, CO2Me; R 1: H, Ph 92–99% cis [355].
of the organic cation. The stereochem- anti-configuration. At sufficiently nega-

istry is thought to be determined by the tive potentials, all rotamers were reduced
facial selective protonation of the final under diffusion control such that the
anion, whose orientation and shielding product ratio reflected the distribution of
is also controlled by the nature of the the conformers in the dibromide [363].
interface [359]. Cyclic quaternary enam- The double bond in unsaturated car-
monium salts undergo a electroreductive boxylic acids and alcohols was protected
ring opening to enamines, that are further by bromination with pyridinium hydrobro-
reduced to cyclic amines, whose stere- mide perbromide under mild conditions.
oselectivity is affected by the pH of the Deprotection was achieved by cathodic re-
electrolyte [360]. duction at −1.4 V. At overall yields of 68
to 99%, the configuration of the dou-
13.4.2.5 Elimination ble bond was retained by >96% [364].
Cathodic elimination occurs with vicinal The reductive elimination of the cyclic
C−X bonds that can act both as an elec- sulfate of 1,2-butanediol led to trans-2-
tron acceptor and as a leaving group. butene selectively. Aromatic vicinal diox-
Vic-dihaloalkanes were stereoselectively alates underwent fragmentation and elim-
reduced at a Hg cathode to the cor- ination on cathodic reduction to give
responding olefins. Meso-1,2-dibromo-1,2- alkenes. Meso-(EtO2 COCH(C6 H5 ))2 gave
diphenylethane gave trans-stilbene only. 80% trans-stilbene [365].
The rac compound afforded cis- and trans-
stilbene, with the cis portion increasing 13.4.3
with size and concentration of the sup- Enantioselectivity
porting electrolyte cation. This has been
interpreted as being caused by interaction 13.4.3.1 General
of this cation with an anionic inter- A reaction is termed enantioselective when
mediate [361]. 2,3-Meso-dibromosuccinate a new stereogenic center is generated and
has been reduced stereoselectively to fu- one enantiomer is formed in excess. This
marate and maleates. The rac form se- occurs through a chiral inductor that is
lectively produced fumarate at low and in a reversibly formed complex attached
high pHs, while between pH 0.4 and to the molecule that bears the prostere-
6.9, up to 70% maleate is formed. A ogenic center. The chiral inductor can
mechanism explaining this behavior is be in the reagent, the solvent, in addi-
presented [362]. The cathodic reduction tives, or, in the case of heterogeneous
of the meso and rac forms of EtCH- reactions, at a surface. Best suited are
BrCHBrEt and Me2 CHCHBrCHBrCH- enantioenriched catalysts, whose stereo-
Me2 was carried out in liquid am- chemical information is transferred to the
monia and DMF. The cis/trans ra- substrate in the rate-determining step.
tio of the products EtCH=CHEt and A large number of efficient enantios-
Me2 CHCH=CHCHMe2 varied with the elective catalysts have been developed
electrode potential. Elimination of two in organic chemistry that lead to enan-
bromide anions occurred preferentially tioselectivities >95% ee for functional
by a concerted mechanism, except for group interconversions, especially hydro-
the rac diastereomer of the latter dibro- genations, and many types of C, C – bond-
mide, which was unable to attain the forming reactions [184, 185]. In organic
electrochemistry, enantioselective conver- current for (R)-1-phenylethanol compared

sions are much less developed than those with a small enhancement for the (S)-
in chemical synthesis. Nevertheless, there isomer [369]. This oxidation was also per-
are some methods and potential develop- formed free of organic solvents in an
ments that are outlined below. aqueous silica gel disperse system to
afford enantioenriched sec-alcohols and γ -
13.4.3.2 Anode lactones [370].
In an enantiomer-differentiating oxida-
13.4.3.2.1 Coupling A graphite felt elec- tion at a poly-(L-valine)-coated PbO2 an-
trode chemically modified with TEMPO ode, rac-2,2-dimethyl-1-phenyl-1-propanol
led to the enantioselective electrocatalytic was partially oxidized leaving 43% opti-
coupling of 2-naphthol, 2-methoxynaphth- cally pure (S)-alcohol [371]. At a TEMPO-
alene and 10-hydroxyphenanthrene with modified graphite felt anode rac-1-phenyl-
high enantioselectivity (up to 98% ee) in ethanol has been enantioselectively oxi-
the presence of (–)-sparteine as a chiral dized in the presence of (–)-sparteine
base [366]. leaving 46% of the (R)-alcohol with 99.6%
ee [372]. However, under the same con-
13.4.3.2.2 Addition Anodic oxidation ditions, an exclusive dehydrogenation of
of enolacetates, for example, 1-acetoxy- (–)-sparteine to the iminium salt without
3,4-dihydronaphthaline and α-acetoxy-β- oxidation of the alcohol was found [373].
alkylstyrene, afforded at −78 ◦ C in ace- Alkyl aryl sulfides were anodically ox-
tonitrile/THF/HOAc containing tetraethy- idized to the corresponding chiral sul-
lammonium (S)-camphorsulfonate as foxides by using poly(amino acid)-coated
supporting electrolyte, enantioenriched electrodes. Partially very high enantioselec-
acetoxylation products with 44 and 21% tivities (93% ee) were reported [374, 375];
ee (enantiomeric excess) respectively [367]. however, the reproducibility depended
strongly on the lot of the poly(amino
acid) used [376]. Earlier, with a similar ap-
13.4.3.2.3 Heteroatom Oxidation, De-
proach, by using an edge surface graphite
hydrogenation Electrooxidative kinetic
anode that was chemically modified with
resolution of rac alcohols mediated with
(S)-phenylalanine, an enantioselectivity of
a catalytic amount of an optically active
0.5 to 2.5% was found in the oxidation of
N -oxyl was performed in an undivided
methylp-tolyl sulfide to the sulfoxide [377].
cell at constant current conditions. A
high enantiomeric purity for the recov-
ered alcohol was found, which could be 13.4.3.3 Cathode
increased by electrolysis at lower tem-
peratures. The optically active N -oxyl 13.4.3.3.1 Hydrogenation The enantio-
was recovered and used repeatedly with- selective reduction of prochiral ketones
out change in efficiency and selectiv- to chiral alcohols has been intensely in-
ity [368]. Cyclovoltammetry with the N - vestigated. The highest enantioselectivity
oxyl: (6R, 7S, 10R)-4-oxo-2,2,7-trimethyl- has been found for 2-acetylpyridine, which
10-isopropyl-1-azaspiro[5.5]undecane-N - was reduced in buffered EtOH (pH 4.5), in
oxyl as catalyst showed for rac-1- the presence of strychnine to 1-(2-pyridyl)-
phenylethanol a highly enhanced catalytic ethanol with 48% ee. The selectivity was
assumed to arise by enantioselective proto- arises among others from a specifically ad-
nation of (PyrC(OH)CH3 )− formed in an sorbed supporting electrolyte that forms
ECE process from 2-acetylpyridine [378]. H-bonds with the substrate. The high-
For enantioselective conversions involv- est optical inductions were obtained with
ing intermediate carbanions, the influ- certain diquaternary salts [386]. Low enan-
ence of the chiral inductor acting as tioselectivities have been obtained in the
proton donor and the potential that con- reduction of aryl alkyl ketones in the pres-
trols adsorption of the inductor are dis- ence of chiral supporting electrolytes de-
cussed for the electroreduction of syn- and rived from, for example, ephedrine [387].
anti-HON=CPhCO2 H, PhCOCO2 H, and The C=C double bond in 4-methylcou-
PHNHN=CPhCO2 H in the presence of marin has been hydrogenated at a Hg
strychnine [379]. The ee depended on the cathode in the presence of alkaloids with
alkaloid concentration [380–382]. 17% ee [388]. By systematic variation of pH,
The HOPG (highly oriented pyrolytic supporting electrolyte, working potential,
graphite) carbon electrode chemically substrate, and alkaloid (yohimbine)
modified with (S)-phenylalanine at the concentration, the enantioselectivity has
basal surface led to 2% ee in the reduction been increased to 67% ee. A mechanism
of 4-acetylpyridine [377]. A cathode mod- supported by electroanalytical data and
preparative scale electrolysis is proposed.
ified with a chiral poly(pyrrole) reduced
The main features are a 1e reduction of
4-methylbenzophenone or acetophenone
the hydrogen-bonded enone leading to an
in DMF/LiBr and phenol as proton donor
enol radical that tautomerizes to a more
to 1-phenylethanol with up to 17% ee [382].
easily reducible keto radical or dimerizes.
Alkyl aryl ketones have been reduced to the
The keto radical is reduced and further
corresponding alcohols at a Hg cathode in
protonated. The function of yohimbine-
DMF/water in the presence of (1R, 2S)-
H+ is to catalyze the tautomerization
N ,N -dimethylephedrinium tetrafluorobo-
and to enantioselectively protonate the
rate (DET), producing (S)-1-phenylethanol final carbanion. It is also concluded
with 55% ee from acetophenone. Cy- that the hydrophobic yohimbine is
clovoltammetry supports an enantiose- enriched near the hydrophobic cathode
lective protonation of the intermediate surface. Quantum chemical calculations
(PhCOH(CH3 ))− [383]. demonstrate that si protonation of
The asymmetric reduction of C=N dou- the intermediate anion by yohimbine-
ble bonds in prochiral oximes afforded H+ to give the (R)-dihydroproduct is
a maximum of 18% ee [380, 384, 385]. energetically favored [389, 390]. Similarly,
Prochiral azomethines were reduced to 3-methylinden-1-one in the presence of
the corresponding 1,2-diamines and sec- strychnine yields 71% 3-methylindan-
ondary amines using 36 optically active 1-one with 35% ee (S-enantiomer).
supporting electrolytes. The dimers were An analogous mechanism, such as
optically inactive, while the monomers for 4-methylcoumarin, is supported
showed low optical inductions (≤11% ee). by preparative scale electrolysis and
The effect of electrolyte, substrate con- cyclovoltammetry. The mechanistic model
centration, temperature, pH, and cathode enabled the synthesis of simple
potential on the induction was studied. It nonracemic catalysts, from which (S)-
was proposed that the enantioselectivity N -methylprolinooctadecylester leads to
66% 3-methylindan-1-one with 26% 3. I. Fleming, Frontier Orbitals and Organic

ee(S) [391]. Chemical Reactions, Wiley, Chichester, 1978.
4. H. Mayr, B. Kempf, A.R. Ofial, Acc. Chem.
The enzymatic enantioselective hydro- Res. 2003, 36, 66–77.
genation of enoates has been achieved with 5. B. Giese, Angew. Chem. 1977, 16, 125–136.
an enoate reductase and a cathodically re- 6. A. Pross, Adv. Phys. Org. Chem. 1977, 14,
generated methyl viologen radical cation 69–132.
7. P. Rys, Angew. Chem. 1977, 16, 807–817.
as cofactor [392]. This way sodium (E)- 8. P. Rys, Acc. Chem. Res. 1976, 9, 345–351.
2-methylcinnamate was reduced to (R)-2- 9. Ch. Amatore in Basics Concepts in
methyl-3-phenylpropionic acid with 95% Organic Electrochemistry (Eds.: H. Lund,
ee. A number of chiral compounds were O. Hammerich), Marcel Dekker, New York,
2001, pp. 1–94, Chap. 1.
correspondingly prepared via biocatalytic
10. O. Hammerich in Methods for Studies of Elec-
reduction with hydrogenases or reduc- trochemical Reactions in Organic Electrochem-
tases or microbial cells containing those istry (Eds.: H. Lund, O. Hammerich), Mar-
and mediators as cofactors, which were re- cel Dekker, New York, 2001, pp. 85–152,
generated at the cathode [393]. Similarly, Chap. 2.
11. Ch. Amatore in Relations Between Micro- and
electroenzymatic reduction of ketones and Macrophenomena in Organic Electrochemistry
aldehydes using alcohol dehydrogenase af- (Eds.: H. Lund, O. Hammerich), Marcel
forded almost optically pure chiral alcohols Dekker, New York, 2001, pp. 183–205,
in high yields [394]. A high enantioselec- Chap. 3.
12. A. Hembrock, H.J. Schäfer, G. Zimmer-
tivity was also achieved using Baker’s yeast mann, Angew. Chem. 1985, 24, 1055–1056.
and the viologen radical cation as media- 13. H.J. Schäfer in Chemistry of Alkanes and
tor [395]. Electroenzymatic syntheses are Cycloalkanes (Eds.: S. Patai, Z. Rappoport),
reviewed in Ref. [396]. Wiley, Chichester, 1992, pp. 781–808.
14. H.J. Schäfer, E. Cramer, A. Hembrock,
et al. in Electroorganic Synthesis, Festschrift
13.4.3.3.2 Cleavage Gem-dihalides and for Manuel M. Baizer (Eds.: R.D. Little,
monohalides have been dehalogenated to N.L. Weinberg), Marcel Dekker, New York,
1991, pp. 169–180.
chiral monohalides in the presence of al- 15. J.Y. Becker, L.R. Byrd, L.L. Miller et al., J.
kaloids [397, 398]. 1,1-Diphenyl-2-bromo- Am. Chem. Soc. 1975, 97, 853–856.
2-carboxyl (bromo or methyl carboxylate) 16. K. Nyberg in Encyclopedia of Electrochemistry
cyclopropanes are cathodically debromi- of the Elements (Eds.: A.J. Bard, H. Lund),
Marcel Dekker, New York, 1978, pp. 43–70,
nated in the presence of alkaloid cations Vol. XI, pp. 60–61.
with enantioselectivities up to 45% ee. A 17. H. Pütter in Industrial Electroorganic Chem-
mechanism is proposed whereby the alka- istry in Organic Electrochemistry (Eds.:
loid is adsorbed at the Hg cathode, which H. Lund, O. Hammerich), Marcel Dekker,
New York, 2001, Chap. 31, pp. 1259–1307,
protonates face selectively the carbanion pp. 1286–1291.
generated by 2e reduction from the bro- 18. D. Degner, Top. Curr. Chem. 1988, 148,
mide [399]. 1–95, there 17–22.
19. K. Ponsold, H. Kasch, Tetrahedron Lett.
1979, 4463–4464.
References 20. E. Laurent, B. Marquet, R. Tardivel, Tetra-
hedron 1991, 47, 3969–3980.
1. A. Hassner, J. Org. Chem. 1968, 33, 21. A.J. Baggaley, R. Brettle, J. Chem. Soc. C
2684–2686. 1968, 2055–2059.
2. C.D. Ritchi, Physical Organic Chemistry, 22. K.C. Möller, H.J. Schäfer, Electrochim. Acta
Marcel Dekker, New York, 1990. 1997, 42, 1971–1978.
23. A. Guirado, G.P. Moss, J.H.P. Utley, J. 49. B. Wermeckes, F. Beck, H. Schulz, Tetrahe-
Chem. Soc., Chem. Commun. 1987, 41–42. dron 1987, 43, 577–583.
24. T. Shono, Y. Matsumura, K. Hibino et al., 50. S. Kashimura, H. Yamashita, Y. Murai
Tetrahedron Lett. 1974, 1295–1298. et al., Electrochim. Acta 2002, 48, 7–10.
25. T. Shono, A. Ikeda, Y. Kimura, Tetrahedron 51. T. Shono, Y. Matsumura, O. Onomura
Lett. 1971, 3599–3602. et al., Synthesis 1987, 1099–1100.
26. EP 21769, Sumitomo; Chem. Abstr. 1981, 52. J. Cramer, DE 3000 243, Hoechst; Chem.
95, 43412. Abstr. 1981, 95, 140 904j.
27. S. Torii, H. Tanaka, N. Saitoh et al., Tetra- 53. M. Hasegawa, H. Ishii, T. Fuchigami, Tetra-
hedron Lett. 1981, 22, 3193–3196. hedron Lett. 2002, 43, 1503–1505.
28. N.L. Weinberg, E.A. Brown, J. Org. Chem. 54. K.D. Ginzel, E. Steckhan, D. Degner, Tetra-
1966, 31, 4058–4061. hedron 1987, 43, 5797–5805.
29. T. Shono, H. Hamaguchi, Y. Matsumura, J. 55. A. Medici, P. Pedrini, A. De Battisti et al.,
Am. Chem. Soc. 1975, 97, 4264–4268. Steroids 2001, 66, 63–69.
30. T. Shono, Y. Matsumura, K. Inoue et al., J. 56. M. Yoshikawa, T. Murakami, N. Yagi et al.,
Am. Chem. Soc. 1982, 104, 5753–5757. Chem. Pharm. Bull. 1997, 45, 570–572.
31. J.E. Barry, M. Finkelstein, E.A. Mayeda 57. T. Fuchigami, K. Yamamoto, A. Konno,
et al., J. Org. Chem. 1974, 39, 2695–2699. Tetrahedron 1991, 47, 625–634.
32. J.Y. Becker, L.L. Miller, F.R. Stermitz, J. 58. M. Kimura, K. Koie, S. Matsubara et al., J.
Electroanal. Chem. 1976, 68, 181–191. Chem. Soc., Chem. Commun. 1987, 122–123.
33. (a) T. Fuchigami, S. Ichikawa, J. Org. 59. K. Surowiec, T. Fuchigami, Tetrahedron
Chem. 1994, 59, 607–615; (b) S. Furuta, Lett. 1992, 33, 1065–1068.
T. Fuchigami, Electrochim. Acta 1998, 43, 60. K. Surowiec, T. Fuchigami, J. Org. Chem.
3183–3191. 1992, 57, 5781–5783.
34. G. Kaupp, F. Koeleli, E. Gruendken, Angew. 61. T. Fuchigami, A. Konno, K. Nakagawa
Chem. 1985, 24, 864–865. et al., J. Org. Chem. 1994, 59, 5933–5941.
35. J. Yoshida, M. Watanabe, H. Toshioka et al., 62. T. Fuchigami, T. Hayashi, A. Konno, Tetra-
J. Electroanal. Chem. 2001, 507, 55–65. hedron Lett. 1992, 33, 3161–3164.
36. J. Yoshida, S. Isoe, Tetrahedron Lett. 1987, 63. A. Konno, T. Fuchigami, J. Org. Chem.
28, 6621–6624. 1997, 62, 8579–8581.
37. M. Sugawara, K. Mori, J. Yoshida, Elec- 64. T. Fuchigami, S. Narizuka, A. Konno, J.
trochim. Acta. 1997, 42, 1995–2003. Org. Chem. 1992, 57, 3755–3757.
38. T. Shono, Y. Matsumura, K. Inoue, J. Chem. 65. T. Fuchigami, S. Narizuka, A. Konno, et al.,
Soc., Chem. Commun. 1983, 1169–1171. Electrochim. Acta 1998, 43, 1985–1989.
39. K. Irie, K. Aoe, T. Tanaka et al., J. Chem. 66. S. Higashiya, S. Narizuka, A. Konno et al.,
Soc., Chem. Commun. 1985, 633–635. J. Org. Chem. 1999, 64, 133–137.
40. T. Shono, Y. Matsumura, K. Tsubata et al., 67. H. Ishii, N. Yamada, T. Fuchigami, Tetrahe-
J. Org. Chem. 1986, 51, 2590–2592. dron 2001, 57, 9067–9072.
41. G. Kardassis, P. Brungs, C. Nothelfer et al., 68. DE 2855 508, BASF; Chem. Abstr. 1980, 93,
Tetrahedron 1998, 54, 3479–3488. 140061r.
42. A. Papadopoulos, J. Heyer, K.D. Ginzel 69. EP 72914, BASF; Chem. Abstr. 1983, 98,
et al., Chem. Ber. 1989, 122, 2159–2164. 169382k.
43. P.D. Palasz, J.H.P. Utley, J.D. Hardstone, J. 70. T. Shono, T. Okada, T. Furuse et al., Tetra-
Chem. Soc., Perkin Trans. 1984, 2, 807–813. hedron Lett. 1992, 33, 4337–4340.
44. R. Malassene, E. Vanquelef, L. Toupet et al., 71. T. Shono, T. Nozoe, H. Maekawa et al.,
Org. Biomol. Chem. 2003, 1, 547–551. Tetrahedron 1991, 47, 593–603.
45. S. Andreades, E.W. Zahnow, J. Am. Chem. 72. L. Eberson, F. Radner, Acta Chem. Scand.
Soc. 1969, 91, 4181–4190. 1992, 46, 312–314.
46. T. Chiba, Y. Takata, J. Org. Chem. 1977, 42, 73. K. Yoshida, J. Am. Chem. Soc. 1977, 99,
2973–2977. 6111–6113.
47. E. Le Gall, J.-P. Hurvois, S. Sinbandhit, Eur. 74. R.S. Glass, V.V. Jouikov, N.V. Bojkova,
J. Org. Chem. 1999, 2645–2653. Proceedings Electrochemical Society, 2000,
48. A. Konno, T. Fuchigami, Y. Fujita et al., J. (New Directions in Organic Electrochem-
Org. Chem. 1990, 55, 1952–1954. istry), pp. 5–8.
75. I. Nishiguchi, O. Kanbe, K. Itoh et al., Syn- 99. M. Ishifune, H. Yamashita, Y. Kera et al.,
lett 2000, 89–91. Electrochim. Acta 2003, 48, 2405–2409.
76. D.R. Henton, R.A. McCreery, J.S. Swenton, 100. T. Shono, T. Nozoe, Y. Yamaguchi et al.,
J. Org. Chem. 1980, 45, 369–378. Tetrahedron Lett., 1991, 32, 1051–1054.
77. D. Degner, Top. Curr. Chem. 1988, 148, 101. M. Durandetti, C. Meignein, J. Perichon, J.
1–95, there 22–23. Org. Chem. 2003, 68, 3121–3124.
78. H. Baltes, E. Steckhan, H.J. Schaefer, Chem. 102. C. Gosmini, Y. Rollin, J. Perichon et al.,
Ber. 1978, 111, 1294–1314. Tetrahedron, 1997, 53, 6027–6034.
79. S. Torii, K. Uneyama, M. Ono, Tetrahedron 103. D. Franco, E. Dunach, Tetrahedron 2002, 58,
Lett. 1980, 21, 2741–2744. 9289–9296.
80. S. Torii, Electroorganic Synthesis, Part I 104. M. Tokuda, T. Kabuki, Y. Katoh et al., Tetra-
Oxidations, VCh-Kodansha, Tokyo, 1985, hedron Lett. 1995, 36, 3345–3348.
pp. 275–276. 105. M. Kyoda, T. Yokoyama, H. Maekawa et al.,
81. A. Bewick, D.E. Coe, J.M. Mellor, et al., Synlett 2001, 1535–1538.
J. Chem. Soc., Perkin Trans. 1985, 1, 106. N. Kurono, K. Sugita, M. Tokuda, Tetrahe-
1033–1038. dron, 2000, 56, 847–854.
82. T. Shono, Y. Matsumura, O. Onomura 107. E. Chiozza, M. Desigaud, J. Greiner et al.,
et al., J. Org. Chem. 1987, 52, 536–541. Tetrahedron Lett. 1998, 39, 4831–4834.
83. K. Fujimoto, Y. Tokuda, Y. Matsubara et al., 108. S. Derien, E. Dunach, J. Perichon, J. Am.
Tetrahedron Lett. 1995, 36, 7483–7486. Chem. Soc. 1991, 113, 8447–8454.
84. M. Tokuda, H. Fujita, T. Miyamoto et al., 109. S. Derien, J.C. Clinet, E. Dunach et al., J.
Tetrahedron 1993, 49, 2413–2426. Org. Chem. 1993, 58, 2578–2588.
85. T.M. Siegel, L.L. Miller, J.Y. Becker, J. 110. S. Derien, J.C. Clinet, E. Dunach et al.,
Synlett 1990, 361–364.
Chem. Soc., Chem. Commun. 1974, 341–342.
111. T. Shono, M. Mitani, J. Am. Chem. Soc.
86. M. Klehr, H.J. Schäfer, Angew. Chem. 1975,
1971, 93, 5284–5286.
14, 247–248.
112. T. Shono, S. Kashimura, Y. Mori et al., J.
87. S. Torii, T. Okamoto, N. Ueno, J. Chem.
Org. Chem. 1989, 54, 6001–6003.
Soc., Chem. Commun. 1978, 293–294.
113. S. Goda, K. Yamada, Y. Yamamoto et al., J.
88. T. Uchida, Y. Matsubara, I. Nishiguchi
Electroanal. Chem. 2003, 545, 129–140.
et al., J. Org. Chem. 1990, 55, 2938–2943.
114. R. Gorny, H.J. Schäfer, R. Fröhlich, Angew.
89. H.J. Schäfer in Organic Electrochemistry Chem. 1995, 34, 2007–2009.
(Eds.: H. Lund, O. Hammerich), 4th 115. J. Heimann, H.J. Schäfer, R. Fröhlich et al.,
ed., Marcel Dekker, New York, 2001, Eur. J. Org. Chem. 2003, 2919–2932.
pp. 883–968, Chap. 22. 116. R. Munusamy, K. Samban Dhathathreyan,
90. K.D. Moeller, Top. Curr. Chem. 1997, 185, K. Kuppusamy Balasubramanian et al., J.
49–86. Chem. Soc., Perkin Trans. 2001, 2, 1154–1166.
91. J. Yoshida, K. Muraki, H. Funahashi et al., 117. F. Edamura, D. Kyriacou, J. Love, US Patent
J. Org. Chem. 1986, 51, 3996–4000. 4217185, 1980; Chem. Abstr. 1981, 94, 22193.
92. S. Satoh, H. Suginome, H. Tokuda, Bull. 118. D. Kyriacou, unpublished work, Univ. of
Chem. Soc. Jpn. 1983, 56, 1791–1794. Massachusetts, Dept. of Chemistry, Lowell,
93. M. Tokuda, S. Satoh, H. Suginome, J. Org. MA.
Chem., 1989, 54, 5608–5613. 119. T.A. Thornton, G.A. Ross, D. Patil et al., J.
94. S. Satoh, H. Suginome, M. Tokuda, Bull. Am. Chem. Soc. 1989, 111, 2434–2440.
Chem. Soc. Jpn. 1981, 54, 3456–3459. 120. U. Abkulut, L. Toppare, J.H.P. Utley, J.
95. R. Scheffold, M. Dike, S. Dike et al., J. Am. Chem. Soc., Perkin Trans. 1982, 2, 391–394.
Chem. Soc. 1980, 102, 3642–3644. 121. O. Manousek, P. Zuman, Collect. Czech.
96. I. Yamanaka, K. Nakagaki, T. Akimoto Chem. Commun. 1964, 29, 1432–1457.
et al., J. Chem. Soc., Perkin Trans. 1996, 2, 122. L. Horner, A. Mentrup, Liebigs Ann. Chem.
2511–2517. 1961, 646, 49–64.
97. K. Otsuka, K. Furuya, Electrochim. Acta 123. L. Horner, H. Neumann, Chem. Ber. 1965,
1992, 37, 1135–1141. 98, 1715–1721.
98. E. Kariv-Miller, K.E. Swenson, G.K. Lehman 124. B. Lamm, Tetrahedron Lett. 1972, 13,
et al., J. Org. Chem. 1985, 50, 556–560. 1469–1470.
125. J. Simonet, H. Lund, Acta Chem. Scand. 150. W. Schmidt, E. Steckhan, Angew. Chem.
1977, B31, 909–911. 1979, 18, 801–802.
126. F. Beck, Angew. Chem. 1972, 11, 760–781. 151. W. Schmidt, E. Steckhan, Angew. Chem.
127. M.F. Nielsen, J.H.P. Utley in Organic Elec- 1979, 18, 802–803.
trochemistry (Eds.: H. Lund, O. Ham- 152. H. Tanaka, Y. Tokumaru, K. Fukui, et al. in
merich), Marcel Dekker, New York, 2001, Novel Trends in Electroorganic Synthesis (Ed.:
pp. 812–820, Chap. 21. S. Torii), Springer, Tokyo, 1998, pp. 71–72.
128. L. Mandell, R.F. Daley, R.A. Day Jr., J. Org. 153. J. Yoshida, T. Murata, S. Isoe, Tetrahedron
Chem. 1976, 41, 4087–4089. Lett. 1986, 27, 3373–3376.
129. L.A. Powell, R.M. Wightman, J. Am. Chem. 154. J. Yoshida, Y. Ishichi, S. Isoe, J. Am. Chem.
Soc. 1979, 101, 4412–4413. Soc. 1992, 114, 7594–7595.
130. D.N. Sopher, J.H.P. Utley, J. Chem. Soc., 155. J. Yoshida, M. Sugawara, M. Tatsumi et al.,
Perkin Trans. 1984, 2, 1361–1367. J. Org. Chem. 1998, 63, 5950–5961.
131. T. Fuchigami, K. Suzuki, T. Nonaka, Elec- 156. H. Sun, K.D. Moeller, Org. Lett. 2003, 5,
trochim. Acta 1990, 35, 239–244. 3189–3192.
132. T. Fuchigami, A. Konno in Electroorganic 157. K.D. Moeller, P.W. Wang, S. Tarazi et al., J.
Synthesis, Manuel M. Baizer Meml. Symp. Org. Chem. 1991, 56, 1058–1067.
(Eds.: R.D. Little, N.L. Weinberg), Marcel 158. J.M. Chapuzet, A. Lasia, J. Lessard in Elec-
Dekker, New York, 1991, 387–394. trocatalysis (Eds.: J. Lipkowski, P.N. Ross),
133. F. Lichtenthaler, S. Immel, D. Martin et al., Wiley-VCH, New York, 1998, pp. 155–196.
Starch/Staerke 1992, 44, 445–456. 159. L. Coche, J.C. Moutet, J. Am. Chem. Soc.
134. L. Eberson, Electron Transfer Reactions in 1987, 109, 6887–6889.
Organic Chemistry, Springer, Berlin, 1987. 160. S. Maki, Y. Harada, R. Matsui et al., Tetra-
135. A.M. Couper, D. Pletcher, F.C. Walsh, hedron Lett. 2001, 42, 8323–8327.
Chem. Rev. 1990, 90, 837–865, there 856. 161. J.M. Chapuzet, R. Labrecque, M. Lavoie
136. L. Horner, W. Brich, Liebigs Ann. Chem. et al., Can. J. Chim. Phys. Phys.-Chim. Biol.
1977, 1354–1364. 1996, 93, 601–610.
137. Y. Kunugi, T. Nonaka, Y.B. Chong et al., 162. H. Shechter, D.E. Ley, L. Zeldin, J. Am.
Electrochim. Acta 1992, 37, 353–355. Chem. Soc. 1952, 74, 3664–3668.
138. H.J. Schäfer, Top. Curr. Chem. 1990, 152, 163. W.J. Seager, P.J. Elving, J. Am. Chem. Soc.
91–151. 1950, 72, 5183–5185.
139. M.M. Baizer, J. Electrochem. Soc. 1964, 111, 164. A.J. Fry, M.A. Mitnick, R.G. Reed, J. Org.
215–222. Chem. 1970, 35, 1232–1234.
140. E. Steckhan, Top. Curr. Chem. 1987, 142, 165. A. Kunugi, A. Muto, T. Hirai, Bull. Chem.
1–69. Soc. Jpn. 1985, 58, 1262–1266.
141. R.G. Pearson, Chemical Hardness, Wiley- 166. S. Torii, H. Okumoto, H. Tanaka, J. Org.
VCH, Weinheim, 1997. Chem. 1980, 45, 1330–1332.
142. H.J. Schäfer, Top. Curr. Chem. 1987, 142, 167. B. Lamm, K. Ankner, Acta Chem. Scand.
102–129. 1978, B32, 193–196.
143. K. Schnatbaum, H.J. Schäfer, Synthesis 168. S. Wawzonek, J.D. Frederickson, J. Elec-
1999, 864–872. trochem. Soc. 1959, 106, 325–327.
144. M. Schämann, H.J. Schäfer, Eur. J. Org. 169. R.E. Erickson, C.M. Fisher, J. Org. Chem.
Chem. 2003, 351–358. 1970, 35, 1604–1606.
145. T. Inokuchi, S. Matsumoto, S. Torii, J. Org. 170. S. Wieditz, H.J. Schäfer, Acta Chem. Scand.
Chem. 1991, 56, 2416–2421. 1983, B37, 475–483.
146. T. Maki, K. Fukae, H. Harasawa et al., 171. C. van der Stouwe, H.J. Schäfer, Chem. Ber.
Tetrahedron Lett. 1998, 39, 651–654. 1981, 114, 946–958.
147. M. Shibata, N. Furuya, M. Watanabe, J. 172. M.H. Khalifa, A. Rieker, Tetrahedron Lett.
Electroanal. Chem. 1993, 344, 389–393. 1984, 25, 1027–1030.
148. S.M. Weinreb, G.A. Epling, R. Comi et al., 173. M. Ochiai, O. Aki, A. Morimoto et al., J.
J. Org. Chem. 1975, 40, 1356–1358. Chem. Soc., Perkin Trans. 1974, 1, 258–262.
149. W. Schmidt, E. Steckhan, Angew. Chem. 174. T. Fuchigami, Z.E. Kandeel, T. Nonaka,
1978, 17, 673–674. Bull. Chem. Soc. Jpn. 1986, 59, 338–340.
175. J.G. Gourcey, M. Hodler, B. Terem et al., J. 198. R.D. Little, K.D. Moeller, Interface Elec-
Chem. Soc., Chem. Commun. 1976, 779–780. trochem. Soc. 2002 (Winter), 36–42.
176. R.L. Blankespoor, A.N.K. Lau, L.L. Miller, J. 199. K.D. Moeller, Tetrahedron 2000, 56,
Org. Chem. 1984, 49, 4441–4446. 9527–9554.
177. U. Husstedt, H.J. Schäfer, Synthesis 1979, 200. K.D. Moeller, L.V. Tinao, J. Am. Chem. Soc.
964–966. 1992, 114, 1033–1041.
178. M.F. Semmelhack, G.E. Heinsohn, J. Am. 201. D.A. Frey, S.H. Reddy, K.D. Moeller, J. Org.
Chem. Soc. 1972, 94, 5139–5140. Chem. 1999, 64, 2805–2813.
179. J. Engels, Liebigs Ann. Chem. 1980, 557–563. 202. D.A. Frey, N. Wu, K.D. Moeller, Tetrahe-
180. E.L. Eliel, S.H. Wilen, L.N. Mander, Stereo- dron Lett. 1996, 37, 8317–8320.
chemistry of Organic Compounds, Wiley, New 203. Y. Sun, B. Liu, J. Kao et al., Org. Lett. 2001,
York, 1994. 3, 1729–1732.
181. R.E. Gawley, J. Aubé, Principles of Asymmet- 204. D.A. Frey, S.H.K. Reddy, K.D. Moeller, J.
ric Synthesis, Elsevier, Oxford, 1996. Org. Chem. 1999, 64, 2805–2813.
182. R.S. Atkinson, Stereoselective Synthesis, Wi- 205. J. Mihelcic, K.D. Moeller, J. Am. Chem. Soc.
ley, New York, 1995. 2003, 125, 36–37.
183. J. Seyden-Penne, Chiral Auxiliaries and 206. L. Eberson, H. Sternerup, Acta Chem.
Ligands in Asymmetric Synthesis, Wiley, New Scand. 1972, 26, 1431–1442.
York, 1995. 207. H. Sternerup, Acta Chem. Scand. 1974, B28,
184. I. Ojima, (Ed.), Catalytic Asymmetric Synthe- 969–980.
sis, VCH, Weinheim, 1993. 208. L. Kabore, S. Chebli, R. Faure et al., Tetra-
185. E.N. Jacobsen, A. Pfaltz, H. Yamamoto, hedron Lett. 1990, 31, 3137–3140.
(Eds.), Comprehensive Asymmetric Catalysis, 209. M. Thaning, L.G. Wistrand, Acta Chem.
Springer, Berlin, 1999, Vol. 1–3. Scand. 1989, 43, 290–295.
186. L. Eberson, G. Ryde-Petterson, Acta Chem. 210. P.D. Palasz, J.H.P. Utley, J.D. Hardstone, J.
Scand. 1973, 27, 1159–1161. Chem. Soc., Perkin Trans. 1984, 2, 807–813.
187. L. Eberson, K. Nyberg, R. Servin, Acta 211. E. Le Gall, J.P. Hurvois, T. Renaud et al.,
Chem. Scand. 1976, B30, 906–907. Liebigs Ann. Recueil 1997, 2089–2101.
188. G. Hawkes, J.H.P. Utley, G.B. Yates, J. 212. E. Steckhan, P. Brungs, A. Zietlow, et al.
Chem. Soc. 1973, 305–306; J. Chem. Soc., in Modern Methodology of Organic Synthe-
Perkin Trans. 1976, 2, 1709–1716. sis, Proceedings of the 1991 International
189. B. Klotz-Berendes, H.J. Schäfer, Angew. Symposium on Organic Reactions, Kyoto
Chem. 1995, 34, 189–191. (Ed.: S. Shono), Kodansha, Tokyo, 1992,
190. H.J. Schäfer in Radicals in Organic Syn- pp. 323–337.
thesis (Eds.: P. Renaud, M.P. Sibi), Wiley- 213. M. Plehiers, C. Hootele, Can. J. Chem. 1996,
VCH, Weinheim, 2001, pp. 250–297, pp. 74, 2444–2453.
269–270, Vol. 1. 214. D. Baba, Y.-J. Yang, B.-J. Uang et al., J.
191. H.J. Schäfer in Radicals in Organic Synthesis Fluorine Chem. 2003, 121, 93–96.
(Eds.: P. Renaud, M.P. Sibi), Wiley-VCH, 215. H.J. Schäfer, Top. Curr. Chem. 1990, 152,
Weinheim, 2001, 250–297, pp. 273–274, 91–151, there 115–140.
Vol. 1. 216. E. Laurent, M. Thomalla, Bull. Soc. Chim.
192. D.P. Curran, N.A. Porter, B. Giese, Stereo- Fr. 1977, 834–841.
chemistry of Radical Reactions, VCH, Wein- 217. T. Imagawa, S. Sugita, T. Akiyama et al.,
heim, 1996. Tetrahedron Lett. 1981, 22, 2569–2572.
193. M. Huhtasaari, H.J. Schäfer, H. Luftmann, 218. T. Shono, I. Nishiguchi, S. Yamane et al.,
Acta Chem. Scand. Ser. 1983, B37, 537–547. Tetrahedron Lett. 1969, 1965–1968.
194. Y. Matsumura, M. Nishimura, M. Watanabe 219. L.B. Rodewald, M.C. Lewis, Tetrahedron
et al., Electrochim. Acta 1997, 42, 2233–2239. 1971, 27, 5273–5280.
195. N. Kise, T. Ueda, K. Kumada et al., J. Org. 220. D. Seebach, R. Charczuk, Ch. Gerber et al.,
Chem. 2000, 65, 464–468. Helv. Chim. Acta 1989, 72, 401–425.
196. J.M. Bobitt, I. Noguchi, H. Yagi et al., J. Org. 221. P. Renaud, D. Seebach, Helv. Chim. Acta
Chem. 1976, 41, 845–850. 1986, 69, 1704–1710.
197. G. Palmisano, B. Danieli, G. Lesma et al., 222. P. Renaud, D. Seebach, Synthesis 1986,
Helv. Chim. Acta 1992, 75, 813–824. 424–426.
223. Y. Matsumura, G.N. Wanyoike, O. 247. T. Lübbers, Ph.D. thesis, Univ. Muenster
Onumura et al., Electrochim. Acta 2003, 48, (FRG), Muenster, 1991.
2957–2966. 248. A. Matzeit, H.J. Schäfer, C. Amatore, Syn-
224. T. Shono, T. Kosaka, Tetrahedron Lett. 1968, thesis 1995, 1432–1444.
6207–6208. 249. M. Tokuda, T. Miyamoto, H. Fujita et al.,
225. K. Möller, H.J. Schäfer, Electrochim. Acta Tetrahedron 1991, 47, 747–756.
1997, 42, 1971–1978. 250. S. Yamamura, Y. Shizuri, H. Shigemori
226. F.D. Mango, W.A. Bonner, J. Org. Chem. et al., Tetrahedron 1991, 47, 635–644.
1964, 29, 1367–1371. 251. S. Maki, T. Suzuki, S. Kosemura et al.,
227. J. Delaunay, J. Simonet, L. Toupet, J. Chem. Tetrahedron Lett. 1991, 37, 4973–4976.
Soc., Chem. Commun. 1986, 1093–1094. 252. S. Maki, S. Kosemura, S. Yamamura et al.,
228. J.P. Dirlam, L. Eberson, Acta Chem. Scand. Chem. Lett. 1992, 651–654.
1972, 26, 1454–1464. 253. K. Chiba in Novel Trends in Electroorganic
229. B. Liu, K.D. Moeller, Tetrahedron Lett. 2001, Synthesis (Ed.: S. Torii), Springer, Tokyo,
42, 7163–7165. 1998, pp. 25–28.
230. R. Brettle, J.R. Sutton, J. Chem. Soc., Perkin 254. K. Chiba, M. Jinno, R. Kuramoto et al.,
Trans. 1 1975, 1947–1954. Tetrahedron Lett. 1998, 39, 5527–5530.
231. I. Stibor, J. Srogl, M. Janda et al., Col- 255. K. Chiba, M. Jinno, A. Nozaki et al., J.
lect. Czech. Chem. Commun. 1982, 47, Chem. Soc., Chem. Commun. 1997,
3261–3267. 1403–1404.
232. J. Srogl, M. Janda, I. Stibor et al., Col- 256. K. Chiba, J. Sonoyama, M. Tada, J. Chem.
lect. Czech. Chem. Commun. 1978, 43, Soc., Perkin Trans 1996, 1, 1435–1443, there
2015–2023. earlier literature.
233. W. Krumme, Ph.D. thesis, University 257. S. Yamamura in Novel Trends in Electroor-
Münster, Münster, 1999. ganic Synthesis (Ed.: S. Torii), Kodansha,
234. I. Barba, C. Gomez, R. Chinchilla, J. Org. Tokyo, 1995, pp. 265–268.
Chem. 1990, 55, 3272–3273. 258. S. Yamamura in Novel Trends in Electroor-
235. A. Bensadat, E. Laurent, R. Tardivel, Nouv. ganic Synthesis (Ed.: S. Torii), Springer,
J. Chim. 1981, 5, 397–411. Tokyo, 1998, pp. 19–22.
236. E. Laurent, H. Lefranc, R. Tardivel, Nouv. J. 259. S. Yamamura, Y. Shizuri, H. Shikemori
Chim. 1984, 8, 345–348. et al., Tetrahedron 1991, 47, 635–644.
237. E. Laurent, R. Tardivel, H. Benotmane et al., 260. H. Takadura, K. Toyoda, S. Yamamura,
Bull. Soc. Chim. Fr. 1990, 127, 468–475. Tetrahedron Lett., 1996, 37, 4043–4046.
238. A. Klemer, G. Nicolaus, Chem. Ber. 1979, 261. K.D. Moeller, Top. Curr. Chem. 1997, 185,
112, 3063–3071. 49–86, there 66–69 with further literature.
239. N.L. Weinberg, A.K. Hoffman, Can. J. 262. J.D. Anderson, M.M. Baizer, Tetrahedron
Chem. 1971, 49, 740–745. Lett. 1966, 511–514.
240. J.A. Bloom, M. Fleischmann, J.M. Mellor, J. 263. J.D. Anderson, M.M. Baizer, J.P. Petrovich,
Chem. Soc., Perkin Trans. 1986, 1, 79–82. J. Org. Chem. 1966, 31, 3890–3903.
241. A. Bewick, D.E. Coe, J.M. Mellor et al., J. 264. J.H.P. Utley, M. Gullu, M. Motevalli, J.
Chem. Soc., Chem. Commun. 1980, 51–52. Chem. Soc., Perkin Trans. 1995, 1,
242. A. Bewick, D.E. Coe, J.M. Mellor et al., 1961–1970.
J. Chem. Soc., Perkin Trans. 1985, 1, 265. I. Fussing, M. Gullu, O. Hammerich et al.,
1033–1038. J. Chem. Soc., Perkin Trans. 1996, 2,
243. S. Torii, K. Uneyama, M. Ono, Tetrahedron 649–658.
Lett. 1980, 21, 2741–2744. 266. I. Fussing, O. Hammerich, A. Hussain
244. F.M. Ventalon, R. Faure, E.G. Laurent et al., Acta Chem. Scand. 1998, 52, 328–337.
et al., Tetrahedron : Asymmetry 1994, 5, 267. N. Kise, K. Iwasaki, N. Tokieda et al., Org.
1909–1912. Lett. 2001, 3, 3241–3244.
245. Y.N. Ogibin, G.I. Nikishin, Russ. Chem. Rev. 268. N. Kise, S. Iitaka, K. Iwasaki et al., J. Org.
2001, 70, 543–576. Chem. 2002, 67, 8305–8315.
246. J. Weiguny, H.J. Schäfer, Liebigs Ann. 269. N. Kise, Y. Hirata, T. Hamaguchi et al.,
Chem. 1994, 225, 235–242. Tetrahedron Lett. 1999, 40, 8125–8128.
270. N. Kise, S.-I. Mashiba, N. Ueda, J. Org. 292. D.F. Tomkins, J.H. Wagenknecht, J. Elec-
Chem. 1998, 63, 7931–7938. trochem. Soc. 1978, 125, 372–375.
271. J.H.P. Utley, C.Z. Smith, M. Motevalli, J. 293. M.D. Birkett, A.T. Kuhn, Electrochim. Acta
Chem. Soc., Perkin Trans. 2000, 2, 1980, 25, 273–278.
1053–1057. 294. V.P. Gul’tyai, L.M. Korotaeva, Izv. Akad.
272. H.P. Utley, M. Gullu, C. De Matteis et al., Nauk, SSSR, Ser. Khim. 1982, 165–170;
Tetrahedron 1995, 51, 11873–11882. Chem. Abstr. 1982, 96, 141941b.
273. J. Delaunay, A. Orliac, J. Simonet, J. Elec- 295. L. Mattiello, L. Rampazzo, Electrochim. Acta
trochem. Soc. 1995, 142, 3613–3619. 1997, 42, 2257–2264.
274. J. Delaunay, A. Lebouc, G. Le Guillanton 296. E. Kariv-Miller, T.J. Mahachi, J. Org. Chem.
et al., Electrochim. Acta 1982, 27, 287–291. 1986, 51, 1041–1045.
275. J. Andersson, L. Eberson, J. Chem. 297. E. Kariv-Miller, R.I. Pacut, G.K. Lehmann,
Soc., Chem. Commun. 1976, 565–566; Top. Curr. Chem. 1988, 148, 97–130.
J. Andersson, L. Eberson, C. Svensson, Acta 298. R. Andreu, D. Pletcher, Electrochim. Acta
Chem. Scand. 1978, B32, 234. 2003, 48, 1065–1071.
276. B. Terem, J.H.P. Utley, Electrochim. Acta 299. J.D. Parrish, R.D. Little, Book of Abstracts,
1979, 24, 1081–1084. 219th ACS National Meeting, San Fran-
277. F. Fournier, J. Berthelot, J.-J. Basselier, cisco, 26–30 March 2000.
Tetrahedron 1985, 41, 5667–5676; F. 300. M. Atobe, T. Tonoi, T. Nonaka, Electrochem.
Fournier, D. Davoust, J.-J. Basselier, Tetra- Commun. 1999, 1, 593–596.
hedron 1985, 41, 5677–5683. 301. J.F. Rusling, P. Zuman, J. Org. Chem. 1981,
278. J.D. Anderson, M.M. Baizer, Tetrahedron 46, 1906–1909.
Lett. 1966, 511–515. 302. L. Mattiello, L. Rampazzo, J. Chem. Soc.,
Perkin Trans. 1993, 2, 2243–2247.
279. L. Moens, M.M. Baizer, R.D. Little, J. Org.
303. A.K. Yadav, A. Singh, Synlett 2000,
Chem. 1986, 51, 4497–4498.
1199–1201.
280. R.D. Little, M.K. Schwaebe, Top. Curr.
304. L. Horner, D.H. Skaletz, Liebigs Ann. Chem.
Chem. 1997, 185, 1–48.
1975, 1210–1228.
281. R.D. Little, M.K. Schwaebe, Top. Curr.
305. B. Czochralska, D. Shugar, S.K. Arora et al.,
Chem. 1997, 185, 12–13.
J. Am. Chem. Soc. 1977, 99, 2583–2588.
282. S. Kratschmer, H.J. Schäfer, R. Fröhlich, J.
306. T. Shono, N. Kise, E. Shirakawa et al., J.
Electroanal. Chem. 2001, 507, 2–10. Org. Chem. 1991, 56, 3063–3067.
283. J.H. Stocker, R.M. Jenevein, J. Org. 307. T. Siu, W. Li, A.K. Yudin, J. Comb. Chem.
Chem. 1968, 33, 294–297; J.H. Stocker, 2001, 3, 554–558.
R.M. Jenevein, J. Org. Chem. 1968, 33, 308. T. Shono, N. Kise, T. Fujimoto et al., J. Org.
2145–2146. Chem. 1994, 59, 1730–1740.
284. V.J. Puglisi, G.L. Clapper, D.H. Evans, Anal. 309. T. Shono, Y. Morishima, N. Moriyoshi
Chem. 1969, 41, 279–282. et al., J. Org. Chem. 1994, 59, 273–275.
285. A. Bewick, H.P. Cleghorn, J. Chem. Soc., 310. R.N. Gourley, J. Grimshaw, J. Chem. Soc.
Perkin Trans. 1973, 2, 1410–1413; (C) 1968, 2388–2393.
A. Bewick, D.J. Brown, J. Chem. Soc., Perkin 311. F. Ammar, C.P. Andrieux, J.M. Saveant, J.
Trans. 1977, 2, 99–102. Electroanal. Chem. 1974, 53, 407–416.
286. S. Wawzonek, A. Gundersen, J. Electrochem. 312. T. Nonaka, A. Udagawa, K. Odo, Chem. Lett.
Soc. 1964, 111, 324–328. 1975, 1261–1266.
287. J. Grimshaw, J.S. Ramsey, J. Chem. Soc. (C) 313. J. Armand, L. Boulares, Can. J. Chem. 1976,
1966, 653–655. 54, 1197–1204.
288. J.H. Stocker, R.M. Jenevein, J. Org. Chem. 314. T. Nonaka, M. Asai, Bull. Chem. Soc. Jpn.
1968, 33, 2145–2146. 1978, 51, 2976–2982.
289. A.D. Thomsen, H. Lund, Acta Chem. Scand. 315. T. Shono, N. Kise, T. Fujimoto et al., J. Org.
1969, 23, 3582. Chem. 1992, 57, 7175–7187.
290. J.H. Stocker, R.J. Jenevein, J. Org. Chem. 316. S. Goda, K. Yamada, Y. Yamamoto et al., J.
1969, 34, 2807–2810. Electroanal. Chem. 2003, 545, 129–140.
291. J.H. Stocker, R.M. Jenevein, D.H. Kern, J. 317. T. Shono, N. Kise, T. Suzumoto et al., J.
Org. Chem. 1969, 34, 2810–2813. Am. Chem. Soc. 1986, 108, 4676–4677.
318. N. Kise, T. Suzumoto, T. Shono, J. Org. 342. T. Nonaka, M. Takahashi, T. Fuchigami,

Chem. 1994, 59, 1407–1413. Denki Kagaku 1983, 51, 129–130; Chem.
319. S. Condon-Gueugnot, D. Dupre, J.Y. Ned- Abstr. 1983, 98, 187917t.
elec et al., Synthesis 1997, 1457–1460. 343. P. Kabasakalian, J. McGlotten, A. Basch,
320. M. Benedetto, G. Miglierini, P.R. Mussini M.D. Yudis, J. Org. Chem 1961, 26,
et al., Carbohydr. Lett. 1995, 1, 321–328. 1738–1744.
321. J. Sarrazin, A. Tallec, Tetrahedron Lett., 344. E.L. Shapiro, M.J. Gentles, J. Org. Chem.
1977, 1579–1582. 1981, 46, 5017–5019.
322. C.I.D. Matteis, J.H.P. Utley, J. Chem. Soc., 345. A.V. Kamernitskii, I.G. Reshetova, E.I.
Perkin Trans. 1992, 2, 879–883. Chernoburnova et al., Izv. Akad. Nauk
323. J.B. Lee, P. Cashmore, Chem. Ind. 1966, SSSR, Ser. Khim. (Engl. Ed.) 1984,
1758–1759. 1736–1738; Chem. Abstr. 1985, 102, 62512b.
324. J. Kato, M. Sakuma, T. Yamada, Denki Ka- 346. C. Zielinski, H.J. Schäfer, Tetrahedron Lett.
gaku 1957, 25, 331–337; Chem. Abstr. 1958, 1994, 35, 5621–5624.
52, 4469a. 347. C. Reufer, C. Zielinski, H.J. Schäfer et al.,
325. T. Nonaka, M. Takahashi, T. Fuchigami, Acta Chem. Scand. 1999, 53, 1023–1037.
Bull. Chem. Soc. Jpn. 1983, 56, 2584–2588. 348. A.J. Fry, J.H. Newberg, J. Am. Chem. Soc.
326. L. Horner, H. Röder, Liebigs Ann. Chem. 1967, 89, 24, 6374.
1969, 723, 11–26. 349. A.J. Fry, R.G. Reed, J. Am. Chem. Soc. 1969,
327. R.A. Benkeser, C.A. Tincher, J. Org. Chem. 91, 6448–6451.
1968, 33, 2727–2730. 350. V. Concialini, S. Roffia, D. Savoia, Gazz.
328. K. Junghans, Chem. Ber. 1974, 107, Chim. Ital. 1995, 125, 77–81.
3191–3198. 351. L. Horner, R.J. Singer, Chem. Ber. 1968,
329. K. Junghans, Chem. Ber. 1976, 109, 101, 3329–3331.
395–402. 352. L. Horner, H. Fuchs, Tetrahedron Lett. 1962,
330. L.L. Miller, L. Christensen, J. Org. Chem. 203–204.
1978, 43, 2059–2061. 353. L. Horner, H. Fuchs, Tetrahedron Lett. 1963,
331. B. Koop, H.J. Schäfer, A. Straub, Proceed- 1573–1575.
ings – Electrochemical Society, 2000 (New 354. L. Horner, H. Fuchs, H. Winkler et al.,
Directions in Organic Electrochemistry), Tetrahedron Lett. 1963, 965–967.
pp. 124–127. 355. R. Hazard, S. Jaouannet, A. Tallec, Elec-
332. L. Mandell, R.M. Powers, R.A. Day Jr., J. trochim. Acta 1983, 28, 1095–1104.
Am. Chem. Soc. 1958, 80, 5284–5285. 356. A.J. Fry, R.H. Moore, J. Org. Chem. 1968,
333. T. Nonaka, Y. Kusayanagi, T. Fuchigami, 33, 1283–1284.
Electrochim. Acta 1980, 25, 1679–1680. 357. R.E. Erickson, R. Annino, M.D. Scanlon
334. T. Nonaka, Y. Kusayanagi, Electrochim. Acta et al., J. Am. Chem. Soc. 1969, 91,
1981, 26, 893–898. 1767–1770.
335. T. Nonaka, M. Takahashi, T. Fuchigami, 358. A.J. Fry, J. Touster, Electrochim. Acta 1997,
Bull. Chem. Soc. Jpn. 1983, 56, 158–168 42, 2057–2063.
and 2584–2588. 359. R. Hazard, S. Jaouannet, E. Raoult et al.,
336. T. Nonaka, S. Wachi, T. Fuchigami, Chem. Nouv. J. Chim., 1982, 6, 325–333.
Lett. 1977, 47–50. 360. P.E. Iversen, J.O. Madsen, Tetrahedron 1974,
337. J.P. Coleman, R.J. Kobylecki, J.H.P. Utley, 30, 3477–3480.
J. Chem. Soc., Chem. Commun. 1971, 361. H. Lund, E. Hobolth, Acta Chem. Scand.
104–105. 1976, B30, 895–898.
338. T. Shono, M. Mitani, Tetrahedron 1972, 28, 362. P.J. Elving, I. Rosenthal, A.J. Martin, J. Am.
4747–4750. Chem. Soc. 1955, 77, 5218–5224.
339. J.P. Coleman, R.J. Holman, J.H.P. Utley, J. 363. O.R. Brown, P.H. Middleton, T.L. Threlfall,
Chem. Soc., Perkin Trans. 1976, 2, 879–884. J. Chem. Soc., Perkin Trans 1984, 2, 955–963.
340. R.J. Holman, J.H.P. Utley, J. Chem. Soc., 364. U. Husstedt, H.J. Schäfer, Tetrahedron Lett.
Perkin Trans. 1976, 2, 884–888. 1981, 22, 623–624.
341. G. Le Guillanton, Tetrahedron Lett. 1978, 365. D.W. Sopher, J.H.P. Utley, J. Chem. Soc.,
2567–2570. Chem. Commun. 1981, 134–136.
366. T. Osa, Y. Kashiwagi, Y. Yanagisawa et al., 384. M. Jubault, E. Raoult, J. Chem. Soc., Chem.
J. Chem. Soc., Chem. Commun. 1994, Commun. 1977, 250–251.
2535–2537. 385. M. Jubault, A. Lebouc, A. Tallec, Elec-
367. H. Maekawa, K. Itoh, S. Goda et al., Chiral- trochim. Acta 1982, 27, 1339–1341.
ity 2003, 15, 95–100. 386. L. Horner, D.H. Skaletz, Liebigs Ann. Chem.
368. M. Kuroboshi, H. Yoshihisa, M.N. Cortona 1977, 1365–1409.
et al., Tetrahedron Lett. 2000, 41, 8131–8135. 387. L. Horner, D. Degner, Electrochim. Acta
369. Y. Kashiwagi, K. Uchigama, F. Kurashima 1974, 19, 611–627.
et al., Chem. Pharm. Bull. 1999, 47, 388. R.N. Gourley, J. Grimshaw, P.G. Millar, J.
1051–1052. Chem. Soc. C. 1970, 2318–2323.
370. H. Tanaka, Y. Kawakami, K. Goto et al., 389. U. Hoeweler, N. Schoo, H.J. Schäfer, Liebigs
Tetrahedron Lett. 2001, 42, 445–448. Ann. Chem. 1993, 609–614.
371. T. Komori, T. Nonaka, Chem. Lett. 1984, 390. M.F. Nielsen, B. Batanero, T. Löhl et al.,
509–512. Eur. J. Chem. 1997, 3, 2011–2024.
372. Y. Kashiwagi, Y. Yanagisawa, F. Kurashima 391. T. Küpper, H.J. Schäfer, GDCh-
et al., J. Chem. Soc., Chem. Commun. 1996, Monographie, 21 (Elektrochemische Ver-
2745–2746. fahren fuer Neue Technologien) 2000,
373. E.M. Belgsir, H.J. Schäfer, Chem. Commun. pp. 221–229.
1999, 435–436. 392. H. Simon, H. Guenther, J. Bader et al.,
374. T. Komori, T. Nonaka, J. Am. Chem. Soc. Angew. Chem. 1981, 20, 861–864.
1984, 106, 2656–2659. 393. H. Simon, J. Bader, H. Guenther et al.,
375. T. Komori, T. Nonaka, J. Am. Chem. Soc. Angew. Chem. 1985, 24, 539–553.
1983, 105, 5690–5691. 394. R. Yuan, S. Watanabe, S. Kuwabata et al., J.
376. T. Nonaka, Hyomen 1987, 25, 283–298. Org. Chem. 1997, 62, 2494–2499.
377. B.E. Firth, L.L. Miller, M. Mitani et al., J. 395. N. Takano, K. Matsuda, M. Itaya, Denki
Am. Chem Soc. 1976, 98, 8271–8272. Kagaku 1998, 66, 86–91; Chem. Abstr. 1998,
378. J. Kopilov, E. Kariv, L.L. Miller, J. Am. 128, 167159g.
Chem. Soc. 1977, 99, 3450–3454. 396. E. Steckhan in Organic Electrochemistry
379. M. Jubault, E. Raoult, D. Peltier, Elec- (Eds.: H. Lund, O. Hammerich), Marcel
trochim. Acta 1980, 25, 1359–1367. Dekker, New York, 2001, 1103–1146,
380. M. Jubault, J. Chem. Soc., Chem. Commun. Chap. 27.
1980, 953–954. 397. R. Hazard, S. Jaouannet, A. Tallec, Tetrahe-
381. M. Jubault, E. Raoult, D. Peltier, Elec- dron Lett. 1979, 1105–1108.
trochim. Acta 1981, 26, 287–290. 398. A. Tallec, R. Hazard, A. Le Bouc et al., J.
382. M. Schwientek, S. Pleus, C.H. Hamann, J. Chem. Res. (S) 1986, 342–343.
Electroanal. Chem. 1999, 461, 94–101. 399. R. Hazard, S. Jaouannet, A. Tallec, Tetrahe-
383. A.K. Yadav, A. Singh, Bull. Chem. Soc. Jpn dron 1982, 38, 93–102.
2002, 75, 587–588.
451
14
Electrogenerated Acids and
Bases
Merete Folmer Nielsen

University of Copenhagen, Copenhagen, Denmark
14.1 Electrogenerated Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453

14.1.1 General Concepts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453
14.1.2 Influence of the Solvent-electrolyte System . . . . . . . . . . . . . . . . . . 454
14.1.3 In situ Versus Ex situ Formation of the EGA . . . . . . . . . . . . . . . . 454
14.1.4 Comparison of EGAs with Conventional Acids . . . . . . . . . . . . . . . 455
14.2 Charge-consuming Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . 455

14.2.1 EGA Catalyzed Follow-up Reaction of the Product of Anodic Oxidation 455
14.2.2 EGA Induced Conversion of Substrate . . . . . . . . . . . . . . . . . . . . . 457
14.3 Acid Catalyzed Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458

14.3.1 Ring Opening of Epoxides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
14.3.2 Reaction of Acetals, Ketones, and Aldehydes with Nucleophiles . . . . 460
14.3.3 1,4-Addition to Enones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463
14.3.4 Functional Group Protection . . . . . . . . . . . . . . . . . . . . . . . . . . . 463
14.3.5 Electrophilic Aromatic Substitution . . . . . . . . . . . . . . . . . . . . . . 464
14.3.6 Cyclizations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 464
14.3.7 Diels–Alder Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465
14.4 Electrogenerated Bases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465

14.4.1 General Concepts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465
14.4.2 In situ Versus Ex situ Formation of the EGB . . . . . . . . . . . . . . . . 466
14.4.3 Kinetic Versus Thermodynamic Basicity . . . . . . . . . . . . . . . . . . . 466
14.4.4 Efficiency of the Proton Transfer Reaction . . . . . . . . . . . . . . . . . . 467
14.4.5 Comparison of EGBs with Conventional Bases . . . . . . . . . . . . . . . 468
14.5 Nitrogen Bases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 468

14.5.1 Azo Compounds and Nitrogen Heteroaromatics as Probases . . . . . . 468
14.5.2 Amides as Probases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 468
452 14 Electrogenerated Acids and Bases
14.6 Oxygen Bases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 470

14.6.1 Dioxygen as Probase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 470
14.6.2 Phenols as Probases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 470
14.6.3 Carbonyl Compounds as Probases . . . . . . . . . . . . . . . . . . . . . . . 470
14.7 Carbon Bases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471

14.7.1 Activated Alkenes as Probases . . . . . . . . . . . . . . . . . . . . . . . . . . 471
14.7.2 Carbanions as EGBs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471
14.7.3 Other Electrogenerated Carbon Bases . . . . . . . . . . . . . . . . . . . . . 472
14.8 Reactions Consuming Stoichiometric Amounts of Base . . . . . . . . . 472

14.8.1 Wittig Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472
14.8.2 Addition to Aldehydes and Ketones . . . . . . . . . . . . . . . . . . . . . . . 474
14.8.3 Alkylation of Activated Methylene Compounds . . . . . . . . . . . . . . . 474
14.8.4 Cyanomethylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 476
14.8.5 Carboxylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
14.8.6 Cyclizations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478
14.8.7 Oxidative Conversions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478
14.8.8 Condensations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 480
14.8.9 Miscellaneous Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 480
14.9 Base-Catalyzed Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481

14.9.1 Michael Additions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481
14.9.2 Reactions Involving Aldehydes and Ketones . . . . . . . . . . . . . . . . . 483
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485
453
It is well known that when electrolysis process. Reactions induced by protons

is carried out in a divided cell, the acid- formed directly in an anodic process are
ity of the anolyte and the basicity of the almost exclusively catalytic. The reactions
catholyte increase unless special precau- do not involve oxidation of the substrates
tion is taken. These medium changes and only a catalytic amount of the EGA
may induce acid–base reactions of sub- is required.
strates and/or products leading to un- Protons, generated indirectly by depro-
intended final products or mixtures of tonation of an intermediate during an-
products. However, electrochemical for- odic oxidation of an organic substrate,
mation of strongly acidic or basic species are obviously produced in stoichiomet-
may also be used deliberately as al- ric amounts. Reactions induced by these
ternatives to conventional strong acids protons are typically acid-catalyzed con-
or bases. The use of electrogenerated versions of the initial oxidation product
bases (EGBs) has been particularly ex- or proton-induced reactions/deactivation
plored, and a range of well-defined EGBs of unconverted substrate.
with different basicities have been devel- Direct formation of protons by anodic
oped and used synthetically. In compar- oxidation of dihydrogen, H2 , on acti-
ison, the use of electrogenerated acids vated Pt anodes allows the formation
(EGAs) has received less attention. Both of well-defined quantities of acid [4, 5].
subjects – electrogenerated acid (EGA) [1], However, this method of proton genera-
electrogenerated base (EGB) [2, 3] – have tion has not been used in typical EGA-
previously been reviewed. induced reactions.
In the absence of more easily oxi-
dized substrates, residual water in aprotic
14.1 solvents will undergo oxidation at plat-
Electrogenerated Acids inum anodes. However, the mechanism
of proton formation is not necessar-
14.1.1 ily by simple water oxidation with the
General Concepts evolution of O2 but may involve rad-
ical reactions of the solvent or oxida-
Electrogenerated acids (EGAs) are strong tion of supporting electrolyte anions [6,
Brønsted acids arising from protons pro- 7]. The protons produced, together with
duced directly or indirectly in an anodic the most basic species in solution, form
the EGA. Proton activity can be mea- reduction of the metal cation [1, 8, 12].
sured by indicators such as nitroani- Tetraalkylammonium cations, on the other
lines [8]. hand, may, in aprotic solvents, give rise to
the formation of amines upon reduction,
14.1.2 and the solution becomes buffered. In an
Influence of the Solvent-electrolyte System undivided cell, the difference in proton
activity of an electrolyzed MeCN solution
The successful formation of protons by containing NaClO4 and of one containing
anodic oxidation obviously requires the ab- Bu4 NBF4 was found to be of almost
sence of a supporting electrolyte with easily two orders of magnitude after passage
oxidized anions. Anions such as PF6 − , of the same amount of charge, the
BF4 − , and ClO4 − fulfill the requirement, MeCN-NaClO4 solution being the more
whereas, for example, halide anions and acidic [8]. This was taken as evidence
CH3 COO− normally prevent production for the buffering effect offered by the
of the EGA. Bu4 N+ ion, since independently prepared
The ability of the supporting electrolyte standard solutions of HClO4 and HBF4 in
anion to stabilize the intermediate carbo- MeCN showed similar proton activity [8].
cations in only moderately polar solvents The choice of solvent plays a role for
such as CH2 Cl2 or THF may play an im- (1) the proton activity of the medium and
portant role for product formation. The (2) the involvement of solvent molecules
ClO4 − ion is known to stabilize car- in the follow-up reaction of the inter-
bocations in ether [9] and in alcoholic mediate carbocations. Most EGA-catalyzed
solutions [10], whereas the tosylate anion reactions are carried out in fairly unpolar
(TsO− ) has been suggested to add to reac- solvents such as CH2 Cl2 , ClCH2 CH2 Cl,
tive carbocations [11] (see Sect. 14.3.1). It is THF or mixtures of these. Catalytic reac-
unfortunate that in many cases ClO4 − has tions that involve trapping of a carbocation
proven to be superior in EGA-catalyzed re- intermediate by solvent are typically car-
actions, since the known safety risks of ried out in acetone, MeCN, or MeOH. In
organic perchlorates (explosive) prevent protic solvents such as MeOH, the bulk
the general use of metal perchlorates as solution does not become acidic in undi-
the supporting electrolyte. vided cells, since base (MeO− ) is produced
The significance of the supporting at the cathode. However, in the vicinity of
electrolyte cation depends crucially on the anode the acidity may be sufficiently
whether a divided or an undivided cell high for ketones to undergo acid catalyzed
is used. In a divided cell, the choice of hemiacetal formation [13], see Sect. 14.2.2.
cation is of minor importance but in Where the EGA is formed via elimination
an undivided cell the cathode process of protons during the oxidative conversion
should not lead to formation of base of an organic substrate, the more polar
and thereby to buffering of the solution. MeCN is normally used.
Metal cations such as Li+ , Na+ or Mg2+
are often the choice since in aprotic 14.1.3
solvents the metal cation may be the In situ Versus Ex situ Formation of the EGA
most easily reduced component. This has
been observed as deposits of metal on For acid catalyzed reactions, formation of
the surface of the cathode arising from the EGA ex situ by electrolysis of the
14.2 Charge-consuming Reactions 455
solvent-electrolyte system in the absence 14.2

of a substrate (typically in a divided cell) Charge-consuming Reactions
is commonplace. After electrolysis, sam-
14.2.1
ples of the anolyte may be added to a
EGA Catalyzed Follow-up Reaction of the
solution of the substrate, and the reaction
Product of Anodic Oxidation
carried out as a conventional reaction in
a homogeneous solution. One advantage
One of the first notions of EGA-catalyzed
of an ex situ operation is that substrates, reactions was the rationalization [8, 14]
which may undergo direct anodic oxida- of the unexpected outcome of anodic
tion, can be subject to an EGA-catalyzed oxidation of methyl arenes, (1), in MeCN
conversion without interference from sub- containing various amounts of water.
strate oxidation. The ex situ formation of Preferentially N -benzyl acetamides, (3),
EGA has also been crucial as evidence rather than the benzyl alcohols, (2), were
for the EGA catalysis of a given sub- formed [15, 16] (with increasing amounts
strate conversion as opposed to a chain of water, increasing amounts of aldehyde
mechanism involving radical cations of was formed as a side product [16]). Since
the substrate. In situ formation of the water is a more powerful nucleophile than
EGA obviously takes place in reactions MeCN, it is reasonable to believe that
involving oxidative conversion of the sub- the carbocation formed by overall two-
strate but is also used for purely EGA- electron oxidation and deprotonation is
catalyzed reactions. initially trapped by water. However, the
process is reversible in the presence of a
14.1.4 strong EGA (protons liberated from the
Comparison of EGAs with oxidized substrate), and the carbocation is
Conventional Acids eventually trapped by the excess MeCN,
Scheme 1.
The major advantages of EGAs compared It was demonstrated that in the acidic
to conventional acids relate to their ap- conditions prevailing after electrolysis,
plication in catalytic reactions, Sect. 14.3; benzyl alcohol added to the anolyte was
strongly acidic conditions are obtained quickly converted to the acetamide [8]. The
in the vicinity of the anode although more methyl substituents there were in
the bulk solution is kept essentially neu- the benzene ring, the more stable the
tral. The successful replacement of of- carbocation intermediate became and the
ten expensive and/or moisture-sensitive higher the ratio (3) : (2).
Lewis acids with an EGA is a promis- Similarly, anodic oxidation of bibenzyl
ing strategy, especially because stoichio- ether in wet MeCN leads to benzaldehyde
metric amounts of Lewis acids may, and (3) rather than to benzaldehyde and
in some cases, be substituted with cat- (2), since (2) in this case also undergoes
alytic amounts of the EGA. Similarly, EGA-catalyzed reaction with MeCN [14].
the use of an EGA offers an attrac- Transformation of amines to aldehydes
tive alternative to anhydrous HClO4 that or ketones can be carried out via the anodic
may be difficult to prepare in small α-methoxylation of the corresponding
amounts without being contaminated carbamates, (4), followed by an acid-
with HCl. catalyzed conversion of the α-methoxylated
(%2) (%3)
CH2 OH
Me 10 62
Kinetic 1,2-Me2 5 82
product 1,3-Me2 8 68
H2O
(CH3)n 1,4-Me2 4 71
CH3 CH2 −H+ (2) 1,2,4,5-Me4 0 68
Me6 0 100
−2e−, −H+
EGA
(CH3)n MeCN O
(CH3)n
(1)
CH2 NC CH3 CH2 NH C CH3
MeCN, 0.1 M H2O,
NaClO4, undiv. cell H2O
Thermodynamic
−H+ product
(CH3)n (CH3)n
(3)
Scheme 1 EGA catalysis in side-chain oxidation of methyl arenes.
carbamates into the dimethyl acetals, (5), solvolysis, Scheme 3 [18]. The EGA-
Scheme 2 [17]. When R = H, the anodic catalyzed reaction could not be suppressed
oxidation of (4) leads directly to (5). by the addition of a base. The more strained
Oxidation of N ,N -dialkylamides in ring system, N -acetylaziridine, does not
MeOH normally gives α-methoxylated undergo methoxylation, but only EGA-
amides in high yields. The reaction catalyzed solvolysis (0.5 F), Scheme 4 [18].
also works well for N -formyl-2,2- Oxidation of a 5,8-dihydro-1,4-naphtha-
dimethylazetidine, (6a), but in the lenediol derivative, (7), leads in a 2 F
absence of the methyl groups, (6b), the process to the dihydronaphthoquinone,
primary product undergoes EGA-catalyzed (8), but in a divided cell EGA-catalyzed
OMe R OMe
R MeOH, Et4NOTs
R
EGA
NHCO2Me NHCO2Me 69–78%
Undiv. cell R′ ≠ H R′ OMe
R′ R′
(4) (5)
R = alkyl, R′ = H, alkyl
Scheme 2 EGA-catalyzed conversion of α-methoxy carbamates into acetals.
CHO CHO
MeO OMe
N MeOH, Bu4NBF4 N R=H
R + 2H+
Undiv. cell, 2.1 F R O NH OMe
R R
(6a) R = Me
(6b) R = H
Scheme 3 EGA-catalyzed methanolysis of N-formyl-α-methoxyazetidine.

14.2 Charge-consuming Reactions 457
COMe
MeOH, Bu4NBF4 NH
N OMe
Undiv. cell, 0.5 F
O
Scheme 4 EGA-catalyzed methanolysis of N-acetylaziridine.
conversion to the hydroquinone, (9), In MeOH-Et4 NOTs, oxidation (4 F) of

takes place, and (9) is then further (7) leads exclusively to (8). Subsequent
oxidized (2 F) to the naphthoquinone, oxidation of (8) in MeCN-LiClO4 leads to
(10), Scheme 5 [19]. The EGA is formed (10) in 90% yield (3.5 F) [19].
during the initial oxidation of (7) by loss
of protons, which are not neutralized 14.2.2
in the divided cell. Using 7.5 to 9 F, EGA Induced Conversion of Substrate
good chemical yields (>90%) of (10)
are obtained in MeCN, AcOH or AcOEt Oxidative cleavage of α-hydroxycycloalkan-
containing 10% t-BuOH with LiClO4 , ones, (11), in MeOH-LiClO4 at a Pt
Bu4 NClO4 or LiBF4 as the supporting anode in a divided cell, [13, 20] has been
electrolyte. The presence of an alcohol suggested to take place via the hemiacetal,
(t-BuOH) seems necessary in order to (12), formed in situ by EGA catalysis [13],
prevent formation of oligomeric material. Scheme 6.
OH O OH O
+
−2e , −2H+ EGA −2e , −2H
OH O OH O
(7) (8) (9) (10)
Vitamin K3
Scheme 5 EGA-catalyzed double bond migration.
R1 R1
HO R1
MeOH HO −2e−, −2H+
(CH2)n (CH2)n O (CH2)n 65–95%
EGA MeO
O
OH MeOOC R2
R2 R2
(11) (12)
n = 1, 2 −2e−, −2H+
R1, R2 = alkyl or H
R1 R1 R1
−2e−, −2H+, MeOH MeO MeOH MeO
(CH2)n (CH2)n
(CH2)n EGA
AcO MeO
O OH
R2 R2
R2
(13)
Scheme 6 EGA-catalyzed hemiacetal formation.

The reaction requires 4 to 5 F, and in MeCN/CH2 Cl2 [25] and during the an-
parallel, direct oxidation of (11) cannot odic dimerization/oligomerization of sub-
be excluded. α-Acetoxycycloalkanones un- stituted pyrroles in MeCN [26]. The un-
dergo similar cleavage reactions in MeOH- desired deactivation of the substrate may
LiClO4 . Bond cleavage does not occur for be avoided by addition of base (compet-
(11) in MeOH-Et4 NOTs [13], that is, con- ing reaction of the base as nucleophile is
ditions in which less EGA production is possible) or by using an undivided cell
expected (cf. Sect. 14.1.2), whereas cleav- (competing reduction of substrate or prod-
age of 1,2-diols does take place [21]. uct is possible).
Similarly, oxidation of cycloalkanone
enol acetates, (13), in MeOH/AcOH(10 : 1)-
LiClO4 at a Pt anode in a divided cell 14.3
leads to oxidative cleavage to the (same) Acid Catalyzed Reactions
oxoalkanoates as the corresponding (11),
Scheme 6, [13]. In this case, EGA-catalyzed A number of reactions that are traditionally
conversion into a hemiacetal has also been carried out using either Brønsted or Lewis
suggested, Scheme 6, [13]. Using AcOH- acids as catalysts have been shown to take
Et4 NOTs in an undivided cell (13) gives place in the presence of EGA formed either
a mixture of α,β-cycloalkenones and α- in situ or ex situ. The reactions do not
acetoxycycloalkanones [22, 23]. involve charge-consuming conversions of
Unintended EGA-catalyzed rearrange- the substrates.
ment of substrates during anodic oxidation
14.3.1
has been reported in a number of cases,
Ring Opening of Epoxides
for example, rearrangement of strained
polycyclic hydrocarbons upon oxidation in EGA-catalyzed ring opening of epoxides,
MeCN-LiClO4 [24]. (14), is one of the most-studied catalytic
Unintended deactivation of substrates EGA reactions. The proper choice of
during proton-producing anodic processes solvent and supporting electrolyte allows
such as couplings or substitutions is com- selective formation of a ketone, an allylic
mon. For coupling reactions carried out alcohol, an acetonide, or an α-hydroxy
in polar aprotic solvents, electron-rich sub- ether, Scheme 7.
strates (typically N -, O- or S-compounds) Nonnucleophilic solvents such as
may be the most basic species in solution. ClCH2 CH2 Cl, CH2 Cl2 or THF with
In divided cells, it is therefore often ob- perchlorate supporting electrolytes favor
served that (1) the charge consumption in the formation of ketones [12]. In general,
an exhaustive electrolysis is lower than ex- EGA-catalyzed reactions give higher yields
pected, (2) the chemical yield of the product (70–90%) and shorter reaction times than
is low, and (3) some substrate is recov- reactions carried out with conventional
ered after addition of the base or during acid catalysts in CH2 Cl2 or with BF3 · Et2 O
workup, since a considerable part of the in benzene [12, 27].
substrate is deactivated by protonation dur- Formation of the acetonides, Scheme 7,
ing electrolysis. For example, deactivation takes place in an acetone containing small
of the substrate takes place during anodic amounts (0.01 eq.) of a metal perchlorate.
coupling of aryl-substituted 1,4-dithiines Higher concentration of the perchlorate
14.3 Acid Catalyzed Reactions 459
R2
CH2Cl2, THF, LiClO 4
R1
Pt-anod., 0.02–0.1 F
R3
ex situ or in situ O
div. or undiv. cell 72–91%
R2 R1
MeCOMe, 0.01 eq. LiClO 4
R3
Undiv. cell, Pt-anod., 0.1–0.2 F O O
R2 R1
70–88%
R3
O
(14) ClCH2CH2Cl, TsONa/TsONEt 4 R1 R2 = R3 = Me
Undiv. cell, Pt-anod., 0.3 F
OH
70–83%
R′OH, 0.2 M XClO4 OR′ OH

OR′ R = R = H
2 3
Div. cell, Pt-anod., 0.01–0.05 F OH
R1 R1
85–95% 90–95%
R′ = H, Me, Et, n-Pr, i-Pr
R1 = alkyl, aryl R1 = EWG
Scheme 7 EGA-catalyzed ring opening of epoxides.
salt decreases the yield of acetonide and tosylated intermediate in 8% yield at

increases the yield of ketone, which has 5 ◦ C [11].
been interpreted as a competition between The EGA-catalyzed alcoholysis of sub-
trapping the carbocation with the nucle- strates of monosubstituted oxiranes takes
ophile (acetone) and stabilization/ion-pair place according to Scheme 7 with either
formation with ClO4 − [12]. Acyclic α,β- NaClO4 or Bu4 NClO4 as supporting elec-
diols may be converted to acetonides trolyte [28]. Ring opening to the more
using similar experimental conditions stable carbocation determines the site of
but with less current efficiency (85% alcohol attack. For styrene oxide, the EGA-
yield, 0.3 F for a substrate analogous to catalyzed reaction was compared with reac-
(14)) [12]. tions using AcOH, HCOOH, Cl3 CCOOH,
Formation of allylic alcohols is favored 60% HClO4 or BF3 · Et2 O as catalysts, and
by supporting electrolytes with tosylate the EGA-catalyzed reaction was found to
anions, Scheme 7, [11]. Under these con- be superior with respect to yield and re-
ditions, only small amounts of ketone action time [28]. For cyclohexene epoxide
were produced. It has been suggested and other cycloalkene epoxides, the reac-
that the role of the tosylate is as a tion was shown to be highly selective giving
nucleophile that traps the carbocation. exclusively the product with OH and OR
Elimination from this intermediate then trans. For example, cyclohexene epoxide
leads to the allylic alcohol. This expla- gives exclusively (96%) the trans product
nation is supported by isolation of the upon electrolysis in MeOH (0.003 F) [28].
Ring opening and ketone formation For substrates with strongly electron
from the tetrasubstituted oxirane, (15), withdrawing substituents, formation of
upon anodic oxidation in poorly nucleo- the allylic alcohol in good yields takes
philic solvents in a divided cell takes place place under conditions otherwise favoring
according to Eq. (1) [29]. In solvents con- ketone formation, Eq. (2) [30].
taining water (conditions A), C−C-bond
CH2Cl2, LiClO4 OH
cleavage takes place and benzophenone O /Bu4NClO4
is the main product, whereas substrate EWG
Div. cell,
rearrangement preferentially takes place EWG Pt-anod., 0.1 F
in dry conditions (B and C). Two mech- T = −78 or
−30 °C
anisms have been suggested for the re-
action in dry conditions: (1) formation EWG = COOMe, CN 88–95%
of the radical cation followed by ring (2)
opening, migration, and electron trans-
fer from the rearranged radical cation 14.3.2
to another substrate molecule (0.05 F), Reaction of Acetals, Ketones, and
that is, by electron-transfer catalysis [29] Aldehydes with Nucleophiles
and (2) EGA-induced ring opening fol-
lowed by migration and deprotonation, Another reaction type for which EGA
that is, by acid catalysis [12]. That EGA catalysis has been thoroughly explored
catalysis can take place is evident from is the reaction between organo-silicon
conditions B in which 97% of the re- nucleophiles and acetals or unprotected
arranged ketone was obtained without aldehydes and ketones [31–33]. The reac-
passage of current but simply by adding tion types are aldol condensation, allyla-
the substrate to the preelectrolyzed ‘‘wet’’ tion, cyanation, and hydride reductions
solution [12]. For conditions C, parallel depending on which of the nucleophiles
reaction pathways via electron-transfer (16) to (20) is used.
catalysis and EGA catalysis cannot be Typical reaction conditions, products,
ruled out. and yields are depicted in Scheme 8 for
acetals [32, 33].
Ph Ph Ph Ph
EGA? In general, acetals derived from alde-
Ph3C + O
Ph
O
Ph ET?
O Ph
hydes (21, R1 = alkyl, R2 = H) are more
(15) reactive than those derived from ketones
(21, R1 , R2 = alkyl), and, for example, ally-
A: in situ "wet" CH 2Cl2/THF, lations of the latter are carried out at 0 ◦ C
LiClO4/Et4NClO4, 1.2 F 30% 69% rather than at −78 ◦ C.
B: ex situ "wet" CH 2Cl2/THF, The aldol reactions of enol silyl ethers,
LiClO4/Et4NClO4, 2.5 F 97% – (16), with unprotected aromatic aldehydes
C: in situ dry MeCN, LiClO4,
0.05 F 90% 10%
also give good yields of the adducts
(1) (isolated as the silyl ether) but with
R OSiMe3 R
SiMe3 Me3SiCN Et3SiH
R′ OSiMe3 OSiMe3
(16) (17) (18) (19) (20)
R1 OMe
CH2Cl2, LiClO4/Bu4NClO4 R 52–93%
R2
Undiv. cell, 0.05–0.2 F Where relevant:
T = −78 °C O R′ erythro major isomer
(16)
O
(CH2)n OSiMe3
CH2Cl2, LiClO4/Bu4NClO4
R1 66–91%
Undiv. cell, 0.01–0.2 F
MeO Where relevant:
T = −78 °C, 0 °C R2
(17) erythro major isomer
R1 OMe
1 (18) CH2Cl2, LiClO4/Et4NClO4 R
R OMe 78–98%
R2
Undiv. cell, 0.03–0.2 F
2 OMe
R T = 0 °C
(21)
(19)
CH2Cl2, LiClO4/Et4NClO4 R1 OMe

2 72–93%
Undiv. cell, 0.01–0.4 F R CN
(20) T = 20 °C
CH2Cl2, LiClO4/Bu4NClO4 R1 OMe

74–95%
Undiv. cell, 0.02–0.06 F R2 H
T = 0 °C
Scheme 8 EGA-catalyzed addition of C-nucleophiles to acetals.
a lower erythro : threo ratio than the Acetals of benzaldehydes may undergo
corresponding acetal. For reaction of EGA-catalyzed aldol reactions also with
benzaldehyde with cyclohexanone enol alkyl enol ethers, (22) (R = alkyl), as
trimethylsilyl ether, a ratio of 69 : 31 was nucleophiles [31] but in contrast to the
obtained whereas the corresponding acetal reaction with enol silyl ethers the
gave a ratio of 86 : 14 [33]. threo isomer is favored in this case,
OMe O OMe O
OMe OR MeCN, NaClO4/Bu4NClO4
(1 : 1)
Ph + +
OMe Ex situ in
CH2Cl2, T = −78 °C
(22) Yield
R = Me: 35 : 65 95%
R = SiMe3: 86 : 14 93%
Scheme 9 EGA-catalyzed diastereoselective aldol reaction of acetal with an enolether.

Scheme 9. Reaction with alkyl enol ethers CF3 compounds like (23) in which
is unsuccessful for acetals of aliphatic the sulfur substituent stabilizes the
aldehydes [31]. carbocation, β-allylation and -cyanation
The cyanation reactions with (19) is possible, Scheme 10. Normally, β-
(extremely toxic and requires essentially substitution of CF3 compounds is prob-
nonacidic reaction conditions) can also lematic because of competing elimina-
be carried out with unprotected aldehy- tion [34].
des in good yields but with higher charge Reaction of (24a) or (24b) with (16),
consumption (88–97%, 0.15–0.45 F). For (18) or (19) under the conditions of
ketones, the products are isolated as EGA catalysis leads selectively to substi-
trimethylsilyl ethers, whereas for alde- tution in the 2-position, Scheme 11, via
hydes the silyl ethers are hydrolyzed to the common cationic intermediate. Reac-
alcohols [33]. tion with O- (or S-) nucleophiles such
Allylations do not work for unpro- as MeOH, Scheme 11, exclusively gives
tected aldehydes, and reactions with substitution in the 4-position [35]. The
(20) have only been reported for ac- difference in regioselectivity has been in-
etals of aromatic aldehydes [33]. For terpreted as 2-substitution arising from
R
R
OAc CH2Cl2, LiClO4/Bu4NClO4
82–88%
CF3 + SiMe3 CF3
Div. cell, 0.03 F, ex situ
SPh SPh
(23)
Scheme 10 Allylation of α-phenylthio acetates.
OMe
(18) CH2Cl2, LiClO4/Bu4NClO4 73% + 18%

N N
COOEt COOEt
N OMe
OMe
COOEt MeOH, LiClO4/Bu4NClO4
(24a) 87%
N
COOEt OMe
OMe
CH2Cl2, LiClO4/Bu4NClO4
+ (18) 44% + 25%
N N N OMe
COOEt COOEt COOEt

(24b)
Scheme 11 Regioselective EGA-catalyzed allylic substitution.

kinetic control and 4-substitution from stoichiometric amounts of Lewis acids

thermodynamic control [35]. The MeOH such as TiCl4 , Ti(O-i Pr)4 , SnCl4 or trityl
(or Me3 SiOMe) liberated during the reac- salts but catalytic amounts of EGA can
tion with Me3 SiNu in CH2 Cl2 gives rise to be used instead, Scheme 13. The silyl
the 4-methoxy-substituted side product. adducts formed are easily hydrolyzed to
Reductive cleavage of glycosides is con- ketones and the threo/erythro ratios are
ventionally carried out using moisture- similar to those obtained using Lewis acid
sensitive Lewis acids such as BF3 · Et2 O, catalysts. Ketene silyl acetals may be used
BuSnCl3 or Me3 SiOTf. The EGA equiv- as nucleophiles with similar yields under
alent does not work with Et3 SiH as the identical conditions [37].
H-donor but good yields are obtained us-
ing the conditions of Scheme 12. Small 14.3.4
amounts of water decelerate the reaction Functional Group Protection
but the products are identical [36].
Protection of a carbonyl function as the
14.3.3 1,3-dioxolane can be efficiently carried
1,4-Addition to Enones out with 1,2-bistrimethylsiloxyethane and
EGA catalysis, Scheme 14 [38]. Application
Selective formation of 1,5-dicarbonyl com- to 1-menthone leads to 91% of the acetal
pounds by 1,4-addition (Michael addition) without epimerization at C-2. The reaction
of enolates to enones is facilitated by the is not efficient for conjugated enones [38].
use of enol silyl ethers as enolate equiv- Protection of alcohols with 3,4-dihydro-
alents [37]. The reaction is catalyzed by 2H -pyran can be carried out by EGA
CH2OMe CH2OMe
OMe H
O CH2Cl2, Zn(ClO4)2 O
OMe + BH3 • SMe2 OMe Quantitative
Undiv. cell, Pt-anod.
OMe H OMe H
OMe OMe
Scheme 12 EGA-catalyzed reductive cleavage of glycosides.
OSiMe3
O
OSi(R)Me2 CH2Cl2, LiClO4/Bu4NClO4 O
+ Undiv. cell, Pt-anod., 0.05-0.2 F
Ph Ph
T = −78 °C, ex situ or in situ
R = Me, t-Bu 80–95%
Scheme 13 EGA-catalyzed Michael addition of enolethers.
R2 OSiMe3 R1 R2
R1 CH2Cl2, LiClO4 (0.2 eq.)
+ + Me3SiOSiMe3
Pt-anod., 0.01–0.08 F O O
O OSiMe3
90–99%
Scheme 14 Protection of a carbonyl group as 1,3-dioxolane.

catalysis by passing very small amounts in MeCN-LiBF4 has been suggested [41].
of charge, Scheme 15 [39]. The procedure In a divided cell, a small amount of
also works nicely for compounds con- charge was passed (0.015 F) and the
taining protected carbonyl groups. The reaction monitored thereafter. The rate of
corresponding deprotection, Scheme 15, is reaction increased by 40 to 60% compared
not selective when other ether functions to the rate of reaction observed under
are present in the molecule. The condi- identical conditions but without passage
tions used for deprotection can be used as of charge [41].
a general method for trans-esterification,
for example, conversion of glycerides into 14.3.6
simple alkyl esters of fatty acids in high Cyclizations
yields [39].
Most attempted conversions of (25)
14.3.5 to (26) by conventional acid catalysis
Electrophilic Aromatic Substitution (e.g. HCOOH in pentane, AlCl3 in ether
or BF3 · Et2 O in CH2 Cl2 ) lead predomi-
Instead of stoichiometric amounts of nantly to mixtures of the alkenes rather
Lewis acids (ZnCl2 , FeCl3 ), small amounts than the desired (26) (<30%) [42]. Un-
of EGA (0.003–0.03 F) may catalyze der these conditions, deprotonation of
acylation of electron-rich arenes when the cyclic carbocation species takes prece-
the electrophile precursor is used as dence over return of the OH-group or – if
solvent/co-solvent [40]. Yields in the range formed – (26) is unstable under the reac-
22 to 95% are obtained, lowest when tion conditions. A rationalization of the
o-substitution has to take place as in 1,4- successful conversion by EGA catalysis
dimethoxybenzene. The regioselectivity is in acetone is the trapping of the cy-
75 to 98% [40]. clized carbocation by acetone giving (27),
The involvement of EGA as a catalyst which is hydrolyzed to (26) (52%, 0% de),
in the nitration of naphthalene by NO2 Scheme 16. Other solvents gave none of
CH2Cl2, LiClO4/Et4NClO4 MeOH, LiClO4

ROH + ROH
Undiv. cell, Pt-anod. Div. cell, Pt-anod., 0.01 F
O RO O T = 55 °C, ex situ
0.0002–0.04 F 90–98%
72–98%
Scheme 15 Protection of alcohols.
OH
MeCOMe,
LiClO4(0.1 eq) H2O +
Undiv. cell,
Pt-anod., 0.36 F
HO
O
52% 25%
(25) + (27) (26)
Scheme 16 EGA-catalyzed cyclization.

14.4 Electrogenerated Bases 465
(26), and only metal perchlorates were ef- reactants [44]. In all cases, higher endo/exo
fective in the conversion of (25) to (26) [42]. ratios were obtained than those obtained
Cyclizations of the type in Scheme 17 by the thermal Diels–Alder reactions of the
can be carried out in concentrated sulfuric corresponding enones. For (28) (R = Me)
acid, and workup, therefore, requires with cyclopentadiene, a ratio of 50 : 1
large amounts of base. The EGA-catalyzed was obtained, which should be compared
cyclization can be carried out in solutions to 3.9 : 1 for a thermal reaction of the
that can be neutralized by a few drops enone [44].
of pyridine, since only a very small
amount of charge is necessary to complete
the cyclization process under optimal 14.4
conditions [43]. Electrogenerated Bases
14.3.7 14.4.1
Diels–Alder Reactions General Concepts
Diels–Alder reactions between dienes and Electrogenerated bases (EGBs) can be

highly reactive dienophiles such as alkyl radical anions, anions or dianions. How-
vinyl ketones can be carried out using ever, basicity is not the only general
the corresponding acetals in order to property of these species, and competing
prevent polymerization of the dienophile. reactions of EGBs are as nucleophiles or
Activation of the masked dienophiles to as single electron-transfer agents. As with
undergo ionic [4 + 2] cycloadditions with conventional bases, sterically hindered
dienes can be by EGA using the conditions EGBs are useful because proton abstrac-
in Scheme 18 [44]. Yields in the range 20 tion becomes favored over nucleophilic
to 85% were obtained depending on the substitutions and additions. In contrast to
ClCH2CH2Cl, LiClO4/Et4NClO4 major isomer

R
R R
T = 55 °C
R = CH2SO2Ph 95%
R = CO2Me 88%
R = CH CHCOCH3 57%
R = COCH CHCH3 30%
Scheme 17 EGA-catalyzed cyclization.
( )n
R CH2Cl2,
LiClO4/Bu4NClO4
R
+ 76–85%
O O + +
( )n Undiv. cell, O OH ( )n O
Pt-anod., 0.2 F R
(28) n = 1, 2 T = −78 °C n = 1, 2
O
Scheme 18 EGA-catalyzed cycloaddition.

reactions involving EGAs that are mostly 14.4.2

catalytic, many reactions involving EGBs In situ Versus Ex situ Formation of the EGB
require stoichiometric amounts of base.
Historically, the concept of EGBs was de- Formation of EGBs from deliberately
veloped in relation to electrochemically in- added PBs may be carried out in two
duced Wittig reactions [45]. Co-electrolysis ways: (1) in situ where generation of the
of the phosphonium salt and the car- EGB by reduction of the PB takes place
bonyl compound was carried out using in the presence of the reactant(s), or
the carbonyl compound as the solvent and (2) ex situ where the EGB is generated
gave reasonable yields of the alkene [45]. by exhaustive reduction of the PB followed
Most of these reactions can be ratio- by subsequent addition of the reactant(s).
The most frequently used method is in situ
nalized within Scheme 19, in which the
generation of the EGB. The advantages of
phosphonium ion participates both as
in situ generation are that the EGB can be
the probase (PB) and as the acidic sub-
short lived, and that the applied current
strate [46].
can control the amount of base present.
Ylide formation by electrochemical re-
The major disadvantage is that the PB
duction of onium ions [47–53] can in
must be more easily reduced than the
general be rationalized as resulting from
reactant(s). The use of an ex situ formed
an EGB reaction. A major disadvantage in
EGB is similar to the use of an ordinary
using the substrate as the PB is that only base. The advantage of ex situ formation
half the substrate undergoes the desired is that easily reduced reactants can be
base-induced reaction (except in cases that used in combination with EGBs generated
are catalytic, see Sect. 14.9). Of the more from PBs, which are difficult to reduce.
synthetic usefulness for reactions requir- A disadvantage is that the EGB has to be
ing stoichiometric amounts of base are stable in the solvent-electrolyte system for
the EGBs generated from PBs, which are a longer time.
different from the acidic substrates as
demonstrated first for the Wittig reaction 14.4.3
using azobenzene as the PB [46]. Kinetic Versus Thermodynamic Basicity
The ideal EGB should be (1) formed
by reduction of a cheap, nontoxic PB at One way to classify EGBs is according to
modest potential, (2) nonnucleophilic in the atom to which proton transfer takes
order to avoid side reactions, (3) easily place, typically nitrogen, oxygen or carbon.
separated from the reaction mixture, As in other proton transfer reactions,
and (4) recyclable. No single compound proton transfer to/from heteroatoms (N
or class of compounds fulfill these or O) is generally much faster than
requirements. to/from carbon when comparing reactions
R1
+ O(solvent)
2e− Ph3PCH2Ph R2 R1
+ −
Ph3P CHPh CHPh
Ph3PCH2Ph PhCH2 −Ph3PO
−PPh3 −PhCH3 R2
PB EGB
Scheme 19 Wittig reaction with a phosphonium ion as probase and as substrate.

14.4 Electrogenerated Bases 467
of similar driving forces. Often, proton quantitatively deprotonated either by an

transfer to anions or dianions is faster in situ or an ex situ-formed EGB, and
than proton transfer to radical anions S− converted to the product by addition
(assuming equal thermodynamic basicity of another reactant in a subsequent step;
and the same type of atom) due to (2) EGBH+ or S− (or both) are removed
the fact that radical anions, which are from the equilibrium in an irreversible
feasible as EGBs, generally are extensively follow-up reaction. If that is the case,
delocalized. Within different classes of the formation of products may, as with
EGBs there is, therefore, no simple ordinary bases, be efficient even when
relationship between thermodynamic and K 1.
kinetic basicities. The kinetics of proton
Using a radical anion, B−• , as the EGB
transfer to typical EGBs from different
normally ensures that the protonated EGB
types of acids is not discussed here;
[in this case a radical, BH• , Eq. (4)], is
references can be found in Refs. [3, 54].
quickly removed from the equilibrium,
The reactions discussed in the following
since neutral radicals formed by proto-
sections take place in aprotic solvents,
and reference to known or estimated nation of radical anions normally are
thermodynamic basicities will relate to more easily reduced than the precursor
DMSO unless otherwise noted, since B, Eq. (5).
DMSO is the polar aprotic solvent in
B− + HS−−− •
() BH + S
−
•
which most thermodynamic acidities have (4)
been measured [55–58]. Values of pK −• −
determined in DMSO can usually be B + BH −−−→ B + BH
•
(5)
assumed to parallel values in DMF [59, BH− + HS −−−→ BH2 + S− (6)
60], MeCN, and other polar aprotic solvents
whereas pK values (and relative pK values)
related to water and other hydroxylic The anion BH− formed in Eq. (5) is
solvents can be very different. thermodynamically a stronger base than
B−• , and BH− will react with another
14.4.4 molecule of substrate, Eq. (6). Each PB will
Efficiency of the Proton Transfer Reaction therefore consume a total of two protons
(and two electrons). Radical anion EGBs
For an EGB to work efficiently on are normally produced in situ.
a synthetic scale, the proton transfer When the EGB is an anion or a
reaction (Eq. 3) has to appear essentially dianion, irreversible follow-up reaction of
irreversible. the deprotonated substrate, S− , is the
kf only way by which an unfavorable proton
−− + −
EGB + HS −−−
− EGBH + S (3) transfer equilibrium can be driven toward
kb products. A disadvantage is that when the
Irreversibility can be obtained if (1) the follow-up reaction of S− is with an added
equilibrium constant for reaction (3), electrophile, competing reaction between
K = kf /kb , is large, that is, the EGB is the EGB and the electrophile is often
a thermodynamically much stronger base observed. Or – if the EGB is a dianion – the
than the deprotonated substrate, S− . If monoprotonated form may react with the
that is the case, the substrate may be electrophile.
14.4.5 the radical anion [65], [pK(Ph-NH-NH-

Comparison of EGBs with Ph) 26.1, pK(Ph-NH-N− -Ph) ≈ 31, pK(Ph-
Conventional Bases NH-N• -Ph) < 20]. Azopyridines, (30), are
in general more easily reduced to dianions
In contrast to EGAs, most of the syn- than (29) but the dianions are also less
thetically useful reactions involving EGBs basic [64, 66, 69].
are reactions requiring stoichiometric Using the dianion as an EGB may result
amounts of the electrogenerated reagent, in mono- or diprotonation depending
Sect. 14.8, and the major advantage of on the strength of the acid, whereas
strong EGBs compared to strong con- the radical anion EGB always results in
ventional bases is the recycling aspect. diprotonation, cf. Eqs. (4 to 6). Upon
Whereas strong conventional bases typi- workup, the resulting species is always
cally are expensive reagents that can be the dihydro product, and a disadvantage
used only once, many of the strong EGBs of (29a) as a PB on a multigram scale
are converted directly into their PB, or is the conversion of its dihydro product,
the PB can be obtained rather easily hydrazobenzene, into the carcinogenic
by reoxidation. For base-catalyzed reac- benzidine on acidic aqueous workup.
tions, Sect. 14.9, particularly the recent, This inconvenience is avoided by using
elegant uses of dioxygen, O2 , as a PB (29b–c) that also show enhanced basicity
are promising. of the EGBs (radical anions or dianions).
Another disadvantage of (29a) as a PB
is that both (29a)−• and (29a)2− are
14.5 good nucleophiles (see Sect. 14.8.5 for
Nitrogen Bases an example).
Nitrogen heteroaromatics are expected
14.5.1 to be useful probases. The cathodic
Azo Compounds and Nitrogen reduction of phenazine, (31), resembles
Heteroaromatics as Probases closely that of (29a) [70, 71], and the kinetic
basicity of (31)−• is comparable to that of
Azobenzenes, (29), and analogous het- (29a)−• [54]. However, application of (31)
eroaromatic azo compounds, (30), are in as a PB in electrosynthesis has not been
aprotic solvents reduced in two sequential reported, and there is only a single report
one-electron steps to the radical anion and concerning the use of the radical anion of
the dianion [61–66]. Disproportionation of acridine, (32), as an EGB [72].
the radical anion to the dianion is favored
by the presence of Li+ [67]. The dianion 14.5.2
is considerably more basic than the radi- Amides as Probases
cal anion, and the dianion is only stable
in very dry nonacidic solvents [64, 65, 67, The application of 2-pyrrolidone, (33H),
68]. Both the dianion and the radical anion as a PB is widespread (see Sects. 14.8
derived from (29) have been used as EGBs. and 14.9). The 2-pyrrolidone anion, (33)− ,
The anion resulting from protonation of is formed by direct cathodic reduction
the dianion is less basic (by several pK (≈−2.5 V), Scheme 20, and therefore nec-
units) than the dianion but more basic than essarily has to be used as an ex situ
14.5 Nitrogen Bases 469
R2
N
R1 N N
N N N N
R1
N
R2 N
(29) (30) (31) (32)
a:R1 =R2 =H
b: R 1 = alkyl, R2 = H
c: R 1 = R2 = alkyl
DMF, R 4NX
+
O Div. cell O , R4N + ½ H2
N N
1.5 F(typical) −
H (33)−
(33H)
pK 24.1
Scheme 20 2-Pyrrolidone as probase.
reagent. The anion is a strong base, pK(2- The polyacrylamides could be repeatedly
pyrrolidone) 24.1. reused [74].
An alternative procedure (constant cur- A stronger base and notably weaker
rent, undivided cell, stainless steel cathode, nucleophile is the anion of hexamethyl-
sacrificial magnesium anode) has later disilazane (Me3 Si)2 NH, (34H). The an-
been developed for ex situ preparation of ion, (34)− , is electrogenerated ex situ,
(33)− from (33H) [73]. The solution of the similarly to (33)− , as its magnesium
Mg2+ -stabilized (33)− may be stored at salt in dimethoxyethane with 15% v/v
room temperature for up to 10 h. The sol- HMPA [75]. The PB (34H) is commercially
vent used, dimethoxyethane with 10% v/v available, relatively cheap, and in many
HMPA, raises problems since in many respects behaves very much like lithium
laboratories HMPA is a banned substance diisopropylamide (LDA). Substitution of
because of its carcinogenicity. The HMPA HMPA with N -methyl-2-pyrrolidone was
is required to give acceptable conductivity not successful [75].
in the preparation of the EGB but is also Since formation of EGBs from amides,
crucial in avoiding strong ion pairing be- in all cases, is the result of direct re-
tween Mg2+ and the EGB (which decreases duction and H2 formation (and has to
the reactivity of the EGB) [73]. However, it be done ex situ), the monomeric as well
is reported that HMPA may be replaced as the polymeric EGBs are recovered as
with Me2 N(CH2 )2 NMe2 as a complexing the PB. Their reactions as bases have
agent [73]. to be driven either by a thermodynami-
The advantages of polymer-supported cally favored proton transfer reaction or
reagents have been exploited for EGBs by a fast follow-up reaction of the depro-
in the form of EGBs generated from tonated substrate, which – particularly for
polyacrylamides [74]. The effective base is (33)− – is difficult, since (33)− is a good
in all cases an amide anion similar to (33)− . nucleophile.
14.6 air-saturated solutions serves as the PB

Oxygen Bases source. This approach prevents oxidative
follow-up reactions.
14.6.1
Dioxygen as Probase
14.6.2
Phenols as Probases
Dioxygen is conveniently reduced to the
superoxide anion, O2 −• , by reduction at
Hindered phenolates have low nucle-
about −1.0 V (vs. SCE) in MeCN or DMF.
ophilicity and may in aprotic solvent act
The properties of O2 −• have been re-
as EGBs. The tetraethylammonium pheno-
viewed [76–78]. Its basic properties stem
late of (35H), (pK ≈ 16.8) can be formed ex
from the driving force of the disproportion-
situ by direct reduction of (35H) [80, 81],
ation [78], Eq. (5). The O2 −• is a relatively
similar to Scheme 20. Since the thermo-
weak base (pK(HO2 • ) ≈ 12 in DMF) [79]
dynamic basicity is low, the applicability
but the overall equilibrium constant for
as an EGB is entirely dependent on the
reaction (7) is in the order of 105 for
removal of deprotonated substrate by fur-
simple alcohols and water (pK ≈ 30) in
ther reaction.
DMF [79]. However, for such highly en-
dergonic reactions, the rate-determining 14.6.3
protonation of O2 −• is a slow reaction with Carbonyl Compounds as Probases
a second order rate constant of around
10−3 M−1 s−1 [79]. An alternative route to phenolate-like
−• −− − − EGBs is through the cathodic reduction
2O2 + HS−−−
−HO2 + S + O2 (7)
of quinonemethides, (36), [82, 83]. The
The common method of O2 −• gener- advantage of these PBs is that they are
ation is by bubbling O2 through the reduced at modest potentials, which allow
catholyte during reduction, and an ex- EGB formation to take place in situ, and
cess of O2 is therefore present. Car- they are ultimately converted into phenols
banions formed by proton transfer to that are easily reoxidized to (36) either
O2 −• may therefore react with O2 , by air or by anodic oxidation (60–70%
and many synthetically interesting re- yield) [82]. The radical anion (36a)−• is
actions involve not only deprotona- expected to have basicity similar to that
tion but also oxidative follow-up reac- of (35)− , whereas the pK of the conjugate
tions of the deprotonated substrate (cf. acid of the dianion formed by further
Sect. 14.8.7). For several base-catalyzed reduction can be assumed close to that
reactions (Sect. 14.9) the O2 present in of triphenylmethane, 30.6.
OH O
tBu tBu (36a): R 1 = t-Bu, R2 = R3 = Ph
R1 R1
(36b): R 1 = t-Bu, R2, R3 = 9-fluorenylidene
O
(36c): R 1 = t-Bu, R2 = H, R3 = R1 R1
R2 R3
(35H) (36)
CH
14.7 Carbon Bases 471
The electrochemical behavior of (36a) 14.7.1

has been studied in some detail [83]. Pro- Activated Alkenes as Probases
tonation of (36a)−• (at oxygen) gives a
radical, which in contrast to the radicals Esters of ethenetetracarboxylic acid, (37),
formed by protonation of (29)−• –(32)−• , and disubstituted (fluoren-9-ylidene)me-
is more difficult to reduce (by ca. 0.1 V) thane derivatives, (38), are reduced sequen-
than (36a) [83]. The reaction sequence in tially to radical anions and dianions [2, 68,
Eqs. (5) and (6) is therefore not followed 84, 85]. Only the dianions are sufficiently
for (36a). basic to be useful as EGBs [53, 86]. For (37),
Radical anion EGBs derived from aro- the two reduction potentials are separated
matic carbonyl compounds are expected by 0.2 V [68], and even with a working
to be relatively weak bases but since the potential allowing formation only of the
radical anions undergo dimerization, the radical anion, the dianion can be formed by
more basic dimer dianions may be active disproportionation. The protonated form
as EGBs for substrates with pK values of the dianionic EGBs, (37H)− and (38H)− ,
in the range 20 to 23. Aromatic carbonyl will normally be stable in solution since
compounds have primarily been used as the pK values of the dihydro products are
PBs in catalytic reactions in which the expected to be in the range 12 to 16.
PB also functions as an electrophile (cf. The more hindered (37c) is to be
Sect. 14.9.2). preferred; the PB is less susceptible to
Michael addition and (37c)2− as well as
(37cH)− are less nucleophilic than those
of the lower esters (see Sect. 14.8.5 for an
14.7
example). In the absence of side reactions
Carbon Bases
these PBs are, upon workup, converted
into the dihydro derivatives that can be
Two types of electrogenerated carbon bases reoxidized back to the PBs by bromine or
have commonly been used: (1) dianions by anodic oxidation [68, 87, 88]. The base
derived from activated alkenes, and strength of (38)2− can be modified either
(2) carbanions formed by reductive cleav- by substitution [89] or by complexation
age of halogen compounds or by di- with alkali metal counterions [86, 89].
rect reduction of weak carbon acids. In
both cases, the efficiency of the proton 14.7.2
transfer reaction relies on a thermody- Carbanions as EGBs
namically favored proton transfer or a
fast follow-up reaction of the deproto- Like the formation of anionic EGBs by di-
nated substrate. rect reduction of weak nitrogen or oxygen
R1 R2
a: R 1 = R2 = CN, X = Y = CH
b: R 1 = CN, R2 = COOEt, X = Y = CH
ROOC COOR a: R = Me
b: R = Et X c: R 1 = R2 = COOEt, X = Y = CH
ROOC COOR c: R = Bu d: R 1 = R2 = COOEt, X = N, Y = CH
Y Y
(37) e: R 1 = R2 = COOEt, X = H, Y = N
(38)
acids, formation of carbanion EGBs by and proton transfer to carbon in a de-

direct reduction of weak carbon acids nor- localized radical anion is normally slow
mally requires ex situ conditions, since (cf. Sect. 14.4.3). There are very few cases
most reactants are reducible at the re- of aromatic hydrocarbons being deliber-
quired potentials. Triphenylmethane, (39), ately used as PBs in electrosynthesis but
a very weak acid (pK 30.6), is directly an interesting analogue involves reduction
reducible to the corresponding strongly ba- of the fullerene C60 [94]. This compound
sic and nonnucleophilic triphenylmethyl can fairly easily be reduced sequentially
carbanion in dry conditions at low temper- to mono-, di-, and tri-anions of increas-
ature [80, 90]. ing basicity. The fullerene is in principle
The phenyl σ -anion is strongly basic recyclable but may also be reused in situ
but may be obtained at relatively modest since the partially hydrogenated forms can
potentials by reductive cleavage of haloben- also work as PBs [94]. However, C60 is
zenes when the right cathode material is very poorly soluble in polar solvents and
chosen [63]. Typically, the reactions are the practical use of C60 as PB is limited
carried out at constant current in undi- to base-catalyzed reactions in which only
vided cells using Cd-coated Ni-cathodes, Al very small amounts of PB is required, see
or Mg sacrificial anodes, DMF (or MeCN Sect. 14.9.1.
for cyanomethylation) as the solvent and
Bu4 NBF4 as the electrolyte. Under these
conditions, iodobenzene is reduced at 14.8
−1.6 V versus SCE and bromobenzene Reactions Consuming Stoichiometric
at −1.9 V, which may allow their use in Amounts of Base
situ [63, 91–93].
In most other cases, direct reduction 14.8.1
of carbon acids has been used as a path- Wittig Reactions
way for generation of nucleophiles and not
EGBs. Easily reduced halogen compounds Wittig reactions have frequently been used
have occasionally been used as PBs. The to test and compare new EGBs, typically
EGBs are identical to those obtained by stilbene formation in the EGB-induced
direct reduction of the conjugated acid; Wittig reaction of the relatively acidic
an advantage being that reduction and Ph3 P+ CH2 Ph (pK 17.4) with PhCHO. A
cleavage of the halocompound normally selection of results is shown in Table 1,
is easier and therefore may allow in situ and there appears to be large inconsis-
formation. However, these EGBs are only tencies in the yields and in the trans/cis
moderately basic. ratios obtained under apparently identical
conditions. The effect of changing the sup-
14.7.3 porting electrolyte cation from Bu4 N+ to
Other Electrogenerated Carbon Bases Li+ also appears to be nonsystematic.
The easy formation of (38)2− has
Cathodic reduction of aromatic hydrocar- (particularly in the presence of Li+ ) been
bons gives π-radical anions, which are shown to be useful for the synthesis of cis-
possible EGBs. However, the PBs normally rich mixtures of alkenes whilst stronger
have low solubilities in polar aprotic sol- bases such as KOBut or BuLi essentially
vents, relatively low reduction potentials, give the trans product [86].
14.8 Reactions Consuming Stoichiometric Amounts of Base 473
Tab. 1 Yields and stereochemistry of stilbene as a function of the EGB and the reaction
conditions in the Wittig reaction of Ph3 P+ CH2 Ph with PhCHOa
EGB Supporting Yield (trans/cis) References

electrolyte
(29a)−• /(29a)2− b LiCl 98% (0.66) 46

(29a)−• Bu4 NBF4 79% (0.5), 78% (0.5)c , 96% (0.5)d 95
(36a)−• Bu4 NClO4 99% (1.9) 82
Bu4 NBF4 58% (0.59) 95
(36b)2− Bu4 NClO4 48% (1.0) 82
(36c)2− Bu4 NClO4 84% (1.3) 82
(38a)2− Bu4 NBF4 80% (0.63), 46% (1.6) 95, 86
LiClO4 74% (0.69), 74% (1.44) 86, 53
(38b)2− Bu4 NBF4 68% (1.0) 86
LiClO4 94% (1.2) 86
(38c)2− Bu4 NClO4 80% (9.0) 89
(38d)2− Bu4 NClO4 91% (1.0) 89
(38e)2− Bu4 NClO4 87% (4.0) 89
a General conditions: DMF as solvent and in situ formation of the EGB by constant potential
electrolysis (CPE) at the potential of EGB-formation in a divided cell.
b Disproportionation of (29a)−• to (29a)2− in the presence of Li+ cannot be excluded.
c Constant current electrolysis (CCE).
d CCE in DMSO as solvent.
Wittig–Horner reactions between alkyl gives similar yields of the alkene [97].
phosphonates and aldehydes can be The successful use of (36a) as a PB
carried out similar to the Wittig reaction for deprotonation of (EtO)2 P(O)CH2 Ph
but the phosphonates are much weaker (pK 27.6) and formation of stilbene
acids than the phosphonium cations (trans/cis = 9) in the presence of
[by 9–10 pK units when comparing benzaldehyde [82] is hardly due to (36a)−• .
Ph3 P+ CH2 X with (EtO)2 P(O)CH2 X], and, More likely, initial O-protonation of
therefore, stronger electron-withdrawing (36a)−• by an acidic impurity gives
substituents, X, [96] or more basic EGBs the radical that is further reduced at
are required. Using (29) as a PB the working potential (lower than that
in situ gives, in the presence of of 36a−• formation), and the much
p-methoxybenzaldehyde, the alkene in more basic substituted triphenylmethyl
60 to 80% yield for phosphonates anion deprotonates the phosphonate.
(EtO)2 P(O)CHXY with Y = H, X = The reaction is then sustained by the
COOEt, CN, Ph, and Y = Me, X = protonation of a new (36a)−• by the dihydro
COOEt, Y = X = Cl, exclusively (or almost product, (36aH2 ).
exclusively) as the E isomer [96]. This Only low yields (10%) of coumarin
approach may be compared to the direct were obtained by the intramolecular Wit-
reduction (at Pt or GC cathodes) of the tig–Horner reaction of 2-(diethoxyphos-
phosphonates to give H2 and the anion, phorylacetoxy)benzaldehyde using (35)−
followed by addition of an aldehyde, which as an EGB (formed ex situ in MeCN) [98].
14.8.2 also been carried out using in situ gener-

Addition to Aldehydes and Ketones ated Ph− as the EGB in DMF-Bu4 NBF4 .
The PB had to be present in excess to
Ex situ formation of (33)− followed by achieve full conversion of the aldehyde.
addition to a mixture of CHCl3 and alde- Moderate to good yields were obtained [93].
hyde (aliphatic or aromatic) in DMF at DMF as a solvent seems to be crucial for
low temperature leads to deprotonation the stability of ‘‘CF3 − ’’, and trapping of
of CHCl3 but not of the aldehyde, and CF3 − by DMF to form an aminoalco-
formation of the trichlorocarbinol takes holate has been suggested as the initial
place without formation of side products step in the mechanism. Thereafter, the
by aldol condensation, Scheme 21 [99]. ‘‘CF3 − ’’ is transferred to the more pow-
The reaction could also be carried out erful electrophile, the aldehyde or the
(75–86% yield for butanal) using poly- ketone [101, 102].
meric amides as a PB and with similar
conditions [74]. 14.8.3
The relatively easy formation of Ph− Alkylation of Activated
from PhI (cf. Sect. 14.7.2) allows EGB Methylene Compounds
formation in situ and gives trichloromethy-
lation of aldehydes in 48 to 61% yield at In general, deprotonation of the substrate
by reaction with an EGB has to take
room temperature [91]. A similar proce-
place in a separate step before addition
dure was used for reaction of CF3 CCl2 H
of the alkylating agent, since compet-
and CCl3 CCl2 H with aldehydes [91].
ing alkylation of the EGB may otherwise
Trifluoromethylation of carbonyl com-
take place. In order to minimize the
pounds could be carried out by a procedure
time between deprotonation and alky-
similar to Scheme 21, the only differences lation, a three-step procedure is often
being that the reaction was carried out at used: (1) ex situ formation of a strongly
−50 ◦ C, CF3 H (gas, very weak acid, es- basic EGB, (2) addition of the EGB to
timated pK 25–28) was added in a larger the substrate, which is quantitatively de-
excess, and Bu4 N+ or Oct4 N+ counterions protonated, and (3) trapping of the de-
rather than Et4 N+ were necessary [100]. protonated substrate with the alkylating
Yields were good (60–92%) with aro- agent.
matic aldehydes. For ketones, good yields Selective monoalkylation of methyl aryl-
(60–85%) were only obtained when the al- acetates by alkylhalides is difficult with
coholate was trapped as the trimethylsilyl conventional bases. It may be achieved
ether by hexamethyldisilazane. Aliphatic by application of the three-step proce-
aldehydes gave poor yields [100]. Trifluo- dure outlined above adding (33)− to the
romethylation of aromatic aldehydes has methyl arylacetates at a low temperature
O OH
DMF, −78 °C
CHCl3 + + , Et4N+ R H 50–80%
R H N − O (−33H)
− CCl3
R = alkyl, aryl (33)−
Scheme 21 Trichloromethylation of aldehydes with 2-pyrrolidone as probase.

(−78 ◦ C). The substrate is deprotonated generated (33)− with Mg2+ as counter-
[pK(PhCH2 COOMe) 22.7] and trapped ions forming enolates stabilized by Mg2+ ,
by an alkyliodide (−78 ◦ C). This proce- whereas dialkyl ketones (pK 27–28) do not
dure leads selectively to mono α-alkylation react [73, 106]. Under the conditions in
(81–99%) [103]. Selective monoalkylation Scheme 22, the enolates equilibrate to the
of β-diketones in 70 to 95% yield was more stable Z-enolates that can be trapped
obtained by a similar procedure, and by an excess Me3 SiCl. The presence of
only in a few cases (bulky secondary HMPA is crucial for the equilibration [73].
alkylhalides) were the O-alkylated sub- The regioselective monoalkylation of 2-
strate found as a side product. Tetraalky- methylcyclopentanone, (39), via the eno-
lammonium counter cations were nec- late is difficult to achieve with conventional
essary in stabilizing the enolate; Na+ bases but can be carried out using a slightly
counter cations did not give selective C- modified procedure, where 4 eq. of MeI is
alkylation [104]. added to the EGB solution and (39) is added
It may be difficult to alkylate α- dropwise at −50 ◦ C. Formation of the 2,2-
CF3 enolates since they easily undergo dimethylcyclopentanone takes place but
defluorination prior to trapping with conversion is low since some of the EGB is
the alkylating reagent. The enolate of methylated [106], Scheme 22. The conver-
dimethyl trifluoromethylmalonate gener- sion may be improved by subjecting the
ated by (33)− /Et4 N+ was shown to be product mixture to another cycle of reac-
stable towards defluorination and could tion since the product is too weakly acidic
be alkylated in 30 to 80% yield depending to be deprotonated by the EGB.
on the alkyl halide [105]. Using the more basic and less nucleo-
Less reactive compounds such as alkyl philic EGB (34)− also leads to depro-
benzyl ketones and cycloalkanones (pK tonation, Scheme 22, but trapping with
20–26) may be deprotonated by ex situ Me3 SiCl predominantly gives products
2+
N O ½Mg O OSiMe3 OSiMe3
− Me3SiCl
(33)− excess Total
+
−75 °C, 3 h yield: 100%
DME/HMPA
91% 9%
½Mg2+
O N O
(39) added − O O
dropwise (33)−
Total
+
−50 °C, 4 eq. MeI Me yield: 49%
(39) DME/HMPA
82% 18%
Me3Si SiMe3 ½Mg2+

N O OSiMe3 OSiMe3
− Me3SiCl
(34)− excess Total
+
−75 °C, 3 h yield: 90%
DME/HMPA 91% 9%
Scheme 22 C- or O-alkylation of an enolate formed by an EGB.

arising from the removal of the most acidic 14.8.4

hydrogen (kinetic control). Equilibration of Cyanomethylation
the enolate to the more substituted isomer
does not take place [75], probably because Formation of β-oxonitriles by cyanomethy-
of the fast, quantitative deprotonation leav-
lation of esters requires that the ester
ing no unreacted ketone as is necessary for
contains no α-hydrogens since the acid-
equilibration.
ity of MeCN (pK 31.3) is comparable to
Alkylation of 2-methylcyclohexanone
the acidity of the α-hydrogens of the es-
could not be achieved by the procedure
ter. A strong EGB such as Ph− produced
used for (39) since it is a weaker acid.
in situ using MeCN as the solvent and in
Good yields (38–84%) of the 2-alkyl-2-
the presence of esters lacking α-hydrogens
methylcyclohexanone were obtained from
leads to nucleophilic acyl substitution [63,
2-methylcyclohexanone using the strongly
92], Scheme 23. It is crucial that the an-
basic trityl anion as an EGB (gener-
ated ex situ by reduction of Ph3 CH, in ionic intermediate, (40), is stabilized by the
DMF-Bu4 NBF4 at −50 ◦ C) followed by anodically produced Mg2+ , since the final
addition of alkyl or benzyl iodide or bro- β-oxonitrile is far more acidic (pK ≈ 12)
mide [80, 90]. This EGB is a stronger base than MeCN. The same procedure could
than (33)− and the enolates formed (with be used for cyanomethylation of ketones
R4 N+ counterions) are more reactive than and aldehydes to give β-hydroxynitriles
those stabilized by Mg2+ in Scheme 22. (55–74%) [92].
Only with MeI as the alkylating reagent, Attempts to prepare − CH2 CN before
2,5-dimethylcyclohexanone was the dom- adding the electrophile did not lead to
inating regioisomer [90]. Monoalkylation cyanomethylation since − CH2 CN reacts
of cyclohexanone and fluorene could with MeCN prior to addition of the
be carried out using the same proce- electrophile, and the type of products
dure [90]. isolated (20–88%) depended on the elec-
A one-pot conversion of EtOOCCH2 CN trophile [92].
and ClCOOEt initially to (EtOOC)2 CHCN When more acidic nitriles such as
using (29a) as PB, and then to PhCH2 CN (pK 21.9) are used (in DMF)
(EtOOC)2 C=O (77%) by O2 −• /O2 with in situ produced Ph− as the EGB,
according to the third reaction in esters with α-hydrogens can also be
Scheme 28 (Sect. 14.8.7) has been used as electrophiles. Formation of β-
reported [107]. oxoesters may be carried out in a similar
2 F, undiv. cell
PhBr Ph− + Br−
Cd-Ni cath., Mg anod.
O
R′ O− Mg2+ Acidic O
R O work up
Ph− + MeCN −CH CN
2 R OR′ CN + R′OH
−PhH R
CN 60–83%
R = t-Bu, Ar, R″CF2
(40)
R′ = alkyl
Scheme 23 Cyanomethylation using Ph− as EGB.

fashion using, for example, PhCH2 COOEt as well, and the subsequent alkylation of
(pK 22.7) instead of PhCH2 CN or the carboxylated ethyl phenylacetate also
MeCN [63]. leads to alkylation of (37aH)− , Scheme 24.
Whether the dianion of azobenzene Smaller amounts of the side products are
is able to deprotonate MeCN (pK 31.3) obtained using the more bulky (37b)2− as
has been discussed [62, 64, 68]. However, an EGB and using (37c)2− effects clean
on a preparative scale generation of carboxylation and alkylation of (41H),
− CH CN takes place at the potential of
2 Scheme 24, [68]. In none of the cases,
the second reduction of azobenzene, and products derived from carboxylation of the
reactions initiated by cyanomethylation EGBs were found. This, however, was the
of benzamide [108], carbonyl compounds case using (29a) as a PB. Although (29a)2−
(or their Schiff bases) or α,β-unsaturated is able to deprotonate (41H), the only
nitriles either present in situ [69, 109] product isolated was dicarboxylated and
or added subsequently [110–112] have alkylated azobenzene. The more sterically
been studied. A mixture of products is hindered (29b) (R1 = t-Bu) used as a
normally obtained. PB gave the intended product [68]. Both
(29a)−• and (29a)2− are also easily alkylated
14.8.5 by MeI [67].
Carboxylation In the carboxylation of the less acidic
diglycolic acid N -methylimide, (37b)2−
The advantages of sterically hindered PBs was found to be superior to (29b)2−
have been demonstrated for the series (R1 = t-Bu) as an EGB since the latter
(37a–c). The dianionic EGBs are all partially underwent cleavage of the N–N-
able to deprotonate ethyl phenylacetate, bond [113].
(41H), (pK 22.7), and the anion (41)− is A surprising N -carboxylation of amines
carboxylated in the presence of CO2 [68]. and anilines using (33)− as EGB in MeCN-
Using (37a)2− as an EGB, the product of Et4 NClO4 has been reported [114]. Despite
Michael addition of (41)− to (37a) is formed the fact that amines and anilines have pK
1. 2.
DMF, R 4NX, CO2 EtI COOEt
Ph
(29b) (R = t-Bu)
2− 1
COOEt
or (37c)2−, in situ
77–78%
Ph COOEt
PhCH2COOEt 1. DMF, R 4NX, CO2 2. EtI
(41H) N N
(29a)2− in situ
pK 22.7
EtOOC 64% Ph
COOEt
1. DMF, R NX, CO 2. EtI Ph MeOOC COOMe
4 2 COOMe +
MeOOC COOEt
(37a) 2−
in situ COOMe
MeOOC COOMe
MeOOC
31% 11%
Scheme 24 Advantage of a sterically hindered probase in carboxylation of ethyl phenylacetate.

values in the range 30 to 40 (while 33H of the methylene compound but com-
has pK 24.1), a yield of 30 to 90% of the peting reduction of the halogen com-
alkyl or aryl carbamates were obtained by pound normally leads to low yields [117].
stepwise addition of the amine, CO2 , and Higher yields are obtained using an
EtI to the ex situ formed EGB [114]. easily formed EGB for the deprotona-
The acidity of the N -protons in amides tion step. Using (29a) as the PB in
is considerably higher (pK typically in the MeCN-Bu4 NClO4 α,α-diactivated methy-
range 20–26) than those of amines, and lene compounds (XCH2 COOEt, X = Ac,
(37b)2− has been successfully used as CN, COOEt) gave, in the presence
in situ formed EGB for N -carboxylation of 1,2-dibromoethane, 80 to 85% of
and subsequent cyclization of amides with the cyclopropane product [117]. An in-
leaving groups in the α-position according tramolecular version of the same re-
to Scheme 25 [115]. action type using (29a) as the PB in
DMF-Bu4 NBr gave 80 to 82% yield of
the 1,1-dicarbomethoxycycloalkanes when
14.8.6
Br(CH2 )n CH(COOMe)2 (n = 4, 5) were
Cyclizations
used as substrates [118].
Direct reduction of O-tosylglycolamides
Formation of 12 to16-membered lactones
leads to cleavage and loss of the tosyl group
in 66 to 75% yield from the corresponding
but in situ formation in DMF of EGBs de-
ω-bromo carboxylic acids can be carried
rived from (29a) or from Me2 CBrCOOEt
out by addition of a solution of ex situ leads to deprotonation of the amide nitro-
formed (33)− to a dilute solution of gen. The amide anion acts as a nucleophile
the carboxylic acid at low temperature toward unreacted starting material; further
(−60 ◦ C) [116]. A crucial point in the deprotonation takes place followed by cy-
selective reaction seems to be R4 N+ , clization to the diketopiperazine. However,
which stabilizes the carboxylate ion and small amounts of the oxazolidinone aris-
slows down bimolecular reactions for ing by nucleophilic attack on DMF is also
steric reasons. The yield of the cyclic formed, Scheme 26 [119].
product increases with increasing size of
R [116]. 14.8.7
Formation of cyclopropane derivatives Oxidative Conversions
by reaction between an α,β-dihalo com-
pound and an acidic methylene com- Homocoupling of aryl acetic acid deriva-
pound can, in principle, be initiated by tives has been achieved by deprotona-
direct cathodic formation of the anion tion and oxidation by I2 as outlined
O
O
X DMF, Et 4NClO4, CO2 R′ R
NHR N
(37b)2− in situ
R′ O
O
X = Cl, Br, OSO 2C6H4CH3(p) 40–99%
R = alkyl, allyl, benzyl, phenyl
R′ = H, Me
Scheme 25 N−carboxylation of amides using EGB.

O
O
O O TsO
EGB NH Ph NH Ph
TsO TsO
NH Ph N Ph −OTs Ph N
− OTs
1. EGB O
DMF 2. −OTs
O O
O
N Ph TsO
N Ph N Ph
O −OTs Ph N
NMe2 −O NMe2
10–15% O 60%
Scheme 26 Dimerization and cyclization initiated by deprotonation of an amide by EGB.
Ph COOMe
(33 ) − − I2 1
Ph COOMe 0 °C Ph COOMe 2
Ph COOMe
81%, dl : meso = 78 : 22
Scheme 27 Oxidative homocoupling of anions formed by an EGB.
in Scheme 27 [120]. The EGB (33)− was derivative of phenyl acetic acid gave selec-
formed ex situ in DMF-Bu4 NClO4 and tively the R,R-dimer [120].
gave much higher yields than when the Deprotonation of carbon acids by O2 −•
reaction was carried out using conven- in the presence of O2 (i.e. when O2 −• is
tional bases with metal counterions [120]. formed in situ by bubbling O2 through
Good yields but lower dl : meso ratios were the catholyte) can lead to oxidative con-
obtained for other aryl groups than for Ph. version of the carbon acid by reaction be-
Nonstoichiometric amounts of I2 could be tween the deprotonated substrate and the
used in combination with anodic regen- excess O2 [107, 121–123], in some cases by
eration. An optically active oxazolidinone consumption of less than stoichiometric
OH
CH3CH(COOEt)2 General conditions:
CH3C(COOEt)2
95%
OH Div. cell
O
MeCN or DMF
PhCH(COOEt)2 + Bu4NBr or Et4NBr
PhC(COOEt)2 Ph C COOEt
7% O2 bubbling
74%
CPE, Ew = −1.0 V
Ph2CHCN Ph2C O
95%
O O
NO2 O 82–86%
Scheme 28 Oxidative conversion of carbon acids initiated by deprotonation by superoxide.

amounts of charge. Examples are given slowly reacting enones, two- or four-fold
in Scheme 28, and more can be found in excess of the carbon acid may be required
Ref. [123]. The product anion, may to some since the ‘‘normal’’ oxidative conversion of
extent, deprotonate the acidic substrate (42) competes with the reaction with the
whereby the reaction becomes partially enone [121].
catalytic. Monoactivated methylene com-
pounds give lower yields, typically 5 to 14.8.8
50% [123, 124]. Condensations
The mechanism by which the hydroper-
oxide intermediate, (42) (Scheme 29) is Despite a very unfavorable proton transfer
converted into the products of Scheme 28 using (35)− as an EGB, condensation of
is not clear. The follow-up reaction of (42) acetophenone with an aromatic aldehyde
may be diverted by reaction with an enone took place within a matter of hours. The
that undergoes epoxidation in 85 to 90% reaction led to α,β-unsaturated ketones,
yield, Scheme 29, [121]. The epoxidation which underwent the Michael addition
reaction does not take place directly from with a second equivalent of deprotonated
O2 and O2 −• but requires the formation ketone, Scheme 30, [80, 81]. The EGB was
of an intermediate of type (42) derived generated ex situ.
either from the enone or from an exter-
nal carbon acid as in Scheme 29. Yields 14.8.9
are considerably improved using an exter- Miscellaneous Reactions
nal carbon acid since the Michael addition
between the enone and its anion other- A very efficient pathway to formation of
wise competes with the epoxidation. For esters by reaction of a carboxylic acid
O O− OH O
O2−• − O2
RCHXY RCXY RCXY RCXY or RCX
−HOO•
(42)
O O
O
90%
Scheme 29 Reaction of deprotonated carbon acids with oxygen.
O H O
DMF, Et 4NOTs Ar1COCH3, Ar2CHO OH
(35H) (35)−
Div. cell, 1F (1 : 1) Ar1 Ar2 −H2O Ar1 Ar2
pK 16.8 pK 24.7
O Ar2 O 1) Ar1COCH3, EGB
2) −H2O
Ar1 Ar1
18–90%
Scheme 30 EGB-initiated aldol condensation between benzaldehyde and acetophenone.

14.9 Base-Catalyzed Reactions 481
with an alkylhalide is by use of (33)− as deprotonation of the carbon acid has to

EGB. Yields were generally between 80 take place. Of the two PBs applied, (29a)
and 100% using a three-step procedure: was superior and both were superior to
formation of the EGB ex situ, addition of NaCH(COOEt)2 as a base (40%) [125].
the acid, and addition of the alkyl halide, Using O2 as the PB (and in the absence of
all reactions carried out in DMF at room diethyl malonate) 2-tosyloxycyclohexanone
temperature [116]. This may be compared gave, after 2 F reduction at the potential
to the simpler two-step procedure [81] in of O2 −• -formation, exclusively methyl cy-
which the carboxylate ions are formed clopentanecarboxylate (75%) when MeI
by direct reduction of the acids followed was added after the electrolysis [126, 127].
by addition of the alkyl halide leading to
somewhat lower yields.
Formation of 1-arylsulfonylcyclobutenes 14.9
via β-elimination from trans 1,2- Base-Catalyzed Reactions
diarylsulfonylcyclobutane takes place in 14.9.1
low yields (<25%) using conventional Michael Additions
bases [72]. Using either O2 or (32) as a PB
in DMF-Et4 NClO4 gave the cyclobutenes Addition of CCl3 − to α,β-unsubstituted
in 50 to 70% yields. Workup was facilitated esters or nitriles, (43), can be carried out
using O2 as the PB [72]. using less than stoichiometric amounts
The detailed mechanism of the Favorskii of (33)− , since the anion formed by
rearrangement in Scheme 31 is not clear. addition is sufficiently basic to deprotonate
Equimolar amounts of the carbon acid CHCl3 [128]. Yields in the range 70 to 80%
and the ketone are used, and initial are obtained when R = H, Me. The acidic
O O HO CH(CO2Et)2
OTs EGB
−
(EtO2C)2CH2 + (EtO2C)2CH +
DMF,
Et4NClO4,
div. cell
pK 16.4 pK >> 16.4 PB = (29a): 76%
PB = (37b): 53%
pK(cyclohexanone) 26.9
Scheme 31 EGB-initiated Favorskii rearrangement.
CHCl3 + (formed ex situ)

O
N
−
R′ R′ CHCl3 R′
DMF
R + CCl3− R − R
EWG −70 °C EWG −CCl3−
EWG
(43) CCl3 CCl3
EWG = COOMe, CN Me
(43a): R = H, R′ = Me, EWG = COOMe From (43a) when
COOMe
(43b): R = R′ = H, EWG = COOMe EGB : CHCl 3 = 1.5 : 1
Cl Cl
Scheme 32 Catalytic vs. stoichiometric amounts of EGB.

HCCl2 COOMe could be used instead of using CH2 =CHX (X = CN, COOEt) as ac-
CHCl3 with similar results [128]. For (43a), ceptors and dialkyl malonates as donors in
cyclization by intramolecular SN 2 reaction DMF-Pr4 NBF4 . The susceptibility of the
competes with protonation, and when stoi- PBs (37a and b) toward the Michael ad-
chiometric amounts of EGB and CHCl3 dition (cf. Sect. 14.8.5) resulted in 60 to
were used, the cyclopropane derivative 93% yield of the addition product when
was the main product, Scheme 32, since subjected to a similar procedure [129].
protonation of the intermediate anion now Superoxide anion formed in situ in a
has to be from (33H), which is less acidic solution exposed to air (i.e. with only
than CHCl3 [128]. a small concentration of O2 ) has been
The trichloromethylation of (43b) has used as an EGB to generate nitroalkane
also been carried out using polyacryl- anions that may add to activated alkenes
amides as PBs [74]. Copolymers of N - or to carbonyl compounds [130, 131]. An
methylacrylamide (57% of the monomer example is shown in Scheme 33. The
reaction is catalytic since the product
units) and styrene (Mn ≈ 4000) gave the
anion can act as a base toward the
best result (94%) using CHCl3 : (43b) =
nitroalkane. Using the nitroalkane as
3 : 1 with addition of the polymeric
the solvent favors the proton transfer
EGB in an amount of reduced N -
pathway over the competing addition of
methylacrylamide units corresponding to
the product anion to a second molecule of
the amount of (43b) (i.e. not a catalytic re-
activated alkene, a pathway that may lead to
action) in DMF. Lower yields (72% and
polymerization [130]. In some cases, better
89%) were obtained with a homopoly- yields of the Michael addition product were
mer of N -methylacrylamide and with a obtained if a stoichiometric amount of the
copolymer of N -methylacrylamide and anion was formed ex situ (with O2 as
N ,N -dimethylacrylamide [74]. the PB), and the activated alkene added
Typical acceptors in Michael additions subsequently [130, 132].
are reducible and their radical anions A catalytic amount (0.001 eq.) of (29a)
often undergo dimerization (hydrodimer- can also be used as the PB for the con-
izations). Either the radical anions or more version in Scheme 33 [122], and a one-pot
likely the dimer dianions can act as EGBs conversion of the addition product (formed
toward the donor in the Michael addition. within 4–22 h) to the corresponding ke-
Since the reaction is catalytic in base when tone could be performed by letting O2 into
the product anion is more basic than the the solution and generating O2 −• . Conver-
donor anion, the Michael addition can sion of the nitro group into the ketone then
take place by reduction of a small frac- took place according to the last reaction in
tion (2–10%) of the acceptor [129]. The Scheme 28 with an overall yield of 46 to
reaction takes place in 20 to 77% yield 62% [122].
O2, Bu4NBr, CCE − EWG NO2 R NO2 NO2

R NO2 − −
Undiv. cell, 0.2 F R NO2
R EWG −R NO2 R EWG
Solvent 80–90%
Scheme 33 Superoxide-catalyzed Michael addition.

Ew = −1.3 V Ew = −1.8 V Ew = −2.3 V

C60 C60−• C602− C603−•
0.05 F 0.03 F 0.03 F
H
O2NCH2COOEt CN CH2(COOEt)2 N
CN (pK 9.2) CN
(pK 16.4) (pK 23)
1 : 100 : 100 : 100
CN CN CN
CN CN
O2N EtOOC N
COOEt COOEt
88% 91% 88%
Scheme 34 Michael additions catalyzed by one-, two- or threefoldly reduced fullerene.
Application of the increasingly basic terephthalaldehyde, this process provides

EGBs formed by the consecutive one- a convenient route to the highly elec-
electron reductions of the fullerene, C60 , tron deficient 1,4-bis(nitroethene) deriva-
is illustrated in Scheme 34 (potentials vs. tive, Scheme 35. This bis(activated alkene)
Fc/Fc+ ) [94]. The reactions in Scheme 34 could be used as the Michael accep-
are catalytic since the addition products are tor in a superoxide anion-initiated re-
less acidic than the carbon acids used, and action with a (strong) carbon acid in
the reactions can therefore be carried out MeCN, cf. Scheme 33. A strong carbon
using very small amounts of the PB. The acid, EtOOCCH2 NO2 (pK 9.2) is required
reactions were carried out in a divided cell for protonation of the addition product
using MeCN/PhMe (2 : 3)-Bu4 NBr. which is also necessary for preventing
polymerization.
14.9.2 For aromatic or heteroaromatic mono-
Reactions Involving Aldehydes and Ketones aldehydes, ArCHO, an efficient procedure
has been developed for synthesis of 1,3-
The procedure described in Sect. 14.9.1 dinitro compounds [132]. Rather than in
for addition of nitroalkane anions to ac- situ reduction of O2 , the O2 reduction
tivated alkenes can also be used for is carried out in a divided cell with the
addition to aldehydes. The nitroalcohol aliphatic nitro compound as the solvent.
formed can be dehydrated in almost Charge corresponding to 0.5 F with re-
quantitative yields in dilute H3 PO4 in a spect to the aldehyde is passed through
subsequent step [130, 131]. Starting with the cell, the current is switched off
CHO
O2, Bu4NBr, 5% aq.
CCE HO NO2 H PO NO2
3 4
+ CH3NO2
Undiv. cell, O N
0.015 F 2 OH O2N
Solvent
CHO 95% 95%
Scheme 35 Superoxide-catalyzed formation of nitroalcohols.

NO2 NO2 −CH NO NO2 NO2

O2, Bu4NBr, CCE ArCHO 2 2
−
CH3NO2 CH2NO2 OH −H O
Div. cell, 0.5 F 2
Solvent
Ar Ar Ar
Ar = ferrocenyl, N-methyl-2-pyrryl 78–95%
Scheme 36 EGB-catalyzed formation of dinitro compounds.
and the aldehyde added. Using these amounts of malonitrile and ethyl ace-
conditions, elimination of water from toacetate to give as final product sub-
the addition compound takes place al- stituted 2-amino-4H -pyranes, Scheme 37,
most quantitatively for aldehydes with an has been reported [135]. The reaction is
electron-donating substituent. Addition of catalyzed by in situ formed O2 −• , and
the second nitronate anion then takes place product formation has been rationalized
giving the 2-aryl-1,3-dinitro compound, as consisting of EGB-catalyzed Knoeve-
Scheme 36 [133]. When Ar = phenyl, 9- nagel condensation of the aldehyde and
anthryl, 2-furyl and 2-thienyl nitroalcohols malonitrile followed by the EGB-catalyzed
were formed together with 30 to 53% Michael addition of the ethyl acetoacetate,
of the 2-aryl-1,3-dinitro compound. Alde- and finally the Thorpe-Ziegler cyclization
hydes with strongly electron withdraw- to give the pyran [135].
A number of electrocatalytic reactions
ing groups (2- or 4-pyridinecarbaldehyde,
have been reported in which the EGB
3-nitrobenzaldehyde or 5-nitro-2-furalde-
is derived by initial reduction of an
hyde) gave only the nitroalcohols [132].
aldehyde or a ketone that at the same
Dehydration of the alcohol is sup-
time functions as the electrophile in a
pressed when the reaction is carried out
coupling reaction [136–139]. It is likely
in DMF-Et4 NOTs containing 1.85 M water that the actual EGB is a dimer dianion
at −40 ◦ C [134]. Under these conditions, of the carbonyl compound or a dianion
aromatic or heteroaromatic aldehydes re- of the carbonyl compound formed by
act with PhCH2 CN, PhCH2 COOEt or disproportionation. The general principle
PhSCH2 CN to give the corresponding al- is outlined in Scheme 38. The reactions
cohols in 52 to 90% yield using 0.04 to become catalytic when the product anion,
0.12 F [134]. It is not clear whether O2 was P− , is protonated by the weak acid,
present in the catholyte or reduction prod- NuH, whereby the nucleophile, Nu− , is
ucts derived from the aldehydes served as regenerated.
the EGB. One example is cathodically induced
A one-pot reaction of aromatic or het- aldol condensation of aliphatic aldehy-
eroaromatic aldehydes with equimolar des, Scheme 39, [138]. In contrast to the
Ar
EtOOC CN
O2, 0.074–0.125 F
ArCHO + CH2(CN)2 + MeCOCH2COOEt 57–88%
MeCN, Bu4NBr
Me O NH2
div. cell, CCE
Ar = Ph, 4-Cl-C6H4, 3-NO2-C6H4, 2-thienyl, 4-pyridinyl
Scheme 37 EGB-catalyzed condensation and subsequent Michael addition.

−•
R1 R1
O + e− O
R2 R2
R1
O R1
EGB R2 NuH
NuH Nu− Nu O− P− PH
2 −Nu−
R
Scheme 38 EGB-catalyzed addition of a nucleophile to a carbonyl compound using the carbonyl
compound as probase.
DMF, Et 4NOTs CHO

RCH2CHO 72–77%
Div. cell, 0.0075–0.02 F
R R
Scheme 39 EGB-catalyzed aldol condensation with the aldehyde as probase.
OH OH
NO2 NO2 NO2 Total yield:
DMF, Et 4NOTs 30–99%
R + R OH
(CH2O)n + R
Div. cell, 0.11–0.50 F
(44) (45) 0–99%

(44) : CH 2O = 1 : 2.2 0–98%
Scheme 40 EGB-catalyzed hydroxymethylation of nitroalkylbenzenes.
noncatalytic mixed condensations of ace- unreduced (44), and the carbanion adds
tophenones with aromatic aldehydes using to CH2 O giving the hydroxymethylated
(35H) as a PB, [81] (Sect. 14.8.8) the reac- product in the anionic form. The chain
tion in Scheme 39 was not followed by a reaction is then sustained by proton trans-
Michael addition. fer from (44) to give the neutral product,
Another example is the electrocatalytic (45). In most cases, the reaction goes on to
reaction between aromatic carbonyl com- give the bis(hydroxymethylated) substrate
pounds and dialkyl phosphonates. Here, as the main product by deprotonation of
rearrangement of the product anion leads (45), Scheme 40, [140].
to a phosphate as the product [136].
Hydroxymethylation of 2- or 4-nitroalkyl- References
benzenes, (44), takes place by passing a 1. K. Uneyama, Top. Curr. Chem. 1987, 142,
catalytic amount of charge through a solu- 167–188.
tion of (44) and (CH2 O)n Scheme 40 [140]. 2. J. H. P. Utley, Top. Curr. Chem. 1987, 142,
(44) is reduced at the electrode and elec- 131–165.
3. J. H. P. Utley, M. F. Nielsen in Organic Elec-
tron transfer from (44)−• to CH2 O is trochemistry (Eds.: H. Lund, O. Ham-
envisaged [140]. The resulting formyl rad- merich), Marcel Dekker, New York, 2001,
ical anion then acts as an EGB toward Chap. 30, pp. 1227–1257.
4. K. Pekmez, H. Özyörük, A. Yildiz, Ber. 28. A. Safavi, N. Iranpoor, L. Fotuhi, Bull.

Bunsen-Ges. Phys. Chem. 1992, 96, Chem. Soc. Jpn. 1995, 68, 2591–2594.
1805–1808. 29. J. Delaunay, A. Lebouc, A. Tallec et al., J.
5. W. C. Barrette, D. T. Sawyer, Anal. Chem. Chem. Soc., Chem. Commun. 1982, 387–388.
1984, 56, 653–657. 30. T. Inokuchi, M. Kusumoto, S. Matsumoto
6. L. C. Portis, J. C. Roberson, C. K. Mann, et al., Chem. Lett. 1991, 2009–2012.
Anal. Chem. 1972, 44, 294–297. 31. T. Inokuchi, S. Takagishi, K. Ogawa et al.,
7. J. P. Billon, J. Electroanal. Chem. 1959, 1, Chem. Lett. 1988, 1347–1350.
486–501. 32. S. Torii, T. Inokuchi, T. Kobayashi, Chem.
8. E. A. Mayeda, L. L. Miller, Tetrahedron 1972, Lett. 1984, 897–898.
28, 3375–3380. 33. S. Torii, T. Inokuchi, S. Takagishi et al.,
9. Y. Pocker, R. F. Buchholz, J. Am. Chem. Soc. Bull. Chem. Soc. Jpn. 1987, 60, 2173–2188.
1970, 92, 2075–2084. 34. T. Fuchigami, K. Yamamoto, H. Yano, J.
10. C. Battistini, P. Crotti, M. Ferretti et al., J. Org. Chem. 1992, 57, 2946–2950.
Org. Chem. 1977, 42, 4067–4071. 35. S. Torii, T. Inokuchi, S. Takagishi et al.,
11. K. Uneyama, N. Nisiyama, S. Torii, Tetrahe- Chem. Lett. 1987, 639–642.
dron Lett. 1984, 25, 4137–4138. 36. J. Zheng, J. L. Gore, G. R. Gray, J. Am.
12. K. Uneyama, A. Isimura, K. Fujii et al., Chem. Soc. 1998, 120, 2684–2685.
Tetrahedron Lett. 1983, 24, 2857–2860. 37. T. Inokuchi, Y. Kurokawa, M. Kusumoto
13. S. Torii, T. Inokuchi, R. Oi, J. Org. Chem. et al., Bull. Chem. Soc. Jpn. 1989, 62,
1982, 47, 47–52. 3739–3741.
14. E. A. Mayeda, L. L. Miller, J. F. Wolf, J. Am. 38. S. Torii, T. Inokuchi, Chem. Lett. 1983,
Chem. Soc. 1972, 94, 6812–6816. 1349–1350.
15. K. Nyberg, J. Chem. Soc., Chem. Commun. 39. S. Torii, T. Inokuchi, K. Kondo et al., Bull.
1969, 774–775. Chem. Soc. Jpn. 1985, 58, 1347–1348.
16. L. Eberson, B. Olofsson, Acta Chem. Scand. 40. N. Gatti, Tetrahedron Lett. 1990, 31,
1969, 23, 2355–2366. 3933–3936.
17. T. Shono, Y. Matsumura, S. Kashimura, J.
41. L. Eberson, L. Jönsson, F. Radner, Acta
Org. Chem. 1983, 48, 3338–3340.
Chem. Scand. 1978, B32, 749–753.
18. Z. Blum, M. Malmberg, K. Nyberg, Acta
42. K. Uneyama, Y. Masatsugu, T. Ueda et al.,
Chem. Scand. 1981, B35, 739–741.
Chem. Lett. 1984, 529–530.
19. S. Torii, H. Tanaka, S. Nakane, Bull. Chem.
43. K. Uneyama, A. Isimura, S. Torii, Bull.
Soc. Jpn. 1982, 55, 1673–1674.
Chem. Soc. Jpn. 1985, 58, 1859–1860.
20. S. Torii, T. Inokuchi, K. Yoritaka, J. Org.
Chem. 1981, 46, 5030–5031. 44. T. Inokuchi, S. Tanigawa, S. Torii, J. Org.
21. T. Shono, Y. Matsumura, T. Hashimoto Chem. 1990, 55, 3958–3961.
et al., J. Am. Chem. Soc. 1975, 97, 45. T. Shono, M. Mitani, J. Am. Chem. Soc.
2546–2548. 1968, 90, 2728–2729.
22. T. Shono, Y. Matsumura, Y. Nakagawa, J. 46. P. E. Iversen, H. Lund, Tetrahedron Lett.
Am. Chem. Soc. 1974, 96, 3532–3536. 1969, 3523–3524.
23. T. Shono, M. Okawa, I. Nishiguchi, J. Am. 47. J. H. Wagenknecht, M. M. Baizer, J. Org.
Chem. Soc. 1975, 97, 6144–6147. Chem. 1966, 31, 3885–3890.
24. P. Gassman, R. Yamaguchi, J. Am. Chem. 48. P. E. Iversen, Tetrahedron Lett. 1971, 55–56.
Soc. 1979, 101, 1308–1310. 49. T. Shono, T. Akazawa, M. Mitani, Tetrahe-
25. M. L. Andersen, M. F. Nielsen, O. Hamm- dron 1973, 29, 817–821.
erich, Acta Chem. Scand. 1997, 51, 94–107. 50. T. Shono, M. Mitani, Tetrahedron Lett. 1969,
26. O. Hammerich, R. M. Henriksen, 687–690.
F. S. Kamounah, Organic Electrochemistry: 51. J. M. Savéant, S. K. Binh, J. Org. Chem.
Manuel L. Baizer Award Symposium in 1977, 42, 1242–1248.
Honor of J. Simonet and J. H. P. Utley, (Eds.: 52. J. M. Savéant, S. K. Binh, Bull. Soc. Chim.
A. Fry, E. Steckhan, Y. Matsumura), 2000, Fr. 1972, 3549–3556.
pp. 9–12. 53. V. L. Pardini, L. Roullier, J. H. P. Utley
27. K. Uneyama, T. Date, S. Torii, J. Org. Chem. et al., J. Chem. Soc., Perkin Trans. 2 1981,
1985, 50, 3160–3163. 1520–1523.
54. A. P. Bettencourt, A. M. Freitas, M. I. 80. T. Fuchigami, A. Konno in Electroorganic

Montenegro et al., J. Chem. Soc., Perkin Synthesis. Festschrift for Manuel M. Baizer
Trans. 2 1998, 515–522. (Eds.: R. D. Little, N. L. Weinberg), Marcel
55. F. G. Bordwell, Pure Appl. Chem. 1977, 49, Dekker, New York, 1991, pp. 387–394.
963–968. 81. T. Fuchigami, T. Awata, T. Nonaka et al.,
56. F. G. Bordwell, Acc. Chem. Res. 1988, 21, Bull. Chem. Soc. Jpn. 1986, 59, 2873–2879.
456–463. 82. M. O. F. Goulart, S. K. Ling-Chung,
57. www.chem.wisc.edu/areas/reich/pkatable/ J. H. P. Utley, Tetrahedron Lett. 1987, 28,
index.htm. 6081–6084.
58. X. M. Zhang, F. G. Bordwell, J. Am. Chem. 83. M. F. Nielsen, S. Spriggs, J. H. P. Utley
Soc. 1994, 116, 968–972. et al., J. Chem. Soc., Chem. Commun. 1994,
59. F. Maran, M. G. Severin, E. Vianello, Tetra- 1395–1397.
hedron Lett. 1990, 31, 7523–7526. 84. L. A. Avaca, J. H. P. Utley, J. Chem. Soc.,
60. F. Maran, D. Celadon, M. G. Severin et al., Perkin Trans. 2 1975, 161–164.
J. Am. Chem. Soc. 1991, 113, 9320–9329. 85. L. A. Avaca, J. H. P. Utley, J. Chem. Soc.,
61. K. G. Boto, F. G. Thomas, Aust. J. Chem. Perkin Trans. 1 1975, 971–974.
1973, 26, 2417–2423. 86. R. R. Mehta, V. L. Pardini, J. H. P. Utley,
62. K. G. Boto, F. G. Thomas, Aust. J. Chem. J. Chem. Soc., Perkin Trans. 1 1982,
1973, 26, 1251–1258. 2921–2926.
63. R. Barhdadi, J. Gal, M. Heintz et al., J. 87. R. C. Hallcher, M. M. Baizer, D. A. White,
Chem. Soc., Chem. Commun. 1992, 50–51. U.S. Patent 4,072,583 (2-7-1978).
64. A. J. Bellamy, I. S. MacKirdy, C. E. Niven, J. 88. CA 1978, 88, 143499.
Chem. Soc., Perkin Trans. 2 1983, 183–185. 89. J. H. P. Utley, S. K. Ling-Chung, Electro-
65. S. Cheng, M. D. Hawley, J. Org. Chem. chim. Acta 1997, 42, 2109–2115.
1985, 50, 3388–3392. 90. T. Fuchigami, K. Suzuki, T. Nonaka, Elec-
66. J. L. Sadler, A. J. Bard, J. Am. Chem. Soc. trochim. Acta 1990, 35, 239–244.
1968, 90, 1979–1989. 91. R. Barhdadi, B. Simsen, M. Troupel et al.,
67. T. Troll, M. M. Baizer, Electrochim. Acta Tetrahedron 1997, 53, 1721–1728.
1975, 20, 33–36. 92. R. Barhdadi, J. Gal, M. Heintz et al., Tetra-
68. R. C. Hallcher, M. M. Baizer, Justus Liebigs hedron 1993, 49, 5091–5098.
Ann. Chem. 1977, 737–746. 93. R. Barhdadi, M. Troupel, J. Périchon, Chem.
69. A. J. Bellamy, G. Howat, I. S. MacKirdy, J. Commun. 1998, 1251–1252.
Chem. Soc., Perkin Trans. 2 1978, 786–793. 94. M. E. Niyazymbetov, D. H. Evans, J. Elec-
70. D. T. Sawyer, R. Y. Komai, Anal. Chem. trochem. Soc. 1995, 142, 2655–2658.
1972, 44, 715–721. 95. A. P. Bettencourt, A. M. Freitas, M. I.
71. E. Laviron, L. Roullier, J. Electroanal. Chem. Montenegro, Tetrahedron Lett. 1999, 40,
1983, 157, 7–18. 4397–4400.
72. J. Delaunay, A. Orliac, J. Simonet, Tetrahe- 96. J. C. Le Menn, J. Sarrazin, Bull. Soc. Chim.
dron Lett. 1995, 36, 2083–2084. Fr. 1988, 781–786.
73. D. Bonafoux, M. Bordeau, C. Biran et al., J. 97. M. E. Niyazymbetov, V. A. Petrosyan, I. Kei-
Organomet. Chem. 1995, 493, 27–32. tel et al., Tetrahedron Lett. 1988, 29,
74. S. Kashimura, Y. Murai, M. Ishifune et al., 3007–3008.
Electrochim. Acta 1997, 42, 2241–2245. 98. V. A. Petrosyan, L. V. Adeavskaya, O. S.
75. D. Bonafoux, M. Bordeau, C. Biran et al., J. Chizhov et al., Russ. Chem. Bull. 1993, 42,
Org. Chem. 1996, 61, 5532–5536. 129–131.
76. D. T. Sawyer, M. J. Gibian, Tetrahedron 99. T. Shono, S. Kashimura, K. Ishizaki et al.,
1979, 35, 1471–1481. Chem. Lett. 1983, 1311–1312.
77. J. Wilshire, D. T. Sawyer, Acc. Chem. Res. 100. T. Shono, M. Ishifune, T. Okada et al., J.
1979, 12, 105–110. Org. Chem. 1991, 56, 2–4.
78. D. T. Sawyer, J. S. Valentine, Acc. Chem. 101. B. Folléas, I. Marek, J. F. Normant et al.,
Res. 1981, 14, 393–400. Tetrahedron Lett. 1998, 39, 2973–2976.
79. D.-H. Chin, G. Chiericato, E. J. Nanni et al., 102. B. Folléas, I. Marek, J. F. Normant et al.,
J. Am. Chem. Soc. 1982, 104, 1296–1299. Tetrahedron 2000, 56, 275–283.
103. T. Shono, S. Kashimura, H. Nogusa, J. Org. 123. M. Sugawara, M. M. Baizer, W. T. Monte

Chem. 1984, 49, 2043–2045. et al., Acta Chem. Scand. 1983, B37,
104. T. Shono, S. Kashimura, M. Sawamura 509–517.
et al., J. Org. Chem. 1988, 53, 907–910. 124. P. M. Allen, U. Hess, C. S. Foote et al.,
105. T. Fuchigami, Y. Nakagawa, J. Org. Chem. Synth. Commun. 1982, 12, 123–129.
1987, 52, 5276–5277. 125. F. De Angelis, M. Feroci, A. Inesi, Bull. Soc.
106. D. Bonafoux, M. Bordeau, C. Biran et al., Chim. Fr. 1993, 130, 712–719.
Synth. Commun. 1998, 28, 93–98. 126. I. Carelli, A. Curulli, A. Inesi et al., J. Chem.
107. M. Sugawara, M. M. Baizer, Tetrahedron Res. (S) 1991, 10–11.
Lett. 1983, 24, 2223–2226. 127. I. Carelli, A. Curulli, A. Inesi et al., J. Chem.
108. L. Kirstenbrügger, P. Mischke, J. Voss et al., Res. (M) 1991, 0183–0190.
Liebigs Ann. Chem. 1980, 461–471. 128. T. Shono, M. Ishifune, O. Ishige et al.,
109. A. J. Bellamy, J. Chem. Soc., Chem. Com- Tetrahedron Lett. 1990, 31, 7181–7184.
mun. 1975, 944–945. 129. M. M. Baizer, J. L. Chruma, D. A. White,
110. C. Degrand, P.-L. Compagnon, F. Gasquez, Tetrahedron Lett. 1973, 5209–5212.
J. Org. Chem. 1982, 47, 4586–4588. 130. C. Suba, M. E. Niyazymbetov, D. H. Evans,
111. C. Degrand, P.-L. Compagnon, F. Gasquez, Electrochim. Acta 1997, 42, 2247–2255.
J. Chem. Soc., Chem. Commun. 1983, 131. Z. Niazimbetova, S. E. Treimer, D. H.
383–384. Evans et al., J. Electrochem. Soc. 1998, 145,
112. C. Degrand, G. Belot, P.-L. Compagnon 2768–2774.
et al., Can. J. Chem. 1983, 61, 2581–2589. 132. Z. I. Niazimbetova, D. H. Evans, L. M.
113. R. C. Hallcher, D. A. White, M. M. Baizer, Liable-Sands et al., J. Electrochem. Soc. 2000,
J. Electrochem. Soc. 1979, 126, 404–407. 147, 256–259.
114. M. Feroci, A. Inesi, L. Rossi, Tetrahedron 133. Z. I. Niazimbetova, D. H. Evans, I. A.
Lett. 2000, 41, 963–966. Guzei et al., J. Electrochem. Soc. 1999, 146,
115. M. A. Casadei, S. Cesa, A. Inesi, Tetrahe- 1492–1495.
dron 1995, 51, 5891–5900. 134. S. Torii, H. Kawafuchi, T. Inokuchi, Bull.
116. T. Shono, O. Ishige, H. Uyama et al., J. Org. Chem. Soc. Jpn. 1990, 63, 2430–2432.
Chem. 1986, 51, 546–549. 135. A. M. Shestopalov, Z. I. Niazimbetova,
117. V. A. Petrosyan, A. A. Vasilev, V. I. Tata- D. H. Evans et al., Heterocycles 1999, 51,
rinova, Russ. Chem. Bull. 1994, 43, 84–88. 1101–1107.
118. S. T. Nugent, M. M. Baizer, R. D. Little, 136. M. Kimura, T. Kurata, T. Yamashita et al.,
Tetrahedron Lett. 1982, 23, 1339–1342. Electrochim. Acta 1997, 42, 2225–2231.
119. M. A. Casadei, S. Cesa, A. Inesi et al., New 137. J. C. Gard, B. Hanquet, L. Roullier et al.,
J. Chem. 1994, 18, 915–921. Can. J. Chem. 1996, 74, 55–63.
120. Y. Matsumura, M. Nishimura, M. Wata- 138. T. Shono, S. Kashimura, K. Ishizaki, Elec-
nabe et al., Electrochim. Acta 1997, 42, trochim. Acta 1984, 29, 603–605.
2233–2239. 139. E. M. Abbott, A. J. Bellamy, J. B. Kerr et al.,
121. M. Sugawara, M. M. Baizer, J. Org. Chem. J. Chem. Soc., Perkin Trans. 2 1982,
1983, 48, 4931–4934. 425–430.
122. W. T. Monte, M. M. Baizer, R. D. Little, J. 140. S. Torii, Y. Murakami, H. Tanaka et al., J.
Org. Chem. 1983, 48, 803–806. Org. Chem. 1986, 51, 3143–3147.
489
15
Indirect Electrochemical
Reactions
Sigeru Torii
Institute of Creative Chemistry, Okayama, Japan
15.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491
15.2 Indirect Electrooxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493

15.2.1 Indirect Oxidation with Halide Ions . . . . . . . . . . . . . . . . . . . . . . 493
15.2.1.1 Chloro Cation [CI]+ -assisted Indirect Oxidation . . . . . . . . . . . . . . 493
15.2.1.2 Bromo Cation [Br]+ -assisted Indirect Oxidation . . . . . . . . . . . . . . 495
15.2.1.3 Indirect Oxidation with [I]+ and IO4 − as Electron Carriers . . . . . . . 500
15.2.2 Indirect Oxidation with Organic Mediators . . . . . . . . . . . . . . . . . . 502
15.2.2.1 Mediators Containing Sulfur and Selenium Elements . . . . . . . . . . 503
15.2.2.2 Mediators Containing Nitrogen . . . . . . . . . . . . . . . . . . . . . . . . . 503
15.2.3 Indirect Oxidation with Other Redox Systems . . . . . . . . . . . . . . . . 508
15.2.4 Metal Ion-assisted Indirect Oxidation . . . . . . . . . . . . . . . . . . . . . 509
15.2.4.1 Indirect Oxidation with Metal Ion Redox Systems . . . . . . . . . . . . . 509
15.2.4.2 Indirect Oxidation with Nickel (Ni) and Cobalt (Co) Compounds . . . 509
15.2.4.3 Iron (Fe) Complex-assisted Oxidation . . . . . . . . . . . . . . . . . . . . . 510
15.2.4.4 Indirect Oxidation with Chromic Acid [Cr(VI)] . . . . . . . . . . . . . . . 512
15.2.4.5 Palladium (Pd)-assisted Oxidation . . . . . . . . . . . . . . . . . . . . . . . 513
15.2.4.6 Ruthenium (Ru)-assisted Oxidation . . . . . . . . . . . . . . . . . . . . . . 517
15.2.4.7 Osmium (Os)-assisted Oxidation . . . . . . . . . . . . . . . . . . . . . . . . 519
15.2.4.8 Indirect Oxidation with Manganese [Mn(III)] . . . . . . . . . . . . . . . . 520
15.2.4.9 Indirect Oxidation with Cerium (Ce) Complexes . . . . . . . . . . . . . . 525
15.2.4.10 Copper (Cu) and Silver (Ag)-assisted Oxidation . . . . . . . . . . . . . . . 530
15.2.4.11 Thallic Ion [Tl(III)]-assisted Oxidation . . . . . . . . . . . . . . . . . . . . . 532
15.3 Indirect Electroreduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 532

15.3.1 Indirect Reduction with Mediators Containing Nickel, Cobalt, and Iron 533
15.3.1.1 Nickel (Ni) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . . . . 533
15.3.1.2 Cobalt (Co) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . . . . 548
15.3.1.3 Iron (Fe) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . . . . . . 554
490 15 Indirect Electrochemical Reactions
15.3.2 Indirect Reduction with Mediators Containing Palladium, Rhodium,

Iridium, and Platinum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
15.3.2.1 Palladium (Pd) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . . 559
15.3.2.2 Platinum (Pt) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . . . 563
15.3.2.3 Rhodium and Iridium Complex Mediators . . . . . . . . . . . . . . . . . . 563
15.3.3 Indirect Reduction with Mediators Containing Ruthenium and
Osmium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 566
15.3.3.1 Ruthenium (Ru) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . 566
15.3.3.2 Osmium (Os) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . . 568
15.3.4 Indirect Reduction with Mediators Containing Chromium,
Molybdenum, and Tungsten . . . . . . . . . . . . . . . . . . . . . . . . . . . 569
15.3.4.1 Chromium (Cr) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . 569
15.3.4.2 Molybdenum (Mo) Complex Mediators . . . . . . . . . . . . . . . . . . . . 571
15.3.4.3 Tungsten (W) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . . 573
15.3.5 Indirect Reduction with Mediators Containing Manganese and
Rhenium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 574
15.3.5.1 Manganese (Mn) Complex Mediators . . . . . . . . . . . . . . . . . . . . . 574
15.3.5.2 Rhenium (Re) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . . 576
15.3.6 Indirect Reduction with Mediators Containing Titanium, Tin, and
Lead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 577
15.3.6.1 Titanium (Ti) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . . . 577
15.3.6.2 Tin (Sn) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . . . . . . 579
15.3.6.3 Lead (Pb) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . . . . . 580
15.3.7 Indirect Reduction with Mediators Containing Zinc (Zn), Mercury
(Hg), and Cadmium (Cd) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 581
15.3.8 Indirect Reduction with Mediators Containing Selenides (Se) or
Tellurides (Te) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 586
15.3.9 Indirect Reduction with Mediators Containing Miscellaneous Metal
Complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 588
15.3.9.1 Samarium (Sm) and Indium (In) Complex Mediators . . . . . . . . . . 588
15.3.9.2 Antimony (Sb) and Bismuth (Bi) Complex Mediators . . . . . . . . . . . 590
15.3.9.3 Copper (Cu) Complex Mediators . . . . . . . . . . . . . . . . . . . . . . . . 591
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 591
491
15.1 an ‘‘indirect electrochemical reaction’’. For

Introduction example, the oxidation consists of two well-
defined processes: (1) electrooxidation of
Indirect electrochemical methods have the mediator to a higher oxidation state;
been intensively studied, especially from (2) chemical oxidation of the organic sub-
the viewpoint of development of inno- strate with the mediator. The technique in
vative synthetic methods in industrial which these two processes are carried out
organic chemistry. The indirect procedure together in a single electrolysis is called the
is required when the direct method is un- ‘‘in-cell method,’’ while the process involv-
suitable because (1) the desired reaction ing separated electrochemical and chem-
does not proceed sufficiently because of ical steps is called the ‘‘ex-cell method.’’
an extremely slow reaction or a very low Generally, redox electron carriers include
current efficiency; (2) the electrolysis lacks a variety of metals, nonmetals, and or-
product-selectivity and thus offers only a ganic redox systems. For example, the
low yield; (3) tar and products cover the indirect oxidation of toluene using Mn(III)
surface of the electrode, interrupting the gives a quantitative yield of benzaldehyde.
electrolysis. Indirect electrochemical tech- Mn(III) can be regenerated through elec-
niques involve the recycling of mediators trolysis of the Mn(III) species [25]. The
(or electron carriers) in a redox system, as direct oxidation of toluene produces ben-
depicted in Fig. 1 [1–24]. zaldehyde together with many by-products.
The redox electron carrier produced at The flow diagram for benzaldehyde pro-
the electrode can react homogeneously duction from toluene (in-cell method) by
with organic substrates that may be dis- indirect electrolysis is presented in Fig. 2.
solved, suspended, or emulsified, to pro- A schematic layout of an indirect ex-cell
vide the desired oxidized (or reduced) method is shown in Fig. 3 [1]. A large-
products as well as the regenerated redox scale preparation of anisaldehyde from
electron carrier. The cycle is completed p-methoxytoluene illustrates this idea. The
when the reduced (or oxidized) electron ex-cell method can also be used for the
carrier is reoxidized (or rereduced) at the manufacture of anthraquinone from an-
anode (or cathode) to regenerate the origi- thracene [1]. The process involves a two-
nal oxidizing (or reducing) redox electron step reaction. The reaction conditions for
carrier. The recycling of a suitable redox the first step must permit a sufficiently
electron carrier in this way is referred to as fast electrochemical reaction of the carrier.
Indirect electroreactions
Starting
material Product
Electron carrier Electron carrier

active for oxidation active for reduction
(or reduction) (or oxidation)
Electrodes
Fig. 1 Recycling of a mediator (electron carrier) for indirect
electroreaction.
Distillation
CH3 CHO
Oil–water separation
Electrolysis
Mn2+ Mn3+
Fig. 2 Indirect electrooxidation of toluene by an in-cell method.
Additionally, the rate of the homogeneous from a highly acidic media after the
reaction of the carrier with the substrate electrolysis [3]. The selection of electrode
must be considered. materials is also very important. In most
Also important is the choice of a cases, lead is used as the electrode
suitable redox system for the indirect material for both the anode and the
electroreaction of particular substrates. For cathode. An improvement in its corrosion
instance, toluene can be oxidized with resistance [26] as well as in its overvoltage
Mn(III) or Ce(IV) to benzaldehyde, whilst characteristic has been made by alloying
with Cr(VI) benzoic acid is obtained. it with a small amount of a second
On the other hand, anthraquinone is metal such as silver or antimony [27].
commercially prepared from anthracene Lead dioxide-coated carbon or graphite
by employing chromic acid oxidation. electrodes can be used as anodes. In place
The feasibility of the indirect redox of platinum electrodes, platinum-coated
process strongly depends on whether titanium electrodes are used in some
the product can be readily separated cases [28].
15.2 Indirect Electrooxidation 493
MeO Me Reaction
Ce3+
MeO CHO Oil–water

Ce4+
separation
Ce3+
Electrolysis
Ce3+ Ce4+
Fig. 3 Electrooxidation of p-methoxytoluene with cerium salt by an ex-cell method.
As mentioned above, the critical feature systems under basic and acidic conditions
of indirect electrochemical reactions is the are listed in Table 1 [31]. The combination
correct choice of a redox system. Specific of these redox systems with a suitable sub-
examples of indirect electrochemical reac- strate has been shown to be extremely ef-
tions with a great variety of redox carriers fective in organic synthesis. Thus, by con-
are presented in the following sections. sidering such novel combinations, there
are numerous possibilities of finding new
types of electrosynthetic reactions.
15.2
Indirect Electrooxidation 15.2.1.1 Chloro Cation [CI]+ -assisted
Indirect Oxidation
15.2.1 The combination of the electrogenerated
Indirect Oxidation with Halide Ions chloro cation [CI]+ with diphenyldise-
lenide is a typical example of the func-
Nonmetal oxidizing redox systems that in- tionalization of an olefin. The electro-
volve halide ions and organic compounds chemical oxyselenation-deselenation of (1)
as electron carriers play an extremely to (2) proceeds in an MeOH-NaCl-(Pt)
important role for functionalization of or- system (Scheme 1) [32]. The bromide salt-
ganic molecules. promoted oxyselenation of olefins is dis-
Halide ions, in general, are typical cussed in Sect. 15.2.2. Penicillin (3) can be
nonmetal type electron carriers. The fol- converted into the oxazoline-azetidinone
lowing halogen redox systems for indi- (4) by a chloride salt-promoted paired re-
rect electrooxidation are well established; action in an MeOH-t-BuOH(5 : 1)-MgCl2 -
Cl− /[Cl]+ , Br− /[Br]+ , Br− /BrO− , I− /[I]+ , (Pt) system at −40 ◦ C in 74∼93%
IO3 − /IO4 − , and so on [29, 30]. The yield (Scheme 2) [33, 34]. This conversion
oxidation potentials (E ◦ ) of halogen redox probably involves an initial attack of an
Tab. 1 Electrode reactions of X− and their redox potentials(E◦ ) in basic and acidic solutions
Electrode reaction under basic conditions E◦ Electrode reaction under acidic conditions E◦
−2e− −2e−
Cl− + 2OH− −−−→ ClO− + H2 O 0.89 Cl− (2Cl)− −−−→ [Cl]+ (Cl2 ) 1.39
−2e− −e−
ClO− + 2OH− −−−→ ClO2 − + H2 O 0.66 1/2Cl2 + H2 O −−−→ HClO + H+ 1.59
−2e− −2e−
ClO2 − + 2OH− −−−→ ClO3 − + H2 O 0.33 HClO + H2 O −−−→ HClO2 + 2H+ 1.64
−2e− −2e−
ClO3 − + 2OH− −−−→ ClO4 − + H2 O 0.36 HClO2 + H2 O −−−→ ClO3 − + 3H+ 1.21
−2e−
ClO3 − + H2 O −−−→ ClO4 − + 2H+ 1.19
−2e− −2e−
Br− + 2OH− −−−→ BrO− + H2 O 0.76 Br− (2Br− ) −−−→ [Br] + (Br2 ) 1.087
−2e− −5e−
Br− + 6OH− −−−→ BrO3 − + 3H2 O 0.61 1/2Br2 + 3H2 O −−−→ BrO3 − + 6H+ 1.52
−2e− −5e−
I− (2I− ) −−−→ [I] + (I2 ) 0.536 1/2I2 + 3H2 O −−−→ IO3 + 6H+ 1.195
−2e− −e−
3I− −−−→ I3 − 0.536 1/2I2 + H2 O −−−→ HlO + H+ 1.45
−2e−
I− + 2OH− −−−→ lO− + H2 O 0.49
E◦ : Standard redox potential (25 ◦ C).
(PhSe)2 + MeOH
SO2Ph SO2Ph
MeO
(1) [Cl] + Cl − (2) 81% yield
−2e−
Anode
Scheme 1 Electrochemical oxyselenation-deselenation.
activated chlorine atom on divalent sul- nitriles, has been performed by ox-
fur, giving an intermediate (5), which may idation with electrogenerated reactive-
suffer an intramolecular nucleophilic at- halogen species (e.g. [Cl+ ] and [Br+ ]) [35].
tack of the amide group at the C(7) position Indirect electrooxidation using sodium
to produce the oxazoline ring compound chloride as a redox catalyst is equally ef-
(6). Subsequent reaction with the base pro- fective for α-methoxylation of dipeptide
duced at the cathode gives (4). esters. Application for the synthesis of
Oxidative cleavage of the C(1)−C(2) chiral heterocyclic compounds along with
bond of aziridines and 2-amino-1-cycloal- their usage as synthetic building blocks
kanols, giving the corresponding keto has been investigated [36].
R1
R1CONH N O
S
MeOH-t-BuOH-MgCl2-(Pt)
N 74∼93% yields N
O O
(3) COOR2
(4) COOR2
+
[Cl]
ROH
− +e− RO −
−e H2
Cl −
Anode Cathode
R1 R1
Cl
O N O
H N S+
SCl
N
N O
O
COOR2 COOR2
(5) (6)
Scheme 2 Conversion of penicillin into a oxazoline-azetidinone.
Aldoximes (7) are converted into the bromide as mediator, leads to the corre-
corresponding nitriles (8) by using halogen sponding α-keto carbonyl compounds (10)
ions as mediators (Scheme 3). Sodium in good yields (Scheme 4) [40]. Hemiac-
chloride affords the best result among etals formed in situ from aldehydes (11) can
the supporting electrolytes (Cl− > Br− > be oxidized indirectly to the correspond-
I− > ClO4 − > TsO− ) [37]. ing esters (12) (Scheme 5) [41]. Electro-
Hypervalent iodobenzene chlorofluo- chemical deacetylation of 3-oxobutanoate
rides, a useful fluorinating reagent, has derivatives leads to substituted esters [42].
been used for indirect anodic gem- The reaction is initiated by the bromi-
difluorination [38, 39]. nation of the active methylene group by
an electrogenerated bromonium ion fol-
15.2.1.2 Bromo Cation [Br]+ -assisted lowed by base-catalyzed deacetylation, and
Indirect Oxidation terminated by reductive dehalogenation
The conversion of α-hydroxylketones of the α-bromo carbonyl compound at
and aliphatic α-hydroxyl esters (9), with the cathode.
MeOH-NaCl-(Pt)
R C N OH R C N O R C N
H
(7) (8) 40∼91% yields
Scheme 3 Conversion of aldoximes into nitriles.
OH O
CH2Cl2/H2O-NaBr-(Pt/Pt)
Ar CH CO2Me Ar C CO2Me
70∼95% yields
(9) (10)
Scheme 4 Conversion of α-hydroxyesters into α-ketoesters.

R MeOH-KBr-(Pt/C)
C O + R′ OH R CO2 R′
H 69∼100% yields
(11) (12)
Scheme 5 Conversion of aldehydes into esters.
The conversion of glucose (14) bond in an aq. MeCN-Bu4 NBF4 -(Pt) sys-
into both sorbitol (13) and gluconic tem [48].
acid (15) has been realized in an The combination of the electrogener-
aq. NaBr/CaCO3 /Na2 SO4 -(C/Pb) system ated bromo cation [Br]+ with diphenyl-
(Scheme 6) [43, 44]. O-Glycosylation of disulfide is a typical example of het-
thioglycosides with alcohol is successfully ero–hetero bonds.
performed by electrooxidation, in the The direct electrosynthesis of S−N
presence of catalytic amounts of bonds from disulfides and amines has
ammonium or alkali bromide, to afford been shown to occur through a reaction
O-glycosides [45]. In a similar way, [Br]+• - of the amine with the oxidized disulfide
assisted electrochemical N -glycosylation being a strong electrophile. In contrast
of silylated pyrimidines with protected to the results, the cross-coupling of
arylthioriboses has been attained [46]. phthalimide (16) with disulfide does not
Pyrimidine bases and their nucleosides proceed in a direct electrolysis. However,
have been indirectly brominated, in the electrosynthesis of sulfenimides (17)
chlorinated, and iodinated to their 5- can be achieved by a [Br]+ -mediated
bromo(or halo) derivatives [47]. cross-coupling reaction of imides with
Deprotection of thioesters under neutral disulfides (Scheme 7). The electrolysis of a
conditions has been achieved by elec- mixture of (16) and dicyclohexyl disulfide
trooxidative cleavage of the carbon–sulfur in an MeCN-NaBr-(Pt) system affords
−2e−
HO HO Br+ Br- HO
HO OH HO O HO OH
HO HO HO O
Cathode HO Anode HO Ca
HO OH O
OH 2
(13) Sorbitol (14) Glucose (15) Calcium gluconate
Total current efficiency: 135 %
Scheme 6 Simultaneous oxidation of glucose to gluconic acid and reduction to sorbitol.
O O
MeCN-NaBr-(Pt)
NH N S R
R-S-S-R
O O
(16) 93∼99% yields (17)
Scheme 7 Br+ -mediated cross coupling to form S−N bonds.

the corresponding (17) (R = cyclohexyl) in Electrochemical epoxidation of olefins

quantitative yield [49]. has been developed for the production of
The direct electrosynthesis of sulfen- ethylene and propylene oxides in aque-
imines (19) from α-aminoalkanoates (18) ous sodium chloride or bromide solution.
and diaryl disulfides proceeds in a CH2 Cl2 - However, associated with these electrol-
H2 O-MgBr2 -(Pt) system in 70∼96% yields yses are difficulties in achieving product
(Scheme 8) [50]. Electrolysis of sulfenami- selectivity as well as in obtaining high
des (20) is considered to be the intermedi- yields of the epoxides. Recently, a regiose-
ates in the direct conversion of (18)→(19). lective ω-epoxidation of polyisoprenoids
The P−S bond formation of dialkyl (23) to (24), promoted by electrooxida-
(or diaryl) phosphites (21) with disulfide tion in an MeCN/THF/H2 O-NaBr-(Pt) sys-
proceeds in an MeCN-NaBr/Et4 NClO4 - tem, has been achieved (Scheme 10) [52].
(Pt) system at 20∼25 ◦ C, giving phos- The electrochemical conversion of (21)
phorothiolates (22) in 72∼91% yields (R = CH2 SO2 Ph) to (22) (88% yield) is
(Scheme 9) [51]. In this reaction, both superior to the NBS method (69%) or to m-
sodium iodide and sodium chloride are CPBA oxidation (72%). Other bromides are
less effective than sodium bromide. De- also effective for epoxidation in the follow-
pending on the nature of the cation, the ing order: NaBr (91%) > Et4 NBr (82%) >
yields of (22) decrease in the order of KBr (78%) > LiBr (75%) > NH4 Br (13%).
Na+ (91%) > K+ (76%) > Li+ (69%) > The utility of the method is exempli-
Et4 N+ (46%). fied by the facile syntheses of dl-iron [53]
N SAr
NH2
CH2Cl2/H2O-MgBr2 -(Pt)
R CO2R′ R CO2R′
79~93% yields
(18) (19)
HN SAr CH2Cl2/H2O-MgBr2 -(Pt)
R CO2R′ 70~96% yields
(20)
Scheme 8 Sulfenimines from α-aminoalkanoates.
RO MeCN-NaBr-Et 4NClO4(Pt) RO
P(O)H P(O) S R′
+ R′S-R′S
RO RO
(21) (22)
Scheme 9 Phosphorothiolates from dialkyl- and diaryl phosphites.
MeCN/THF/H2O-NaBr-(Pt)
R R
O
(23) [Br] + Br −
(24)
−
−2e
Anode
Scheme 10 Regioselective ω-epoxidation of polyisoprenoids.

and piperonal [54]. The use of polymeric (27, 28, 29, and 30) are presented below.
quaternary ammonium bromide as a pre- The electrochemical hydroxyselenation
cursor of a polymeric reagent for elec- proceeds readily in an MeCN-H2 O(3 : 1)-
troepoxidation of olefins has been recently NaBr-(Pt) system. A similar method is
reported [55]. employed in the conversion of various
Oxyselenation is a powerful tool for func- olean-12-ene sapogenols into olean-11-
tionalization in synthetic organic chem- en-28,13b-olides [56]. One-step conversion
istry. Electrochemically generated [Br]+ of olefins (31) into allylic alcohols (32)
or bromine reacts with (PhSe)2 , produc- (R = H) and ethers (32) (R = alkyl) can
ing PhSeBr. Attack of PhSeBr on the also be performed by an electrooxidative
olefin (25) gives a selenated intermedi- oxyselenation-deselenation sequence via
ate followed by solvolysis to provide (26) (33)→(34) (Scheme 12) [57, 58]. The re-
and a bromide ion (Scheme 11). A typical action proceeds preferentially in an ROH-
electrolysis is carried out in a MeOH- Et4 NBr-(PhSe)2 -(Pt) system without using
Et4 NBr/H2 SO4 (trace)/(PhSe)2 -(Pt) sys- sulfuric acid. In this manner, dl-rose oxide
tem in an undivided cell. Some results (37) can be prepared from citronellol (35)
(PhSe)2 + ROH
R′
R′
RO SePh
[Br] + Br −
(25) (26)
−2e−
R = Me, Et, Ac, H Anode
OR
(27) R = Me 96% OH
H 96%
RO
SePh Ac 98%
SePh (28) R = Me 90%
H 91%
OH
RO SePh
(29) R = Me 83% RO OH (30) R = Me 91%
SePh
H 80% H 93%
Scheme 11 Oxyselenation of alkenes.
ROH-Et 4NBr-(Pt)
R′ 72∼95% yields R′
OR
(31) (32)
(PhSe)2
PhSeOH
R′ −2e− R′
RO RO
SePh SePh
(33) (34)
O
Scheme 12 Oxyselenation-deselenation of alkenes to allyl alcohols.

by electrochemical allyloxylation via oxy- ion is the least. Magnesium ion seems
selenation followed by a demethoxyla- to be essential for promoting enolization
tive cyclization of (36) by treatment (40→41). The method can also be applied
with BF3 -etherate in 85% overall yield to alicyclic systems.
(Scheme 13a). Similarly, a one-step syn- Benzyl alcohol can be smoothly con-
thesis of dl-dihydroactinidiolide (39) can be verted to benzaldehyde by electrochemi-
performed by electrochemical intramole- cally recycled BrO− as an oxidizing catalyst
cular oxyselenation-deselenation of (38) in an emulsion system prepared from a
(Scheme 13b). α-Phenylselenoketones are mixture of water, amyl acetate, and 2%
valuable precursors to α, β-unsaturated Bu4 NHSO4 [60]. A different hypobromite
and α-exo-methylene carbonyl com- reagent is provided by an electrochem-
pounds. A facile access to α-phenylselenyl ical oxidation of a cross-linked poly-4-
carbonyl compounds (41) by electrooxida- vinylpyridine in an MeCN-H2 O-HBr-(Pt)
tion of the ketone (40) is available in an system [61]. Secondary alcohols can be ox-
MeCN(or AcOH)-MgBr2 /(PhSe)2 -Et4 NBr- idized by this method to give ketones
(Pt) system (Scheme 14) [59]. The effect of in high yields. The electrooxidation of
halide ions is remarkable. The bromide N -monoalkyltosylamides (42) in a two-
ion is the most effective and the iodide phase system consisting of cyclohexane
MeOH-Et4NBr-(Pt) BF3 • Et2O

OH OH O
(PhSe)2 94% yield H
89% yield
(a) OMe
(35) (36) (37)
O
CO2H CH2Cl2-Et 4NBr-(Pt)
(PhSe)2 O
(b) (38) 73% yield (39)
Scheme 13 Cyclic ethers and lactones by allyloxylation-cyclization of unsaturated alcohols and
carboxylic acids.
Electrogenerated
OH O
R′ PhSeBr
R′
R R
(40) Br − (41) SePh
Scheme 14 α-Phenylselenyl carbonyl compounds from ketones.
NHTs
NHTs MeOH-MeONa-KBr-(Pt) OMe
R R
R′ 74∼96% yields OMe
(42) (43)
Scheme 15 Conversion of alkyltosylamides into α-tosylamino aldehyde acetals.

and water containing KOH and KBr un- electrooxidation in an MeOH-NaI-(C/Pt)

der heating yields pyrrolidine derivatives system in an undivided cell [64–66].
in 52∼100% yields [62]. Employing dif- The iodine-assisted methoxylation would
ferent oxidation conditions such as the take place in the following way:
MeOH-MeONa/KBr-(Pt) system results (1) initial iodination by the reaction
for (42) in α-(tosylamino) aldehyde acetals of electrogenerated iodine yields α-
(43) in 74∼96% yields (Scheme 15) [62]. iodocycloketone that undergoes a second
iodination to give diiodocycloketone;
15.2.1.3 Indirect Oxidation with [I]+ and (2) the substitution of the iodo group by
IO4 − as Electron Carriers electrogenerated methoxyl anion affords
The transformation of aldehydes (44) the dimethoxide. The conversion of alkyl
(R3 = H) and ketones (44) (R3 = Alkyl) to aryl ketones to methyl α-arylalkanoates
the corresponding α-hydroxylated acetals is achieved in a TMOF(trimethyl
(45) has been performed in an MeOH- orthoformate)-LiClO4 /I2 -(Pt) system. Use
KOH/KI-(Pt/C) system. The first step of of a commutator is essential to suppress
the oxidation is considered to proceed the deposition of nonconducting materials
by the attack of an electrogenerated on the surface of the cathode [67].
active iodine species [I]+ to an Oxiranes (47) and (48) are produced
enolized carbonyl group (Scheme 16) [63]. in fairly good yields when ketones are
The electrochemical dimethoxylation of electrooxidized in an MeOH-NaCN/KI-
cyclic ketones proceeds by indirect (Pt) system (Scheme 17) [68]. In an
R2 R2 OMe
R3 MeOH-KOH/KI-(Pt/C)
R1 R1 R3
[I] + OH OMe
O I−
(44) −2e− (45) 52∼84% yields
Anode
Scheme 16 Transformation of aldehydes and ketones to α-hydroxy acetals.
R2 R2 R2
R3 MeOH-NaCN/KI-(Pt) R3 R3
R1 R1 + R1
O O C
O CN NH
[I] + I−
(46) −2e− (47) (48)
OMe
Anode (47) + (48) = 47∼83% yields
Scheme 17 Oxiranes from ketones.
R1 R1 R1 N R2
O NH MeOH-NH3/KI-(Pt)
R2 R2 R2 N R1
(49) (50) H
[I] + I−
(51) 55∼76% yields
−2e−
Anode
Scheme 18 2,2-Dihydro-1H-imidazoles from ketones.

ammonia-methanol solution, ketones (49) electrooxidation of D-glucitol 1,3,4,6-diace-

can be transformed into the corresponding tals can lead to 2-keto-L-gluconic acid
2,5-dihydro-1H-imidazoles derivatives (51) 3,5,4,6-diacetals by using sodium iodide
via imines (50). The electrolysis is carried as a mediator [72].
out in an MeOH-MeONa/NH3 /KI-(Pt) The Ritter reaction [6] proceeds by the
system (Scheme 18) [69]. electrooxidation of alkyl iodides (56) in
Ring construction of pyrrolidinoenami- an MeCN-(Pt) system to form N -alkyl
nes (52) of alicyclic ketones, giving the acetamides (58) (Scheme 21). Attack of
bicyclo compound (53), has been attained carbenium ion intermediate – from disso-
by using the iodide ion as a mediator in an ciation of the initially formed alkyl cation
MeOH-NaCN-(Pt) electrolysis system [70] radical – to acetonitrile would give the
(Scheme 19). iminium cation (57). However, a differ-
Oxidation of alcohols (54) with the iodo ent mechanism is proposed, whereby the
cation [I]+ as an electron carrier yields alkyl iodide reacts with the electrogener-
ketones (55) in 52∼84% yields in an ated iodo cation [I]+ [73].
aqueous (t-BuOH)-KI-(C or Pt) system in Formation of N ,N -dialkylformamides
an undivided cell (Scheme 20) [71]. The occurs successfully by electrolysis of a mix-
electrogenerated iodo cation is considered ture of sec-amines and formaldehyde in
to behave as an oxidizing agent. Indirect an aqueous KI-(Pt/C) system in 57∼93%
NC N
N
MeOH-NaCN/KI-(Pt/C)
n n−1
[I] + I−
(52) −2e− (53)
49∼63% yields
Anode
Scheme 19 Cyclopropanation of enamines.
R1 H2O/t-BuOH-KI-(C or Pt) R1
CH OH C O
R2 R2
[I]+ I−
(54) (55)
−2e−
52∼84% yields
Anode
Scheme 20 Iodide-mediated oxidation of alcohols.
MeOH-KOH/KI-(Pt/C) + H2O
R I R N C Me R NHCOMe
[I]+ −
I
(56) (57) (58)
−2e−
Anode R (%) = 2-Octyl (54);
Cyclohexyl (45);
1-Adamantyl (60)
Scheme 21 Conversion of alkyl iodides into acetamides.

yields. In this system, the electrooxi- be produced readily by oxidative cleav-

dation of I− probably provides an ac- age of a vicinal diol of starch (62) with
tive [I]+ species that associates with the periodic acid regenerated by electroly-
lone-pair electron on the nitrogen atom. sis (Scheme 23) [78]. 2,3-Butanediol can
Electrooxidation of enamines in similar be cleaved anodically by using a peri-
conditions affords the corresponding β- odate/iodate redox mediatory system to
keto amines in 31∼60% yields [74]. Iodo give acetoaldehyde [79]. The electrolytic
cation [I]+ -assisted electrooxidative prepa- conversion of iodic acid to periodic acid
ration of nitrones has been performed occurs in a 5% H2 SO4 -(PbO2 -Pb) system
in an MeOH-NaI-(Pt) system in good at pH 0.7∼2.0 at 7% iodic acid concen-
yields [75]. tration. The transformation of (62) to (63)
Formation of the P−N bond has by electro-regenerated periodic acid pro-
been observed when the cross-coupling ceeds in more than 90% conversion yields.
of dialkylphosphites (59) with amines The cleavage of electron-rich double bonds
(60) proceeds by an iodo cation [I]+ - of (64) to the corresponding aldehydes
promoted electrooxidation, affording N - (65) using a ruthenium-silicon-tungstate
substituted dialkylphosphor-amidates (61) [(Bu4 N)5 (H2 O)RuSiW11 O39 ] and IO4 − /
(Scheme 22) [76]. Lack of alkali iodide in IO3 − double redox system has been devel-
the electrolysis media results in the for- oped. The electrolysis of aryl substituted
mation of only a trace of (61), indicating olefins yields the corresponding aldehydes
that the iodide plays an important role in in 59∼79% yields (Scheme 24) [80].
the P−N bond-forming reaction. In con-
trast, usage of sodium bromide or sodium 15.2.2
chloride brings about inferior results since Indirect Oxidation with Organic Mediators
the current drops to zero before the cross-
coupling reaction is completed. Besides metal and nonmetal redox sys-
Iodine-assisted cleavage of the vicinal tems, organic redox systems are also
diol group of dextran has been inves- important electron carriers for indirect
tigated [77]. Dialdehyde starch (63) can electrooxidation.
RO R1 MeCN-Nal/Et4NClO4-(Pt) RO R1
P(O)H− + HN P(O) N
RO 70∼91% yields RO
R2 R2
(59) (60) (61)
Scheme 22 Cross coupling of dialkylphosphites with amines to dialkylphosphor-amidates.
CH2OH CH2OH
O O
2n IO4−
OH O
>90% yield O
n CH CH n
OH
(62) (63)
O O
Scheme 23 Dialdehyde starch by oxidative cleavage.

R3
IO3− ORuSiW11O395− (64)

R1 R2
CHO
IO4− (H2O)ORuSiW11O395−
Anode R1 (65)
R2
Scheme 24 Mediated cleavage of aryl olefin to aryl aldehyde.
R2 PhCN/2,6-lutidine-Et 4 OTs-(C/Pt) R1
CHOH C O
R1 +• − R2
Ph S Me Ph S Me
(66) − − (67)
−e−
68∼69% yields
1.5 V vs. SCE
Anode 10∼15 F mol −1
Scheme 25 Oxidation of secondary alcohols with thioanisole as organic redox catalysts.
15.2.2.1 Mediators Containing Sulfur and are also considered to be key intermedi-
Selenium Elements ates [83]. Synthesis of chromans by pho-
The oxidation of secondary alcohols (66) tosensitized electrooxidation of sulfides
to (67) is possible by indirect electrooxi- mediated by methylene blue has also been
dation utilizing thioanisole as an organic achieved [84]. Electrosynthesis of α-keto
redox catalyst in a PhCN-2,6-lutidine- acetals by a selenium-catalyzed transfor-
Et4 NOTs-(C/Pt) system at 1.5 V vs. SCE mation of aryl methyl ketones has been
(Scheme 25) [81] and is also performed in accomplished [85].
the presence of 2,2,2-trifluoroethanol [82].
It is suggested that the initially formed 15.2.2.2 Mediators Containing Nitrogen
cation radical sulfide species derived from An effective and mild electrocatalytic pro-
the direct discharge of the sulfide procedure for the deprotection of the 1,3-
vides phenylmethyl-alkoxysulfonium ions, dithiane group of (68), giving the ke-
which are transformed to (67) and tone (67), has been developed by using
thioanisole. a small amount of tris(p-tolyl)amine as
A novel electron carrier-mediator system a homogeneous electron-transfer catalyst
has been devised by employing a PhCN- (Scheme 26) [86]. The scope and limita-
2,6-lutidine-Et4 NBr-(C/Pt) system in the tions are discussed in detail [87]. The
presence of n-octyl methyl sulfide as a method can be applied also for oxidative
mediator. The reaction is probably initi- removal of the 4-methoxybenzyl thioether
ated by the discharge of the bromide ion, protecting group from poly-cystinyl pep-
which provides bromo cation or bromine. tides [88].
Alkoxysulfonium ions produced by the re- The brominated triaryl amines have
action of the sulfide with bromo cation been shown to be good mediators for
R1 R2 R1 R2
+
C •
C
S S S S
+•
Ar3N Ar3N
(68) (69)
−e−
Ar = p-MeC6H4
Anode H2O
R1
R1 HO R2
Quantitative
C O • C
R2 (67) S S
+ +• (70)
Ar3N Ar3N
S S
−e−
(71) Anode
Scheme 26 Electrocatalytic deprotection of 1,3-dithianes.
the indirect electrooxidation of organic carried out in an MeCN/CH2 Cl2 (5 : 1)-

compounds [89]. The stable cation radi- LiClO4 -(Pt) system in a divided cell at
cal of tris(p-bromophenyl)amine can be an anode potential of +1.2 V versus
used as a homogeneous electron-transfer Ag/AgCl to generate (73) in 83∼95% yields
catalyst for the mild oxidative removal (Scheme 27) [93–96]. The reversible po-
of the p-methoxybenzyl ether-protecting tential of the redox couple (Br-C6 H4 )3 N+• /
group [90–92]. The electrolysis of (72) is (Br-C6 H4 )3 N (E ◦ = +1.05 V vs. SCE) is
OMe OMe
MeCN/CH2Cl2-LiClO4-(Pt)
+•
OR (Br-C6H4)3N (Br-C6H4)3N CHO
−
(72) (73)
−e−
83∼95% yields
Anode
1.2 V vs. Ag/AgCl
Scheme 27 Oxidative cleavage of the benzyl ether–protecting group.
MeO OMe O
Me Me Me
OC6H5 MeO OMe O

(74) (75) (76)
MeOH/CH2Cl2-Bu4NBF4-(C) Conversion yield 90%
Scheme 28 Oxidation of m-phenoxytoluene to 2-methylbenzoquinone.

about 550 mV more negative than the acetals as major products [101]. The in-
irreversible oxidation potentials of (72). direct electrooxidation of ethers with ni-
The method usually gives 75∼95% yields trate radicals proceeds smoothly in an
of R-OH. Tris(p-bromophenyl)amine and aq. MeCN-LiNO3 -(Pt) system to afford
can also be used as an organic mediator the corresponding acids and/or ketones
for the oxidation of m-phenoxytoluene in good yields [102]. Recently, addition
(74), giving 2-methylbenzoquinone (76) of nitrate radicals to a C≡C triple bond
(Scheme 28) [97] and also for benzyl al- in the alkynyl ethers, as cis(or trans)-
cohols in high yield [98]. It is found that alkoxy-2-(hex-1-ynyl)-cyclopentanes (or cy-
the amine also proves to be an effec- clohexanes) yields anellated tetrahydrofu-
tive mediator for the indirect oxidation of ran derivatives with high diastereoselec-
amines. Benzyl amines can be converted to tivity, including oxidative, self-terminating
the corresponding Schiff base in excellent radical cyclizations [103]. Hydroxylamines
yield [99]. can be converted into the corresponding
Nitrogen compound-mediated electroox- nitrones by electrooxidation with bromo
idations of alcohols to aldehydes and cation mediators [104].
ketones have recently been developed. Nitroxyl radicals can be oxidized
The nitrate radical-mediated oxidation to N -oxo ammonium salts that are
of secondary alcohols (77)→(78) occurs themselves useful oxidants for primary
in an MeCN-H2 O(9 : 1)-LiNO3 -(Pt) sys- and secondary alcohols. Recently, the
tem (Scheme 29) [100]. Primary alcohols behavior of different nitroxides as catalysts
are also electrooxidized indirectly by us- for alcohol oxidation has been studied
ing electrogenerated nitrate radicals as by quantum chemical calculations [105].
a mediator in an MeOH-LiNO3 /H2 SO4 - Generally, 2,2,6,6-tetramethylpiperidine
(Pt) system to give the corresponding N -oxyl (TEMPO) (80) is used for the
MeCN/H2O(9/1)-LiNO3 -(Pt)
OH NO3• NO3− O
(77) −e− (78) 80% yield
Anode
Scheme 29 Nitrate-mediated oxidation of alcohols.
+ RCH2OH
N
(82)
−e−
(81) −H+
O
+
N
RCHO
O
Anode (83)
N N
(80) (79)
O OH
•
Scheme 30 Nitroxyl-radical-mediated selective oxidation of primary alcohols.

indirect electrooxidation of alcohols (82) (84) (Scheme 31) [109]. 4-Chlorobutanal,

(Scheme 30) [106]. The nitroxyl-mediated cyclopropylaldehyde, and m-phenoxyl-
oxidation of alcohols to aldehydes (83) and benzaldehyde are also prepared in the two-
ketones is achieved in an MeCN-LiClO4 - phase system [110]. Indirect electrooxida-
2,6-lutidine-(Pt) system in the presence of tion of 6β-methyl-3β, 5α-dihydroxy-16α,
(80) in a divided cell. Primary alcohols 17α-cyclohexanopregnan-20-one are indi-
are selectively oxidized at −60 ◦ C and rectly electrooxidized to the corresponding
secondary alcohols react more slowly than 5α-hydroxy-3,20-dione using sodium bro-
primary ones. mide and substituted TEMPO as the
A double mediatory system consist- mediating couple [111].
ing of N -oxoammonium salts and active A graphite felt electrode bearing the
bromine species, generated from 2,2,6,6- cross-linked 4-amino-TEMPO for alcohol
tetramethylpiperidine-1-oxyl derivatives oxidation has been prepared and the
and bromide ions as recyclable reagents modified electrode can be used for the con-
is shown to be useful for the selective version of nerol to neral selectively with a
electrooxidation of primary and secondary turnover number higher than 1560 [112].
alcohols to aldehydes and ketones, in an 4-Amino-TEMPO, immobilized through
aqueous-organic two-phase system [107]. an amide linkage to poly(acrylic acid),
The double mediatory system is supe- can be used for the electrocatalytic oxi-
rior to both direct oxidation and com- dation of thiols [113]. Methyl-substituted
binations [108]. Such a double-mediatory diols on a TEMPO-modified graphite felt
system is found to be effective for the electrode in the presence of (–)-sparteine
preparation of vicinal tricarbonyl com- undergo enantioselective, electrocatalytic
pounds (85) from 2,3-dihydroxyalkanoates lactonization in good enantiomeric excess
OH O Br−, 80 O O
aq. CH 2Cl2 AcONa (Pt)
R1 OR2 R1 OR2
50∼90% yields
OH O
(84) (85)
Scheme 31 Oxidation of 2,3-dihydroxyesters to vicinal tricarbonyl compounds with bromide and 80.
• R
N O CH OH
−e− R′
(89) (86)
O
−H+
O
R
N OH C O
R′
Anode O (88) (87)
Scheme 32 Oxidation of alcohols with N-hydroxyphthalimides as mediator.

more than 95% in acetonitrile [114, 115]. decane-N -oxyl, has been reported [117]. A
However, the kinetic resolution of 2- preparative electrocatalytic oxidation of
phenylethanol by indirect oxidation with racemic 1-phenylethanol on the chiral
TEMPO in the presence of sparteine has N -oxyl catalyst yields 50∼70% of enantio-
been questioned [115]. purity (S values: 4.1∼4.6). Several ex-
(d,l)-cis,cis-4-Benzoyloxy-2,2,8α-trimeth- amples of N -oxyl derivatives are listed
yldecahydroquinolinyl-N -oxyl is found to in Table 2.
be a good mediator for selective elec- N -Hydroxyphthalimide (88) has also
trooxidation of primary and secondary been shown to be an effective mediator
alcohols [116]. The first example of the for the oxidation of alcohols [120]. The
electrochemical method for the efficient, oxidation process depicted in Scheme 32
enantioselective oxidation of racemic sec- is suitable for the oxidation of secondary
alcohols using a chiral nitroxyl radical, for alcohols (86). N -Hydroxyphthalimide also
example, (6S,7R,10R)-4-acetylamino-2,2,7- plays an important role as a mediator for
trimethyl-10-isopropyl-1-azaspiro[5.5]un- deprotection of the 4-phenyl-1,3-dioxolane
Tab. 2 N-Oxyl derivatives used for electrooxidation of alcohols as mediators
Mediator system R Electrolysis conditions Product yield References

N-Oxyl [%]
H aq.CH2 Cl2 -NaBr/NaHCO3 -(Pt) 90 108

•
aq.CH2 Cl2 -Bu4 NPF6 -(Pt) – 105
R N O
CN aq.CH2 Cl2 -NaBr/NaHCO3 -(Pt) 91 108
OMe aq.CH2 Cl2 -NaBr/NaHCO3 -(Pt) 93 105, 108
(4-R-TEMPO) PhCO2 aq.CH2 Cl2 -NaBr/NaHCO3 -(Pt) 90∼98 108
aq.CH2 Cl2 -NaBr/NaHCO3 -(Pt) 70 110
61∼93 107, 109
NHAc aq.CH2 Cl2 -NaBr/NaHCO3 -(Pt) – 111
p-Bu-C6 H4 CO2 aq.CH2 Cl2 -NaBr/AcONa-(Pt) 93 108
Polymer-CONH MeCN-NaClO4 /2,6-Lutidine-(C) 90∗ 112–115
C = graphite felt
A PhCO2 CH2 MeCN/H2 O(7/1)-Et4 NBF4 -(Pt) 33∗ 118
75 119
B PhCO2 MeCN-NaClO4 /2,6-Luitidine-(C) 82.7∼96.7 116
C = glassy carbon
C NHAc MeCN-NaClO4 /2,6-Lutidine-(C) 51.4∼63.9 117
C = graphite felt
D MeCN-NaClO4 -(C) 54∼81 120–122
E, F aq.CH2 Cl2 -Bu4 NPF6 -(Pt) – 105
R R R O
N O• H O N O•
N O• N O•
A N N O E
D F
B C
O O
•
•
∗ Current efficiency.
OMe OMe
H2O-K2S2O8 -(CO2K)2
Me CHO
S2O82− 2SO42−
(90) (91) 45∼82% yields
−2e−
Anode
Scheme 33 Oxidation of p-methoxytoluene to anisaldehyde with peroxidisulfate as mediator.
protecting group as well as the vicinal in 45∼82% yield (Scheme 33) [123]. Silver
position to amides and lactams in 54∼81% salts, cupric sulfate, copper(II) oxide,
yields [121, 122]. and copper metal can be used in place
of (CO2 K)2 . The quinone/hydroquinone
15.2.3 redox systems also play an important
Indirect Oxidation with Other Redox role for the electrooxidative conversion
Systems of alcohols to aldehydes. Conversions
have been achieved in a solvent-free sys-
Redox systems other than halide salts are tem [124]. A glassy carbon electrode with
also used for catalytic indirect electrooxida- modified quinone/hydroquinone has also
tion. For instance, p-methoxytoluene (90) been used for the oxidation [125]. Flavin
can be oxidized in an aqueous K2 S2 O8 - analogs proved to be useful for the photoin-
(CO2 K)2 system to give anisaldehyde (91) duced oxidation of benzyl alcohols [126].
Tab. 3 Metal in redox systems and their oxidation-reduction potentials (E◦ )
Redox system E◦ (N.H.E.) value in

acidic media
Co3+ + e− −−−→ Co2+ 2.00

Ce4+ + e− −−−→ Ce3+ 1.81
MnO4 − + 8H+ + 5e− −−−→ Mn2+ + 4H2 O 1.51
Mn3+ + e− −−−→ Mn2+ 1.51
PbO2 + 4H+ + 2e− −−−→ Pb2+ + 2H2 O 1.46
Cr2 O7 2− + 14H+ + 6e− −−−→ 2Cr3+ + 7H2 O 1.33
Tl3+ + 2e− −−−→ Tl+ 1.25
MnO2 + 4H+ + 2e− −−−→ Mn2+ + 2H2 O 1.23
Fe3+ + e− −−−→ Fe2+ 0.77
Fe(CN)6 3− + e− −−−→ Fe(CN)6 4− 0.69
Sn4+ + 2e− −−−→ Sn2+ 0.15
TiO2+ + 2H+ + e− −−−→ Ti3+ + H2 O 0.10
Ti3+ + e− −−−→ Ti2+ −0.37
Cr3+ + e− −−−→ Cr2+ −0.41
15.2.4 (5) that can be used without further

Metal Ion-assisted Indirect Oxidation purification before and after electrolysis;
and (6) that can preferably be used in the
15.2.4.1 Indirect Oxidation with Metal Ion
in-cell method.
Redox Systems
Metal ions that are suitable as oxidizing
15.2.4.2 Indirect Oxidation with Nickel
or reducing agents are listed in Table 3 (Ni) and Cobalt (Co) Compounds
together with their oxidation potentials [1].
Primary alcohols are readily oxidized to
After oxidizing organic substrates, the
acids by Ni(III) hydroxide as the electron
resulting metal ions in a low-valent state
carrier. An example is the electrooxida-
may be reoxidized by electrolysis and
tion of isoamyl alcohol (92) in H2 O-
this way converted to oxidants in a high
NaOH/Ni(OH)3 -(Pt) to give isovaleric acid
oxidation state, thus forming the redox
loop shown in Fig. 1. (93) in a good yield (Scheme 34) [127].
Success in indirect electrooxidation with A Ni metal complex is also effective
a metal redox carrier depends on the for methanol oxidation [128]. The in-
choice of a metal ion (1) that is best termediary aldehydes (95) are isolable
suited for the desired functionalization; by employing a two-phase system in
(2) that is soluble in the electrolysis media 30∼86% yields (Scheme 35) [129]. Under
in both the high and the low oxidation basic conditions, secondary alcohols are
states; (3) that is expected to undergo readily oxidized into the corresponding ke-
electrooxidative regeneration with high tones [130].
current efficiency as well as to react with Co(III)(OAc)3 can be used as a me-
the substrate in a high yield; (4) that can diator in an AcOH-AcONa/Bu4 NBF4 -(C)
be readily separated from the products; system at high current density [131].
Me Me
CHCH2CH2OH H2O-NaOH/Ni(OH)3-(Pt) CHCH2CO2H
Me 72.7% yield Me
(92) (93)
Scheme 34 Oxidation of primary alcohols to carboxylic acids with nickel(III) as mediator.
H2O-K2CO3/Ni(OH)3-(Ni/stainless)
R CH2OH R CHO
30∼86% yields
(94) Two-phase system (95)
Scheme 35 Oxidation of primary alcohols to aldehydes with nickel(III) as mediator.
OAc
(96) Co(OAc)3 Co(OAc)2 (97)
−e−
Anode
Scheme 36 Allylic acetoxylation of cyclohexene with cobalt(III)triacetate.

Allylic acetoxylation of cyclohexene (96) at ambient temperatures [133]. The mi-

at 80 ◦ C affords 3-acetoxycyclohexene (97) gration of the phenyl group in 1-bromo-
in 67% yield (Scheme 36). It was found 2,2-bis(ethoxycarbonyl)-2-phenylethane is
that the catalytic double-bond isomer- catalyzed by the action of cobalt in vitamin
ization of 3-phenylpropene proceeds by B12 derivatives [134].
the action of an electrochemically gener-
ated 17-electron Co(II) species [132]. The 15.2.4.3 Iron (Fe) Complex-assisted
cobalt(III)-mediated electrooxidative de- Oxidation
composition of chlorinated organics, that Fenton’s reagent [H2 O2 + Fe(II)] can
is, 1,3-dichloro-2-propanol, 2-monochloro- be used as a redox carrier for
propanol, and so on, has been performed the indirect hydroxylation of aromatic
OH
H2O2
Fe2+ (99)
(98)
H2O2 + Fe2+ Fe3+ + OH − + OH•

(a)
OH • + ArH [ArHOH] •
(b)
[ArHOH] • + Fe3+ Fe2+ + H+ + ArOH

(c)
e
Fe3+ Fe2+ (E0 = +0.7 V)
(d)
Scheme 37 Hydroxylation of aromatic compounds mediated by Fenton’s reagent.
R O R
H2O-H2SO4 -FeSO4-(Pt)
R = H (61%), R = Me (83%)
(100) (101)
Scheme 38 Side-chain oxidation of aromatic compounds mediated by Fe(II).
CO2H CO2H
O (103)
(102)
[Fe(IV)(O)(tsmp)]4− [Fe(III)(OH)(tsmp)]3−
−e−
pH = 8.0, +0.720 V vs. Ag/AgCl
Anode
Scheme 39 Allylic oxidation of olefins with an oxoferryl porphyrin complex.

compounds (Scheme 37) [135, 136]. The yields, respectively (Scheme 38) [137].
electrochemically generated hydroxy Selective allylic oxidation of olefins (102)
radical [OH]• affords an intermediate has been attained to give (103) in aqueous
[ArH-OH]• , which, on subsequent buffer solutions at pH 8 with an oxoferryl
oxidation with Fe3 + , gives phenol in porphyrin complex (Scheme 39) [138].
the manner shown in Scheme 37a→d. Alcohols have been converted into
Phenols (99) are obtained from benzene aldehydes mediated by a lipophilic β-
(98) and fluorobenzene by the above cyclodextrin bearing a ferrocene moi-
procedure in 64∼80% yield. This method ety [139]. Efficient indirect in situ electro-
can also be used for the oxidation regeneration of NAD+ and NADP+
of side chains of alkylbenzenes. For for enzymatic oxidations of butanol
example, methyl- and ethylbenzenes (100) and 2-hexen-1-ol leading to the corre-
afford benzaldehyde (101) (R = H) and sponding aldehydes using Fe bipyridine
acetophenone (101) (R = Me) in 61∼83% and phenanthroline complexes as redox
Tab. 4 Conditions and results in indirect electrooxidation with Cr(VI)
Substrate Mediator Product Electrolysis conditions References
R−CH–CH2 OH R−CH–CO2 H
| K2 Cr2 O7 | Cr2 O3 + H2 SO4 143
NHOAc NHOAc
p–Nitrotoluene H2 Cr2 O7 p-Nitrobenzoic Acid Cr2 (SO4 )3 + H2 SO4 148
m-Xylene Na2 Cr2 O7 m-Isophthalic Acid Cr2 O3 + 50% H2 SO4 (Pb)(H3 PO4 ) 144,145
p-Xylene Na2 Cr2 O7 Terephthalic Acid Cr2 O3 + 50% H2 SO4 (Pb)(H3 PO4 ) 144,145
Na2 Cr2 O7 Terephthalic Acid Cr2 O3 + 50% H2 SO4 (Pb)(H3 PO4 ) 144,145
CHO
Na2 Cr2 O7 Terephthalic Acid Cr2 O3 + 50% H2 SO4 (Pb)(H3 PO4 ) 144,145
CO2H
p-Cymene Na2 Cr2 O7 Terephthalic Acid Cr2 O3 + 50% H2 SO4 (Pb)(H3 PO4 ) 144,145
CH3 O
Na2 Cr2 O7 Cr2 O3 + conc. H2 SO4 (PbO2 –Pb) 146
SO2NH2 NH
SO2
Anthracene Na2 Cr2 O7 Anthraquinone Cr2 (SO4 )3 + H2 SO4 147
O
CH3
Cr(VI)
NH
85% yield
SO2NH2 SO2
(104) (105)
Scheme 40 Industrial saccharin synthesis with chromic acid as mediator.

catalysts have been performed [140]. Sul- can usually be readily oxidized to car-
fonated ferrocenes have been applied boxylic acids with Cr(VI) and selected re-
as redox mediators in enzyme elec- sults are shown in Table 4 [143–145]. The
trodes [141, 142]. recovered chromium oxide is subjected
to electrolysis in a strong mineral acid,
15.2.4.4 Indirect Oxidation with Chromic that is, H2 SO4 , H3 PO4 , by using a PbO2 -
Acid [Cr(VI)] Pb electrode system to generate Cr(VI)
Chromic acid is a potential electron carrier species. The chromic acid process is used
for indirect electrooxidation. For example, in a successful industrial indirect pro-
p-xylene may be converted to terephthalic cess for saccharin synthesis (104→105),
acid on treatment with Cr(VI). Simi- (Scheme 40) [146]. The reaction has been
larly, methyl groups on aromatic rings applied to the commercial-scale synthesis
NO2 NO2 NH2
1)*
2)*
CH3 CO2H CO2Et

H2Cr2O7 Cr2(SO4)3
92% yield
(106) (107) (108)
1)* Electroreduction
Anode 2)* Esterification
Scheme 41 p-Aminobenzoate synthesis applying mediated side-chain oxidation.
CO2H CO2H
H2O-Na2ClO4 /Cr(V)-(Pt)
53% yield
O
(109) (110)
Cr(V) = oxo(5,10,15,20-tetrakis(2,6-dimethyl-3-
sulfonatophenyl)porphinato)chromium(V)
Scheme 42 Epoxidation of alkenes with an Cr(V)-complex as mediator.
Br NH2 Pd(II) R
3 (111)
−
−e
+• R
Br NH2 Pd(0) O
3
(112)
Anode 40∼90% yields
Scheme 43 Electrochemical Wacker oxidation.

of anthraquinone from anthracene in Ger- porphinato]chromium(V) in aqueous so-

many and the UK [147]. Synthesis of lution. 3-Cyclohexene-1-carboxylic acid
ethyl p-aminobenzoate benzocaine (108) (109) can be converted into the cor-
from p-nitrotoluene (106) has been ac- responding epoxide (110) in 53% yield
complished by using a two-stage electro- (Scheme 42) [150].
chemical process: (1) Cr2 (SO4 )3 is elec-
trochemically oxidized to H2 Cr2 O7 , which 15.2.4.5 Palladium (Pd)-assisted Oxidation
can react with (106) outside the cell to The electrochemical Wacker-type oxida-
give the acid (107); (2) electroreduction tion of terminal olefins (111) by using
of (107) with a rotating tin-plated copper palladium chloride or palladium ac-
cathode gives p-aminobenzoic acid, ester- etate in the presence of a suitable ox-
ification of which provides (108) in 92% idant leading to 2-alkanones (112) has
yield (Scheme 41) [148]. been intensively studied. As recyclable
A method for preparing a Ti/Cr2 O3 double-mediatory systems (Scheme 43),
electrode has been developed for the quinone, ferric chloride, copper acetate,
indirect electrooxidation of 2-propanol and triphenylamine have been used
to acetone [149]. Epoxidation of alkenes as co-oxidizing agents for regenera-
has been performed using oxo[5,10,15,20- tion of the Pd(II) catalyst [151]. The
tetrakis(2,6-dimethyl-3-sulfonatophenyl) palladium-catalyzed anodic oxidation of
Tab. 5a Pd(II)-mediated Wacker oxidation of olefins
Substrate Conditions Mediator Product Yield Reference

system [%]
1-Heptene A A 2-Heptanone 64∗ 118

1-Octene A A 2-Octanone 83∗ 118
trans-2-Octene B B 2-Octanone 76 153
1-Decene B C 2-Decanone 68 153
A A 91∗ 118
C C 63 119
Vinylcyclohexane A A Acetylcyclohexane 33∗ 118
Cyclopentene C C Cyclopentanone 75 119
Cyclohexene B B Cyclohexanone 77 153
A A 29∗ 118
C C 83 119
Cycloheptene A A Cycloheptenone 72∗ 118
Styrene B B Acetophenone 61 153
A A 35∗ 118
C C 56 119
Note: Electrolysis conditions: A MeCN/AcOH(7/1)-NaClO4 /NaOAc-(Pt);

B MeCN/H2 O(7/1)-HClO4 /Bu4 NClO4 -(Pt);
C MeCN/H2 O(7/1)-Et4 NBF4 -(Pt)
Mediator systems: A Pd(OAc)2 /Cu(OAc)2 ; B [(L2 )2 MnO2 Mn(L2 )2 ](ClO4 )4 ;
C Pd(OAc)2 /Benzoquinone
Tab. 5b Pd(II)-mediated Wacker oxidation of olefins 514
Olefin Conditions Products Yield Reference

[%]
Divided Undivided
cell cell
H2C CH (CH2)7 CH CH CH2 OAc B Ac (CH2)7 CH CH CH2 OAc 75 – 119

15 Indirect Electrochemical Reactions
H2C CH (CH2)2 CH(CO2Me)2 B Ac (CH2)2 CH(CO2Me)2 69 – 119
H2C CH CH (CH2)6 Me A H2C CH C (CH2)6 Me 70 41 151
HO O
A 64 66 151
H2C CH CH2 O2C Ac O2C
H2C CH (CH2)7 CHO A Ac (CH2)7 CHO 46 74 151
O A O 89 60 151
CO2Me
CO2Me
Ac
B 76 – 119
CO2Me A CO2Me 93 90 151

Ac
O O
B 82 – 119
O A O 79 48 151
Ac
CO2Me CO2Me
A 74 72 151
Ac Ac
N N
CO2Et CO2Et
A 57 85 151
O Ac
O
O O
OMe A OMe 82 89 151

Ac
Ph Ph
Note: Conditions: A MeCN/H2 O(7/1)-Et4 NOTs-(Pt/Pt);

B MeCN/H2 O(7/1)-HClO4 /Bu4 NClO4 -(Pt).
15.2 Indirect Electrooxidation
515
1-alkenes (111) in the presence of ben- The methoxycarbonylation of olefins

zoquinone derivatives as cooxidants also proceeds smoothly by using an electro-
affords the corresponding 2-alkanones generated Pd(II) to give a mixture of
(112) in good yields, depending on the branched and linear esters (114 and 115) in
type of quinone. The Wacker-type re- good yields (Scheme 44) [154]. The Pd(II)-
action of the compound in the pres- assisted anodic carbonylation is carried
ence of either benzoquinone or 2- out in an MeOH-PdCl2 /LiCl-(C) system
methylbenzoquinone gives the ketone in by bubbling carbon monoxide in to the
over 90% yields [119, 152]. The Wacker ox- solution. The results are shown in Table 6.
idation of cyclohexene as a cyclic olefin The oxidation of olefins (116) with the
also proceeds with good yield in an electrogenerated Pd(II) by using Pd-Pt
MeCN/H2 O (7/1)-Bu4 NClO4 /Pd(OAc)2 - electrodes has been shown to proceed
(Pt) system [153]. Some products ob- through the formation of a Pd(II)-olefin
tained by the Wacker-type reaction are complex, giving the carbonyl compound
shown in Table 5. (115), (Scheme 45) [155].
Pd(II) HCR CH2 + CO + MeOH

(113)
−e−
Pd(0) RCH(CO2Me)Me + RCH2CH2CO2Me
Anode (114) 43∼80% yields (115)
Scheme 44 Palladium(II)-catalyzed methoxycarbonylation of olefins.
Tab. 6 Pd(II)-mediated carbonylation of olefins [154]
Olefin Product Yield [%]

2
R
R1 CH C H
H R1 −CH2 CH2 CO2 Me R1 C CO 2Me
R1 R2 Me
Me(CH2 )3 H 17 56
Me(CH2 )4 H 23 69
Me(CH2 )5 H 24 72
Me(CH2 )9 H 23 71
Me(CH2 )3 Me 12 38
Me Me 11 32
CH
Me
(CH2 )4 12 38
Ph H 23 71
Note: The electrochemical carbonylation is carried out in an

MeOH-PdCl2 /LiCl-(C) system and bubbling carbon monooxide into
the solution.
H2SO4-(Pd/Pt), 80°C
H2C CH2 H3C CHO
90% current efficiency
(116) (117)
Scheme 45 Conversion of ethene to acetaldehyde at a Pd/Pt-anode.
Pd-hydroquinone-mediated electroche- an indirect electrochemical carbonylation

mical 1,4-diacetoxylation of cyclohexa-1,3- of aromatic amines with a palladium
diene (118), leading to 1,4-diacetoxycyclo- catalyst. The electrolysis of the amines is
hex-2-ene (119), has been investigated carried out in an MeOH-AcONa-(C) by
(Scheme 46) [156]. Palladium-catalyzed in- bubbling in CO gas in the presence of
direct electrochemical monoacetoxylation Pd(OAc)2 and Cu(OAc)2 and the results are
of olefins has been attained in an illustrated in Table 7 [157]. Propylene can
MeCN/AcOH-NaClO4 /AcONa/Pd(OAc)2 - be converted mainly to acetic and formic
Cu(OAc)2 -(C) system. The acetoxylation acids via acetone in an Hg(II)-HClO4 -(Pt)
of cyclohexene produces unsaturated es- system [158].
ters with less current efficiency, giving
a 1 : 1 mixture of allylic and vinylic 15.2.4.6 Ruthenium (Ru)-assisted
products [118]. Oxidation
Aromatic carbamates, precursors of iso- Instead of strong oxidants such as oxo com-
cyanates, have been electrosynthesized by plexes of transition metals (MnO4 − and
AcOH-LiOAc/Pd(OAc) 2 -(Pt)
AcO OAc
Hydroquinone
74% yield
(118) (119)
Scheme 46 Pd-mediated diacetoxylation of cyclohexene.
Tab. 7 Pd(II)-catalyzed N-carbonylation of aromatic amines [157]
Substrate Products Yield

[%]
C6 H5 NH2 C6 H5 NHCO2 Me 99
p-MeC6 H4 NH2 p-MeC6 H4 NHCO2 Me 85
o-MeC6 H4 NH2 o-MeC6 H4 NHCO2 Me 84
p-ClC6 H4 NH2 p-ClC6 H4 NHCO2 Me 96
p-HOC6 H4 NH2 p-HOC6 H4 NHCO2 Me 78
2,6-Me2 C6 H3 NH2 2,6-Me2 C6 H3 NHCO2 Me 95
p-MeC6 H4 NH2 p-MeC6 H4 NHCO2 Me 98
Note: Electrolysis Conditions: MeOH-AcONa/CO-(Graphite)

Mediator System: Pd(OAc)2 /Cu(OAc)2 .
CrO3 ), a mild electrooxidation technique Another versatile mediatory system for var-
using Ru complexes is available for the ious oxidative transformations (126→127)
oxidation of alcohols, aldehydes, cyclic is a Ru(IV)/Ru(VIII) redox system. Ruthe-
ketones, and C−H bonds adjacent to nium tetroxide, RuO4 , generated in situ
olefinic and aromatic groups [159]. The in aqueous sodium chloride can act as
kinetics of electrooxidation of alcohols an efficient oxidant in an organic solvent
by [(bpy)2 pyRu(IV)(O)]2+ has been infor the oxidation of alcohols, aldehydes,
vestigated [160]. Bispyridyl, pyridyl com- amines, and so on (Scheme 50) [165–167].
plexes of ruthenium(IV), for exam- The cleavage of cyclododecene leading to
ple, (bpy)2 pyRu(OH2 )2+ /(bpy)2 pyRuO2+ the corresponding dicarboxylic acid has
and/ or (trpy)(bpy)Ru(OH2 )2+ /(trpy)(bpy) been done by employing ruthenium tetrox-
RuO2+ systems, proved to be good cat- ide and cerium salt as double-mediatory
alysts for alcohols, aldehydes, ethers, systems [168]. The electrooxidation of the
and for olefin oxidation (120→121) alcohol (128) proceeds in a CCl4 -sat. aque-
(Scheme 47) [161–164]. Cyclohexene ous NaCl-(Pt) system in the presence of
(122→123) (Scheme 48) and p-xylene a catalytic amount of RuO2 •2H2 O, pro-
(124→125) (Scheme 49) are dissolved or viding (129) in 93% yield (Scheme 51);
dispersed in an aqueous buffer solution of the scope of the reaction as well as
the catalyst, and electrolyzed at potentials the procedures are reported [169]. Ben-
that are sufficient to cause the oxidation zyl alcohols can be oxidized into their
of Ru(II)→Ru(IV) (0.6∼0.8 V vs. SCE). corresponding benzaldehydes and benzoic
(typy)(bpy)Ru(II)(H 2O)(ClO4)2/
R (typy)(bpy)Ru(IV)O(ClO 4)2 R
CH OH O
R′ Phosphate buffer-LiClO 4-(Pt) R′
(120) trpy = 2,2′,2″-terpyridine (121)
bpy = 2,2′-bipyridine
Scheme 47 Ruthenium(IV)-complex-mediated oxidation of alcohols.
O
−4e−
(122) (123)
Scheme 48 Allylic oxidation of alkene with Ru(IV)-complexes.
CH3 CO2H
−8e−
CH3 CO2H
(124) (125)
Scheme 49 Side-chain oxidation of aromatic compounds with Ru(IV)-complexes.

[Cl] + RuO2 Product

(126)
−2e−
Cl − RuO4 Substrate
(127)
Anode
Scheme 50 Ruthenium tetroxide-mediated oxidation.
−2e−
93% yield
OH O
(128) (129)
Scheme 51 Ruthenium tetroxide-mediated oxidation of alcohols.
−4e−
N 92% yield N O
CO2Et CO2Et
(130) (131)
Scheme 52 Rutheniumtetroxide-mediated oxidation of amines to amides.
acids [170]. Similarly, the amine (130) can alcohols (132) to ketones (133) under
be oxidized smoothly to the amide (131) in basic conditions has been developed
good yield (Scheme 52) [166]. Various fac- (Scheme 53) [182]. The Ru(VII) species are
tors related to the yield and selectivity for regenerated in either the Bu4 NOH or
the indirect electrooxidation of diisopropy- the Bu4 NOH/Br4 NBr system under ba-
lideneglucose to ulose have been stud- sic conditions.
ied [171, 172]. The indirect electrosynthe-
sis of 1,3-dichloroacetone is also well estab-
lished by employing the Ru(VIII)/Ru(IV) 15.2.4.7 Osmium (Os)-assisted Oxidation
and [Cl+ ]/[Cl− ] double-mediatory sys- Osmium tetroxide is a well-known ox-
tem [173]. 2-Methylnaphthalene can be oxi- idizing agent for the conversion of
dized to vitamin K3 under mild electrolysis olefins (134) to 1,2-diols (135). The in-
conditions [174]. Some results are indi- direct electrooxidation of olefins by us-
cated in Table 8 [175–180]. The modified ing OsO4 -K3 Fe(CN)6 in alkaline media
carbon electrode bearing functionalized as a double mediator has been reported
polypyrrole-RuO2 films can be used for (Scheme 54) [183]. The process consists of
benzyl alcohol oxidation [181]. three reaction steps: (1) oxidation of olefins
A novel Ru(VII)/Ru(IV) redox sys- (134) by [OsO4 (OH)2 ]2− in alkaline solu-
tem for the indirect electrooxidation of tions; (2) regeneration of [OsO4 (OH)2 ]2−
R
[Br] + [Ru(IV)O3]2− O
R′
(133)
−2e−
R
Br − [Ru(VII)O4] − CH OH
Anode R′
(132)
Scheme 53 Ruthenium(VII)-mediated oxidation of alcohols.
K4Fe(CN)6
Os6+ R CH CH R′
(134)
−2e−
Os8+ R CH CH R′
K3Fe(CN)6
Anode OH OH
(135)
Scheme 54 Osmiumtetroxide-mediated dihydroxylation of alkenes.
by the oxidation of [OsO2 (OH)4 ]2− with of potassium osmate [K2 OsO2 (OH)4 ]
ferricyanide; and (3) electro-regeneration and a small amount of chiral ligands
of ferricyanide. The gaseous olefins (ethy- [(DHQD)2 PHAL] (Scheme 55). Chiral
lene, propylene, and so on) are bubbled induction is also found to occur in
through an aqueous KOH/K3 Fe(CN)6 / different systems such as I2 /K2 CO3 /
OsO4 solution to form glycols in 94∼99% K2 OsO2 (OH)2 and I2 /K3 PO4 /K2 HPO4 /
yield. A large excess of ferricyanide K2 OsO2 (OH)2 [185, 186].
is effective in oxidizing [OsO2 (OH)4 ]2− The cleavage of a double bond
to [OsO4 (OH)2 ]2− rapidly and quanti- can be performed by employing
tatively. During the overall process of a K2 OsO2 (OH)4 /HIO4 double-mediatory
olefin oxidation to the glycol, ferricyanide system (Scheme 56) [187]. The indirect
is converted to ferrocyanide that sepa- oxidative fission of the double bond
rates out because of its lower solubil- of olefin (139) by the double-mediatory
ity. The regeneration of ferricyanide is system proceeds in a stepwise manner
performed electrochemically by using an involving diol (140) formation and
oxygen-depolarized cathode. subsequent cleavage of the C–C bond,
Excitingly, the electrochemical Os-cata- leading to the ketone (141).
lyzed asymmetric dihydroxylation of ole-
fins with Sharpless’s ligands yielding
the chiral diol (138) via the chiral 15.2.4.8 Indirect Oxidation with
adduct (137) has been reported [184]. Manganese [Mn(III)]
The asymmetric dihydroxylation of Alkylbenzenes can be indirectly oxidized
olefins (136) is performed by recycling to the corresponding aromatic aldehy-
a catalytic amount of potassium des with Mn2 (SO4 )3 . Regeneration of
ferricyanide [K3 Fe(CN)6 ] in the presence Mn(III) is carried out by electrolysis in
Tab. 8a Indirect electrooxidation with ruthenium mediators
Substrate Product Yield [%] References
Isopropanol Acetone 90∗ 165–167

Pentanol Pentanal 41 177
Octanol Octanal 98 177
Cyclohexanol Cyclohexanone 77 177
Cyclododecanol Cyclododecanone 88 169
2-Nitro-3-nonanol 2-Nitro-3-nonanone 83 169
1,1-Dichloro-2-octanol 1,1-Dichloro-2-octanone 83 169
1-Octanol 1-Octanoic Acid 68 169
1-Menthol 1-Menthone 88 169
Cyclohexylmethanol Cyclohexanecarboxylic Acid 68 169
Allyl Alcohol Acrylic Acid 52 177
Benzyl Alcohol Benzoic Acid 51 177
Heptanal Heptanoic Acid 86 169
OH O 47 178
Et CH CH2 OH Et C CH2 OH
OH O 41 178
Me CH (CH2)2 OH Me C (CH2)2 OH
HO (CH2)2 OH γ –Butyrolactone 44 178
Decane-1,5-diol Decan-5-olide 79 169
Undecane-1,6-diol 6-Oxoundecanoic Acid 65 169
Undecane-1,10-diol 10-Oxoundecanoic Acid 89 169
OH O 85 177
Ph CH CH2 Cl Ph C CH2 Cl
OH O 83 177
Ph CH CH2 Br Ph C CH2 Br
OH O 98 177
Me CH CH2 Cl Me C CH2 Cl
OH O 97 177
Me CH CHCl Me Me C CHCl Me
OH O 98 173
Cl CH2 CH CH2 Cl Cl CH2 C CH2 Cl

OH O 89 178
OH
O
88 177
MeO CH2OH MeO CO2H
Methylphenylcarbinol Acetophenone 98 177
Note: Mediator System: RuO2 /H2 O/NaCl-NaH2 PO4 /Pt

Tab. 8b Indirect electrooxidation with ruthenium mediators
Substrate Mediator system Product Yield [%] References
Cyclohexene A 48 175
O
Cyclooctene B OHC-(CH2 )6 CHO 48 180
B OHC-(CH2 )4 CO2 Me 44 180
OMe
B 23 180
CHO
O
B 57 180
OAc O O
Ph−COMe A Ph−CO2 H 73 175
B CHO 31 180
OHC
A 49 175
O O CHO
O O
B 68 180
O O
O
O O
A 65 175
B 70 180
MeO MeO CHO
MeO MeO
Stilbene B Benzaldehyde 63∼72 180
4,4 -Dimethoxystilbene B Anisaldehyde 82 180
C O 71 176
OH
O
C 40 176
O O O
1 2 H2 O/Cl4 O 69∼87 179

R R
RuO2 /NaCl R
1
R
2
O
R1 = R2 = alkyl, Ph
Note: Mediator Systems: A H2 O/t-BuOH, [(trpy)(bpy)Ru(H2 O)]2+

B H2 O/C2 H4 Cl2 /NaIO3 , (Bu4 N)5 (H2 O)RuSiW11 O39
C H2 O/Phosphate Buffer, [(trpy)(bpy)Ru(H2 O)]2+ .
Ph
H
O H H OH
O
Ph Os O H
HOCH2 Ph
O
L*
(136) (137) (138)
Scheme 55 Electrochemical enantioselective Sharpless dihydroxylation of alkenes.
HO OH O
Step I Step II
(139) Os(VIII) Os(VI) (140) (141)

HlO4 HlO3
HlO3 HlO4
Scheme 56 Double-bond cleavage with osmiumtetroxide/periodate.
a 55% H2 SO4 -MnSO4 -(PbO2 /Pb) system, permanganate is also a useful electron car-
and Mn2 (SO4 )3 is regenerated in 68∼78% rier for the indirect side-chain oxidation of
current efficiency (or yield) [188–192]. The alkylbenzenes [198].
addition of ammonium sulfate to the elec- The electrooxidation of alcohols and
trolytic regeneration system can improve ethers into aldehydes is successfully
the current efficiency to 80∼97% [188, carried out by using the [(L2 )2 MnO2 Mn
189]. Benzaldehyde has been commercially (L2 )2 ]4+ / [(L2 )2 MnO2 Mn(L2 )2 ]3+ system
prepared from toluene by indirect elec- [199] and the results are indicated in
trooxidation with Mn2 (SO4 )3 by an in-cell Table 10 [200–204].
type method [1]. Carboxylic acids may be The electrogenerated Mn(III)-assisted
produced when the reaction of alkylben- coupling of various olefins with active
zenes with Mn2 (SO4 )3 is carried out at methylene compounds proceeds by indi-
higher temperatures or at low concentra- rect electrooxidation with a small amount
tion of sulfuric acid. The results obtained of Mn(OAc)2 in the presence or absence
by oxidation with Mn(III) are summarized of Cu(OAc)2 [196]. The Mn(III)-assisted
in Table 9. carboxymethylation of styrenes (142) af-
Potassium permanganate, KMnO4 , can fords γ -aryl-γ -lactones (143) in good cur-
also be regenerated under conditions in rent yields (Scheme 57) [194, 195, 206,
which the electrooxidation of a suspen- 207], (Table 9).
sion of tetravalent manganese oxide is Radical addition of polyhalomethanes
carried out on 10∼20 wt.% potassium to olefins can be initiated by electro-
hydroxide by using Ni-Fe electrodes at chemically generated Mn(III) species. The
80 ◦ C in the presence of KClO4 , KMnO4 , procedure offers an alternative method of
or K3 [Fe(CN)6 ]. The conversion yield of a radical addition reaction with an easy
MnO2 is up to 80∼97% [197]. Potassium control of the initiation via the current
Tab. 9 Indirect electrooxidation with manganese mediators
Olefin Nucleophile Product Yield [%] References
Cl3 CO2 H CO2H ∼84 193

OAc
(6/4)
CO2H
OAc
R CN H
C 76 194
CO2Et R
CO2Et
R
X
R
R = H, Me H2 C-(CO2 Et)2
78 195
R1 CN R2 ∼80∗ 195, 196

R2 CO2Et
Ar R1
O O
Ar
R1 R2 CN R1 R2 ∼60∗ 195, 196
CO2Et
NC CO2Et
R1 = Propyl, Pentyl, Hexyl; R2 = H
R1 = R2 = −(CH2 )n- n = 2, 3, 4, 5, 9 R1 R2 ∼55∗ 195, 196
NC CO2Et
R3 CN H 71∼79 195
R3 C
R2 CO2Et
R1 R2 CO2Et
R1
X
H2 C-(CO2 Et)2
R1 = R2 = R3 = H, Me F
Note: Electrolysis Conditions: AcOH/Ac2 O-AcONa-(C/C)

Mediator System: Mn(OAc)2 · 4H2 O/Cu(OAc)2 · H2 O
density. The several results are summa- are catalytically electrosynthesized on a

rized in Table 11 [208, 209]. large scale [193] (Table 9).
Carbohydrates such as 6-deoxyhexoses The effect of a surfactant such as do-
[210] and aldopentose [211] have been decylbenzene sulfonate (DBS) has been
oxidized electrochemically by using man- investigated and the DBS concentra-
ganese mediators. Manganese mediators tion slightly influences the current effi-
are also useful for the oxidation of α- ciency [213]. The oxidation of cinnamyl
amino acids [212]. Sorbic acid precursors alcohol to cinnamaldehyde with a solid
polymer electrolyte has been performed (146) is produced (Scheme 58) [216]. The
with high selectivity and current effi- electrolytic regeneration of CAN is per-
ciency [214]. formed in a 4 M HNO3 –(Pt/C) system
in 90∼98% current yield [218]. Ceric sul-
15.2.4.9 Indirect Oxidation with Cerium fate, Ce(IV)(SO4 )2 •4H2 O, is coordinated
(Ce) Complexes with a sulfate anion as well as water as
Cerium(IV) ion has been widely used ligands and this results in decreased oxi-
in the oxidation of secondary alcohols, dation power and solubility compared with
cleavage of cycloalkanones, oxidative hy- CAN. Ceric sulfate is used as an electron
drolysis of oximes, side-chain oxidation carrier in the ex-cell method and can be
of alkylbenzenes, quinone formation from regenerated in an H2 SO4 –(PbO2 /Pb) sys-
hydroquinones, sulfoxide formation from tem in 70% current yield [219], and also,
in a 5% H2 SO4 -(graphite) system in 70%
sulfides, and functionalization of nitrogen-
yield [220].
containing compounds [215]. The oxida-
The oxidation of toluene to benzalde-
tion power of Ce(IV) as an oxidant in-
hyde (max. yield 98.8%) can be performed
creases on the order of Ce(IV)/HClO4 >
in a Ce(ClO4 )3 –HClO4 –(Pt/Ti-Cu) sys-
Ce(IV)/HNO3 > Ce(IV)/H2 SO4 . For ex-
tem by using the in-cell method in an
ample, p-methoxytoluene can be ox-
undivided cell [28]. Indirect electrooxida-
idized with ceric ammonium nitrate, tions of organic compounds with Ce(IV)
[NH4 ]2 [Ce(NO3 )6 ], (abbreviated as CAN) are listed in Table 12 [221–230]. For the
in nitric acid even at room temper- electrogeneration of Ce(IV), platinized ti-
ature, but with Ce(SO4 )2 in sulfuric tanium or platinum oxide-on-titanium
acid elevated temperatures (80∼85 ◦ C) are electrodes are known to be suitable for con-
needed. A similar oxidation of toluene with tinuous oxidation of Ce(III) in perchloric
Ce(ClO4 )4 in perchloric acid readily affords acid.
benzaldehyde in 98.8% yield [28]. CAN is An alternative redox system, other than
composed of ammonium cations and hex- Ce(IV), for the oxidation of toluene to
anitratocerate anions (144) [216] (and is benzaldehyde has been developed by
very soluble in a variety of solvents [217]). utilizing the Co(III)-H2 SO4 system that
When Ce(IV) in the form of CAN is re- has an intrinsically higher redox potential.
duced to Ce(III), pentanitrocerate anion The advantage of the latter system is that
Ar R2
Ar R2 AcOH/Ac2O-AcONa-(C)
R1 C CH
R1 Mn(OAc)2, Cu(OAc)2
O
80% yield
(142) (143)
O
Scheme 57 Manganese(III)-assisted carboxymethylation of styrenes.
ROH ROH, −HNO3

[Ce(NO3)6]2− [Ce(NO3)6ROH]2− [Ce(NO3)5(RO)ROH] 2−
−ROH −ROH, HNO3
(144) (145) (146)
Scheme 58 Ligand exchange in cerium(IV)-complexes.

526
15 Indirect Electrochemical Reactions
Tab. 10 Indirect electrooxidation of alcohols, ethers and aromatics with manganese mediators
Substrate Conditions Mediator Product Yield References

system [%]
Ph−CH2 OH A A Ph−CHO 70 199

p-Me2 CH−C6 H4 −CH2 OH A A p-Me2 CH−C6 H4 −CHO 73 199
p-MeO−C6 H4 −CH2 OH A A p-MeO−C6 H4 −CHO 86 199
o-MeO−C6 H4 −CH2 OH A A o-MeO−C6 H4 −CHO 80 199
o, p-(Me)2 −C6 H3 −CH2 OH A A o, p-(Me)2 −C6 H3 −CHO 76 199
p-PhO−C6 H4 −CH2 OH A A p-PhO−C6 H4 −CHO 78 199
(Ph)2 CHOH A A (Ph)2 C=O 90 199
p-PhCH2 O−C6 H4 −CH2 OH A A p-PhCH2 O−C6 H4 −CHO 83 199
p-MeO−C6 H4 −CH2 OMe A A p-MeO−C6 H4 −CHO 79 199
p-MeO−C6 H4 −CH2 OC8 H17 A A p-MeO−C6 H4 −CHO 80 199
o-MeO−C6 H4 −CH2 OMe A A o-MeO−C6 H4 −CHO 94 199
Ph−CH=CH−CH2 −OH B C Ph−CH=CH−CHO 90 199
Benzene A B Benzoquinone 62∼70∗ 199
Toluene A 60 ◦ C B Benzaldehyde 80∗ 146, 190–192,
203, 204
m-Chlorotoluene A C m-Cl−C6 H4 −CHO 33∗ 200
o-Xylene A 35 ◦ C C o-Me−C6 H4 −CHO 45∗ 201
m-Xylene A 35∼40 ◦ C C m-Me−C6 H3 −CHO 35∗ 201
p-Xylene A 25∼30 ◦ C C p-Me−C6 H4 −CHO 68∼78∗ 201, 202, 205
p-Cymene A C Resin – 147, 200
A C p-MeO−C6 H4 −CHO 200
MeO C C Me
H H
A C 188
HO C C Me HO CHO
H H
MeO MeO
Naphthalene B B Naphthoquinone 189

Anthracene C B Anthraquinone 189
Note: Electrolysis Conditions: A MeCN−LiClO4 or Et4 NClO4 −(Pt); B H2 O/THF−H2 SO4 /MnO2 −(Pt)/Mn2 (SO4 )3 ;
C H2 O−H2 SO4 −(PbO2 /Pt)/Mn2 (SO4 )3
Mediator Systems: A [(L2 )2 MnO2 Mn(L2 )2 ](ClO4 )4 ; B Mn2 (SO4 )3 /(NH4 )2 SO4 ; C (NH4 )2 SO4
527
Tab. 11 Indirect electrooxidation with Mn(OAc)2 Mediator [194, 195, 206, 207]
Olefin Halide Product Yield

[%]
Me BrCCl3 Br 95
(CH2)5 Cl3C Me
(CH2)5
BrCCl3 CCl3 83
Br
BrCCl3 Br CCl3
60
N Ac
N
Ac
CBr4 Br CBr3 60
O
O
OAc CBr4 Br 96
Br3C OAc
Me Br2 CHCO2 Et Br Br 52
(CH2)5 Me
MeO2C (CH2)5
Me Br2 C(CO2 Et)2 MeO2C Br 61
(CH2)5 Me
MeO2C (CH2)5
B+
Me Br2 CF2 Br 40
Me
(CH2)5 BrF2C
(CH2)5
Me C8 F17 I I 80
(CH2)5 F3C(F2C)7 Me
(CH2)5
Note: Conditions: AcOH−AcOK/Mn(OAc)2 −(C)-(Stainless steel).
the electrolysis is not dangerous in the or methanol gives anisaldehyde (148) as

presence of organic materials and it is the major product together with a small
inexpensive. amount of the dimer (149). The oxida-
As a typical example of indirect elec- tion of p-methoxybenzyl methyl ether with
trooxidation of alkylbenzenes, the ox- CAN in methanol readily affords (148)
idation conditions and results on p- in 97% yields. The oxidation of p –t-
methoxytoluene (147) with CAN in butyltoluene (150) with CAN in methanol,
acetic acid or methanol are shown in however, results in only 10% yields of
Scheme 59 [219]. The treatment of (147) (153) along with the recovered (150) [219].
with CAN in methanol at room tempera- The desired oxidation of (150) is ac-
ture affords the aldehyde (148), exclusively. complished by treatment with CAN in
However, the oxidation of (147) with aqueous 50% acetic acid at 85∼90 ◦ C,
CAN in either aqueous 50% acetic acid giving (153) in 90% yield (Scheme 60). The
Tab. 12 Indirect electrooxidation of alkylbenzenes and hydrocarbons with cerium mediators
Substrate Electrolysis conditions Mediator Product Yield References

[%]
Toluene A A Benzaldehyde – 221–224

p-Chlorotoluene A A p-Chlorobenzaldehyde – 221
B 97 225
o-Chlorotoluene A B o-Chlorobenzaldehyde 99 225
p-Aminotoluene A A p-Aminobenzaldehyde – 221
p-Xylene A A p-Methylbenzaldehyde – 221–223
H2 O-H2 SO4 -(PbO2 ) A 70∗ 205
p-Methoxytoluene A A p-Methoxybenzaldehyde – 221, 223
H2 O/CH2 Cl2 -H2 SO4 -(Pt) A 94 226
B C 93∗ 219
H2 O-H2 SO4 -(?) A 72∗ 227
p-Cyanotoluene A A p-Cyanobenzaldehyde – 221
p-Isopropyltoluene C A p-Isopropylbenzaldehyde 90∗ 228
p-t-Butyltoluene B C p-t-Butylbenzaldehyde 90∗ 219
3,4,5-Trimethoxytoluene C A 3,4,5-Trimethoxy-benzaldehyde 93∗ 229
m-Phenoxytoluene H2 O-CF3 CO2 H-(Pt) D m-Phenoxybenzaldehyde 37 231
O C H2 O/MeOH-H2 SO4 -(Pt) B O CH 85 230
HC OH HO C H
HO C H O H C OH
HC OH HC OH
H C CH2OH
CH2OH
Note: Mediators: A Ce(SO4 )2 ; B Ce(MeSO3 )3 ; C CAN; D Ce(TFA)4 .

Electrolysis Conditions: A MeCN/H2 O-NaBF4 /H2 SO4 -(Pt); B H2 O/HNO3 -(Pt); C H2 O-H2 SO4 /PhH-(Pt).
529
O
OMe OMe OMe
or Me
Ce(IV) Ce(III)
Me CHO CHO
−e−
(147) (148) (149)
(148): 92% (in dry MeOH)
(149): 4∼18% (in wet MeOH)
Scheme 59 Selective side-chain oxidation of p-methoxytoluene with cerium (IV) as mediator.
AcOH/t-BuOH (10/1)-Et4NOTs-(C)
+
Cu(OAc)2
AcO AcO OAc

(151) 73% yield (152) 4∼18% yields
(150)
Aq. 50% AcOH- CAN/HNO3
90% yield
CHO
(153)
Scheme 60 Selective side-chain oxidation of 4 − t-butyltoluene with cerium (IV) as mediator.
electrooxidation of (150) in an AcOH-t- carbonyl compounds, that is, aldehydes,

BuOH(10 : 1)-Et4 NOTs-Cu(OAc)2 -(C) sys- ketones, and quinones [232–235]. Ceric
tem gives the two-electron oxidation ion can be regenerated electrochemically
product (151) (78% yield) together with at high current efficiency (95%). Re-
(152) (7%) [219]. Apparently, the actual sults are summarized in Table 13 [235,
path of the reaction depends strongly 236]. The larger scale production of
on the oxidation conditions and reac- naphthoquinone has been examined in a
tion media employed. Ceric trifluoroac- pilot plant [238].
etate in aqueous TFA is effective for
the oxidation of m-phenoxytoluene to m- 15.2.4.10 Copper (Cu) and Silver
phenoxybenzaldehyde [231]. (Ag)-assisted Oxidation
Methanesulfonic acid has been found The electrocatalytic oxidation of styrene
to solubilize the Ce(IV)/Ce(III) couple. with molecular oxygen in the presence of
This makes Ce-mediated electrosynthesis CuCl2 in an acetonitrile solution promotes
practical for the preparation of aromatic the C=C double-bond cleavage reaction
Tab. 13 Indirect electrooxidation of aromatic nuclei with cerium mediators
Substrate Electrolysis conditions Mediator Product Yield Refe-

[%] rence
Naphthalene H2 O-H2 SO4 -(Pb/Sb) Ce(SO4 )3 Naphthoquinone – 238

H2 O-HNO3 CAN/Ce(SO4 )3 70 236
1-Naphthol H2 O-H2 SO4 -(PbO2 /Ti) Ce(MeSO3 )2 Naphthoquinone – 237
NO2 H2 O-H2 SO4 -(Pb/Sb) Ce(MeSO3 )2 Naphthoquinone 94 232
Cl H2 O-H2 SO4 -(Pb/Sb) Ce(MeSO3 )2 O 99 232

Cl
O
H2 O-H2 SO4 -(Pb/Sb) Ce(MeSO3 )2 O 94 232
O
OMe H2 O-H2 SO4 -(Pb/Sb) Ce(MeSO3 )2 O 93 232
OMe
O
H2 O-H2 SO4 -(Pb/Sb) Ce(MeSO3 )2 O 94 232
O
Biphenyl H2 O-HNO3 CAN/Ce(SO4 )3 Ph 70 236
O O
Anthracene H2 O-MeSO3 H-(Pt/Nb) Ce(MeSO3 )2 Anthraquinone 95 232
H2 O-HNO3 CAN/Ce(MeSO3 )2 90 236
H2 O-HNO3 CAN/Ce(MeSO3 )2 O 65 236
to form benzaldehyde. It is found that a redox couple in aqueous chloride solutions

continuous addition of Cl− is required have been made.
to maintain the catalytic activity [239]. Electrochemically reduced copper (II)
Further extensions for the air-oxidation of sulfate activates dioxygen that reacts
benzene mediated with the Cu(I)/Cu(II) with benzene to afford phenol (26%),
hydroquinone (56%), and p-benzoquinone 2 A/dm2 at 25 ◦ C in 69∼99% current ef-

(43%) in good Faradaic yields [240]. ficiency [245]. 2-Butene can be efficiently
The epoxidation of alkenes is one of converted to 2-butanone in a two-phase
the most important oxidation methods. system consisting of 1,3-dichloropropane
Electrochemical epoxidation of electron- and aqueous Tl2 (SO4 )3 -H2 SO4 -(Pt) under
poor olefins such as enoates (154→155) vigorous stirring. Some typical results are
and enones has been accomplished by us- listed in Table 14 [246–248].
ing silver(III)oxo bis(2,2 -bipyridine) and
similar complexes (Scheme 61) [241]. (E)-
Dimethyl glutaconate is electrolyzed in 15.3
an MeCN-LiClO4 /AgOAc)(bpy)-(Pt) sys- Indirect Electroreduction
tem to give the trans-epoxide in 90%
yield. Mediators employed in electroreduction
The combination of anodic oxidation of media play an important role in indirect
benzene using the Ag(I)/Ag(II) mediator electroorganic synthesis. Surveyed here
with cathodic oxidation of benzene using are the reactions in which metal complexes
the Cu(I)/Cu(II) mediator in a single are used as electroreductive catalysts.
electrolytic cell produces p-benzoquinone Indirect electrochemical reactions usu-
selectively in both the anodic and the ally involve a multi-electron-transfer sys-
cathodic chambers [242]. Silver-mediator tem that consists of a set of electron
promoted electrooxidation of hydrocarbon transmission units (Fig. 4). Although the
has been attempted [243]. The kinetics of overall feature of an electron-transfer
indirect oxidation of catechol and L-dopa process in indirect electrosynthetic reac-
with IrCl6 2− has been studied in polymer- tions is understandable, each step of the
coated glassy carbon [244]. electron transmission has not yet been
elucidated [10].
15.2.4.11 Thallic Ion [Tl(III)]-assisted Indirect electroreductions use metal
Oxidation complexes, metal ions, and metal organic
Olefins that react with thallic ions may un- compounds as mediators. Their character-
dergo functionalization to 1,2-diols by oxi- istic features are well documented both
dation with electrogenerated Tl(III) to give in monographs [8, 11, 13, 15, 17] and re-
the carbonyl compounds and 1,2-diones. views [249–252]. This chapter reviews the
For this purpose, Tl(ClO4 )3 , Tl2 (ClO4 )3 , potential of such mediators for electrore-
and Tl(NO3 )3 can be used. The regen- duction, which involve recyclable metal
eration of Tl(III) can be carried out in a and nonmetal complexes, but not enzy-
Tl2 SO4 –H2 SO4 –(Pt) system at 3.3∼3.9 V, matic systems.
AgOAc(bpy)
O wet MeCN-LiClO4-(Pt) O O
87% yield
O O
(154) (155)
Scheme 61 Epoxidation of electron deficient olefins with silver complexes.

15.3 Indirect Electroreduction 533
Tab. 14 Conditions and results in indirect electrooxidation with Tl(III)
Substrate Conditions Mediator Product Ref-

(current efficiency, %) erence
Me CH CH2 TlClO4 /HClO4 -(Pt) Tl(ClO4 )3 Me CH CH2 Me C Me 246
OH OH O
Me CH CH Me TlSO4 /H2 SO4 -(Pt) Tl2 (SO4 )3 Me CH2 C(O) Me (97) 245
60 ◦ C
Cyclohexene TlClO4 /HClO4 -(Pt) Tl(ClO4 )3 Cyclopentane-1-carboxylic 247
acid, Cyclohexanone,
Cyclohexane-1,2-dione,
Cyclohexane-1,2-diol
Cyclohexane-1,2-dione TlClO4 /HClO4 -(Pt) Tl(ClO4 )3 C6 H8 O3 247
TlClO4 /HClO4 -(Pt) Tl(ClO4 )3 HO OH 247
C7H15 CH CH2 TlSO4 /H2 SO4 -(Pt) Tl2 (SO4 )3 C7H15 C Me (99) 245
60 ◦ C
O
TlNO3 + HNO3 Tl(NO3 )3 , CHO CHO 197

30 ◦ C
,
Fig. 4 Electron transfer Electron transfer

consists of a set of electron
transmission units. Electrode Mediator
Electron
transmission Mediator Mediator
units
Mediator Substrate
Indirect electroreduction with Ni, Co, complexes, which are relatively difficult to
and Fe complexes has been well stud- recycle, have also been used as mediators.
ied, and will be discussed first. Further-
more, the synthetic use of palladium, 15.3.1
rhodium, and ruthenium complexes as Indirect Reduction with Mediators
mediators in the electroreduction of or- Containing Nickel, Cobalt, and Iron
ganic compounds are finding increasing
applications. Metallic complexes derived 15.3.1.1 Nickel (Ni) Complex Mediators
from chromium, manganese, molybde- The electroreduction of Ni(II) complexes
num, tungsten, and rhenium have also to the corresponding Ni(0) complexes
been used as mediators for special con- has been investigated intensively. The
versions. Recently, tin, zinc, and mercury synthetic use of the Ni(0) complex
as a mediator has attracted the 2-halopyridines and aryl or heteroaryl

interest of numerous electrosynthetic halides catalyzed by Ni(bpy) complexes
chemists [253–257]. The electroreduction proceeds smoothly to give 2-arylpyridines
of Ni(II)L2 complexes [L = N ,N - in good yields [267]. The electroreductive
ethylenebis(salicylideneiminato)] to the coupling of phenyl halides is carried out in
corresponding Ni(I) complexes at a THF/HMPA(1 : 1)-LiClO4 system in the
an MeOH-(Pt) system has been presence of Ni(II)X2 L2 and an excess of
performed [257]. The Ni(I) complexes react ligand (L = phosphine ligand) to produce
rapidly with either alkyl bromides or Ni(I)XL3 (Scheme 62) [264]. The electrore-
alkyl iodides and the reaction leads to duction of [Ni(I)XL3 ]+ occurs at −1.9 V to
an alkyl radical, which gives a dimer give Ni(0)L4 and X− (Scheme 62). Oxida-
and regenerates the Ni(II) complex. tive addition of Ni(0)L4 to PhX smoothly
Controlled-potential catalytic reduction proceeds to yield PhNi(II)XL2 complexes
of 2-bromo- or 2-iodoethanol with (156) when an excess of PhX is present in
electrogenerated Ni(I) salen gives rise to the electrolysis medium (Scheme 63). The
the formation of 1,4-butanediol in 41% unstable complex PhNi(II)XL2 (156) un-
yield [258]. dergoes a two-electron reduction, which
Recently, chloro-, bromo-, and iodoben- liberates Ni(0)L4 , Ph− , and X− species.
zenes have been subjected to electrore- The regenerated Ni(0)L4 probably recycles
duction using Ni(0) complex mediators the process through the subsequent oxida-
to yield biphenyl. NiC12 L2 and NiBr2 L2 tive addition to PhX. The desired biphenyl
[L = P(Ph)3 , (Ph)2 PCH2 CH2 P(Ph)2 ] have is produced by the reaction of the complex
been used as catalysts [259–265]. Pro- (156) with Ph− in the presence of an excess
tic media such as alcohols, that is, amount of the ligand (L) and the subse-
methanol, ethanol or alcohol-water mix- quent reductive elimination of the Ni(0)
tures are found to be suitable solvents for species [265]. In the absence of the ligand,
achieving the electrosynthesis of biaryls an unstable low-valent Ni species can be
from aryl halides according to a pro- regenerated in a THF/HMPA (1 : 2) solu-
cedure that involves a catalytic process tion. Electrolyses in a mercury pool leads to
by nickel-2,2 -bipyridine complexes [266]. the following Faradaic yields of the dimer:
Electrochemical cross-coupling between 75% (from PhBr), 80% (from PhI), and
L e− e−, L
Ni(II)X2L2 [Ni(II)XL3]+ Ni(I)XL3 Ni(0)L4 + X -
−X−
Scheme 62 Electroreduction of nickel complexes.
Ni(0)L4
Ph Ph X− X− Ph−
PhX −L2
58∼82% yields
L (excess) 2e−
PhNi(II)XL2
L (excess)
(156) −2.2 V (Ag +/Ag)
Ph−
Scheme 63 Electroreductive coupling of aryl halides to biaryls.

Tab. 15 Electroreductive coupling of organic halides by using Ni complexes as mediators [268]
Substrate Electrolysis Conditions1 Mediator2 Product Yield References

[%]
t-Bu-Br THF/Bu4 NClO4 /(Au) (or EtOH) A n-C8 H18 15 269

PhX A B Ph-Ph 823 270–277
A B Ph-Ph 754 259–265, 268, 274–279
A A Ph-Ph 805 259–265, 268, 274–279
EtOH/Bu4 NX/(Au) (or LiX) C NiBr2 dppe Ph-Ph 5∼6 274–277
DMF/HMPT/LiClO4 /(Hg) B Ph-Ph 80 280
PhCH2 Cl A B (PhCH2 -)2 95 270, 278
4-MeC6 H4 Br B B (4-HMeC6 H4 -)2 75 280
4-MeC6 H4 Cl A B (4-MeC6 H4 -)2 57 270–273
3-MeC6 H4 Cl A B (3-MeC6 H4 -)2 70 270–273
4-MeOC6 H4 Br B B (4-MeOC6 H4 -)2 36 280
4-AcC6 H4 Br B B (4-AcC6 H4 -)2 47 280
4-MeO2 CC6 H4 Cl B B (4-MeO2 CC6 H4 -)2 51 280
4-PhC6 H4 Cl A B (4-PhC6 H4 -)2 71 270–273
1 Electrolysis Conditions: A NiBr2 (PBu3 )2 ; B NiCl2 (PPh3 )2 ; C NiBr2 (PPh3 )2 .

2 Mediators: A THF/HMPT/LiClO4 /(Hg); B DMF/Bu4 NBr/(Pb); C NiBr2 (PPh3 )2 .
3X = Cl.
4X = Br.
5 X = I.
15.3 Indirect Electroreduction
535
95% (from PhCl). However, the turnover coupling of any halide. Poly(N -ethyl-3,6-
is estimated to be less than 10 times be- carbazolediyl) is synthesized from 3,6-
cause the Ni(II) salt is partially hydrolyzed dibromo-N -ethylcarbazole by electrore-
into Ni hydroxide during the electrolysis. duction in a DMA-LiBF4 /NiBr2 (bpy)-
Addition of hydrochloric acid or perchlo- (Mg/Hg) system at −1.3 V (SCE) [283].
ric acid allows the regeneration of the The electroreductively produced ArNi(II)
electroactive Ni(II) species and the elec- XL2 (162) can lead to the corresponding
trolysis can be conducted continuously. A aryl-carboxylates (163) [284]. Electroreduc-
survey of the Ni(0) complex-assisted reduction of the arylnickel complexes (162),
tive dimerization of aryl halides is collected formed by insertion of an electrogenerated
in Table 15 [268]. [Ni(0)L2 ] into aryl halide (161) (X = Br, Cl)
Poly(1,4-phenylene) polymers (158) are in the presence of CO2 in a THF/HMPA-
prepared by the electroreduction of aryl LiClO4 (or Bu4 NBF4 ) system, affords the
halides (157) in a THF/HMPA(3/1)- carboxylate (163) (Scheme 66) [271–273].
LiClO4 (or Bu4 NBF4 )-(Li/Hg) system with The mechanism of the chain reaction,
NiCl2 (dppe) complex as a catalyst leading to benzoic acid has been inves-
(Scheme 64) [281]. The electroreduction of tigated on the basis of a detailed kinetic
1,4-dichlorobenzene (159) in the pres- analysis of the propagation of this catalytic
ence of Ni(II)(dppe) complexes in a chain and of its competition with the chain
DMSO-Bu4 NBF4 -(C) system proceeds to leading to biphenyl [278].
give polymers (160) in a high yield Electrocarboxylation of benzylic chlo-
(Scheme 65) [270]. Poly(2,5-pyridine) films rides has been intensively investigated
are deposited on glassy carbon, plat- in the presence of a Ni(II) complex as
inum, and gold electrodes by electrore- a catalyst [274–277]. Fenoprofen (165),
duction in the presence of Ni[(PPh3 )]4 an anti-inflammatory agent, is electrosyn-
catalysts [282]. The dichloro(1,2-bis(di-2- thesized from (164) in a THF/HMPA-
propylphosphino)benzene)nickel(II) plays Bu4 NBF4 -(C/Ni) system in the presence of
a role as an electrocatalyst for the reductive NiCl2 (dppp) as a mediator under bubbling
THF-HMPT(3 : 1)-LiClO4-(Li/Hg)
Br Br + 2nX−
2ne−, −2.5 V (Ag/Ag +)
m n
NiCl2(dppe)
(157) m = 1, 2 (158)
n = 9∼10 79% yield
4∼16 80%
Scheme 64 Poly(1,4-phenylene) polymers by electroreduction of aryl halides.
−2.2 V
Cl Cl
DMSO, 65 °C
x
(159) (160)
Scheme 65 Electroreduction of 1,4-dichlorobenzene to poly(1,4-phenylene).

CO2, 2e −
R X R Ni(II)XL2 R CO2−
−X−
(161) (162) (163)
[ Ni(0)L2 ] 57∼86% yields
X = Br, Cl
R = F, PhO, CF 3
Catalyst: NiCl 2(dppe)2, NiCl2(PPh3)2, NiCl2(PPh3)2
Scheme 66 Nickel-catalyzed carboxylation of aryl halides.
O O
H H
THF/HMPA-Bu 4NBF4-(C/Ni)
C Cl C CO2H
CO2, NiCl2(dppp), 85% yield
Me Me
(164) (165)
Scheme 67 Electrocarboxylation of benzylchlorides.
Ph Ph Ph
Cl
NiCl2[P(C6H5)3]2 O + O
R1 N O DMF/Bu4NBr/(Pb) R1 N R1 N
R2 R2 R2
(166) (167) (168)
Scheme 68 2-Oxindol derivatives by nickel-catalyzed cyclization of aryl halides.
CO2 (Scheme 67) [277]. Recently, the com- DMF-Bu4 NBr-(Pt/Pb) system at 60 ◦ C ini-
bination of a new electrolyzer for organic tiates the cyclization through its insertion
solvents and oxidation of metal powder as into the Ar−Cl bond of (166). The sub-
an alternative to sacrificial anodes has been sequent carbometallation followed by the
developed [269]. electroreductive elimination of the Ni(0)
Electroreduction of benzyl bromide with complex by warming up to 70 ◦ C gives
Ni(I) complexes provides different prod- (167) (55%) and (168) (8%) [279].
ucts depending on the reduction poten- Cyclopropanation of a tandem-radical
tials: potential (V vs. Ag/Ag+ in MeCN) [2 + 1] cycloaddition occurs by a Ni comp-
−1.45 bibenzyl 76%, toluene 2%; −1.80 lex-catalyzed electroreduction of 2-bromo-
bibenzyl 7%, toluene 90% [280]. or 2-iodo-1,6-diene derivatives [285].
The synthetic utility of Ni(II)Cl2 L2 The electroreductive cyclization of the
[L = P(Ph3 )] as a mediator has been halogenated ether (169) or a halo-
shown in the preparation of 2-oxyindole genated ester using Ni(II) complexes
derivatives (167) and (168) (Scheme 68). (171) and (172) proceeds in the manner
First, the Ni(0) complex produced in a shown in Scheme 69 [286]. The radical
2+
Br N N
Ni (ClO4−)2
Ni(I) Ph
O N N (171)
Ph
−0.95 V (SCE)
(169)
+e− −Br −
2+
Ni(II) N N
Ph
O Ni (ClO4−)2
Ph
N N
Cathode (172)
(170)
−1.16 V (SCE)
Scheme 69 Nickel-catalyzed cathodic cyclization of unsaturated ethers.
Ph(CH2)3Br
(173) DMF-Et4NClO4/NH4ClO4-(C)
+ Ph(CH2)3CH3CH2CN
Ni complex, 72% yield
H2C CHCN (175)
(174)
Scheme 70 Cathodic coupling of 3-phenylpropylbromide with acrylonitrile.
O O
Br DMF-Et4NClO4-(C)
86% yield
E
E
(176) (177)
Ni(tet)(ClO4)2: 5,7,7,12,14,14-hexamethyl-1,4,8,11-
tetrazocyclotetradecane nickel(II) perchlorate
Scheme 71 Cyclization of vinylbromide 176 to bicyclic compound 177.
cyclization in a DMF-Et4 NClO4 -(C) sys- electroreductive arylation of conjugated es-

tem affords the tetrahydrofuran (170) in ters using a Ni salt as a catalyst takes
53∼58% yield. The electroreductive in- place to yield β-arylpropionates in a mod-
termolecular addition of alkyl radicals to erate yield [288]. Intramolecular cycliza-
conjugated systems has been achieved tion of the vinyl bromide (176) to the
using a Ni(II) complex as an electron- bicyclo compound (177) proceeds in a
transfer catalyst [287]. The coupling reac- DMF-Et4 NClO4 -(C) system in the pres-
tion of 3-phenylpropyl bromide (173) with ence of a Ni(tet)(ClO4 )2 complex in 86%
acrylonitrile (174) is carried out in a DMF- yield (Scheme 71) [289]. The in situ elec-
Et4 NClO4 /NH4 ClO4 -(C) system to give the trogenerated Ni(I) salen complex is found
adduct (175) in 72% yield (Scheme 70). The to be an effective catalyst for reductive
Ar 2e−
Ar X R CH CH Ar
(178) L Ni 50∼80% (182)
yields
+ R
X + HX
R CH CH2 (180)
L = PPh3
(179) Ni(0)L2
R = H, Ph
X = Cl, Br, I (181)
Scheme 72 Nickel-catalyzed coupling of aryl halides and alkenes.
Anode: Al Al3+ + 3e−

(a)
Cathode:
2e−, Ni
Ar X + R CHCO2Me R CHCO2Me + X− + Cl −
(183) (184)
(b) Cl Ar
Slow
Ni(II) + 2e− Ni(0) ArNiX
(c) −1.2 V vs. SCE Ar X
Fast
Ni(0) + RCHXCO2Me RCH(NiX)CO2Me
(d) (185) (186)
+AlX3 +ArNiX
(186) RCH(AlX2)CO2Me (184) + AlX3 + Ni(0)
−NiX2
(e) (187)
Scheme 73 β,γ -Unsaturated esters by coupling of α-chloroesters with vinyl or aryl halides.
intramolecular cyclization of 6-iodo- and in a few minutes to give the substituted

6-bromo-1-phenyl-hexynes to yield ben- olefins (182). If triethylamine is added
zylidenecyclopentane in 84% yield [290]. as a base together with the aryl halide,
The reactivity of Ni(0)(bpy) complexes to- the yield of the cross-coupling product is
ward organic halides (RX: PhI, PhCH2 Cl, almost doubled [292]. Ni(II)-catalyzed in-
4-MeOC6 H4 Br, C6 H13 Br, and so on) tramolecular cyclization of o-halogenated
are shown to be dependent on the aromatic compounds proceeds in 30∼90%
amount of the ligands present in an N - yield [293].
methylpyrrolidone solution [291]. β, γ -Unsaturated esters (184) have been
A new catalytic coupling of aromatic synthesized by a one-step electrochemical
halides (178) and alkenes (179) has been procedure from α-chloroesters (183) and
developed using σ -arylnickel complexes aryl or vinyl halides (Scheme 73b) [294,
(180) (Scheme 72) [292]. The coupling re- 295]. This novel electroreductive cross-
action can be realized in a THF/HMPA- coupling method is based on the use of
LiClO4 -(Au) system at 25∼50 ◦ C. The σ - a Ni(II)(bpy) catalyst and a sacrificial alu-
arylnickel complexes (180) obtained are minum anode in a one-compartment cell
stable enough to be detected (reduction at (Scheme 73). The whole cathodic process
−1.3 V vs. SCE); however, they decompose progresses at −1.2 V (SCE) (Scheme 73c),
and the reaction sequence is shown been accomplished in ethanol by the

in Schemes 73(c∼e), including the key use of Ni(II)(bpy) complexes as a
step (Scheme 73e) that allows the recy- catalyst [298]. 2- or 3-bromothiophenes
cling of the catalyst. The electroreductive are efficiently coupled with activated
intermolecular coupling of aryl halides alkyl chlorides (α-chloroesters, α-
(178) with α-chloroketones (188) has also chloroketones, α-chloronitriles), benzyl
been attained in a DMF-Bu4 NBF4 -(Al/Ni chloride or vinyl halides, in a one-
or Zn/C) system in the presence of a step electrochemical reaction, using
catalytic amount of a Ni complex to a sacrificial anode and Ni(II)(bpy)
give the product (189) in 40∼70% yield complexes [299, 300].
(Scheme 74) [296, 297]. Some results are The electrosynthesis of homoallyl
shown in Table 16. alcohols (193) or β-hydroxy esters (196)
The conjugated addition of aryl has been carried out by the reaction of
bromides to activated olefins has methallyl chloride (190) (Scheme 75) or
DMF-Bu4NBF4 -(Al/Ni)(or Zn/C)

Ar X + ClCH2COMe Ar CH2COMe
NiBr2(bpy), 40∼70% yields
(178) (188) (189)
Ar = aryl, pyridyl, naphthyl, etc.
Scheme 74 Coupling of aryl halides with α-chloroketones.
Tab. 16 Nickel-catalyzed electroreductive coupling of α-chloroesters with aryl and

vinyl halides1 [294]
ArX Chloroester Coupling

product2 yield
[%]
Bromobenzene MeCHClCO2 Me (50) 40

Iodobenzene ClCH2 CO2 Me (20) 70
p-Methoxyiodobenzene MeCHClCO2 Me (20) 85
4-Bromotrifluoromethylbenzene MeCHClCO2 Me (20) 66
4-Bromocyanobenzene ClCH2 CO2 Me (20) 60
MeCHClCO2 Me (20) 70
1-Methylnaphthalene MeCHClCO2 Me (20) 80
1-Bromonaphthalene MeCHClCO2 Me (20) 40
Br MeCHClCO2 Me (20) 45
MeO
2-Bromothiophene MeCHClCO2 Me (20) 40
ClCH2 CO2 Me (20) 55
CH CHBr
MeCHClCO2 Me (20) 60
1 Carried out in a DMF-Bu4 NBr/NiBR2 /2,2-Bipyridine-(Al/C) system.

2 Based on initial ArX.
R1
O (192)
R2
2e−
R1 OH
Cl NiL2Cl R2
(190) (191) (193)
Ni(0)L2 Cl − 50∼90% yields
R1 = Ph, C6H13, Ph, 2-Furyl

R2 = Me, H, H, H
Scheme 75 Homoallyl alcohol by nickel-catalyzed addition of methallyl chloride to carbonyl
compounds.
R1 R1 OH
2e−
ClCH2CO2Me + O CO2Me
cat-NiBr2bpy
R2 R2
(194) (195) (196)
R = Et, Pr, Me 2C = CH(CH2)2, t-Bu, Ph
1
60∼86% yields
R2 = Me, Et, Ph
Scheme 76 β-Hydroxyester by nickel-catalyzed addition of methyl chloroacetate to carbonyl
compounds.
methyl chloroacetate (194) (Scheme 76) transient alkyl-Ni(III) complexes has been
with carbonyl compounds (195) in a DMF- reported in the electrochemical reduc-
Bu4 NBr-(Zn/C) system in the presence tion of Br(CH2 )4 CN mediated by the
of the Ni(II)Br2 (bpy) complex as a Ni(II) macrocycle, (R,R,S,S)-Ni(tmc) [306],
mediator [301, 302]. An electrochemical, of methyl iodide with Ni(I)(OEiBC) [305],
Ni(0)-catalyzed Reformatsky reaction of of butyl bromides [280], and of alkyl bro-
methyl chlorodifluoroacetate and carbonyl mides with a cyclic tetraamine complex of
compounds has been performed in Ni(II) [307].
a one-compartment cell using a The electrosynthesis of bicyclic ke-
zinc anode to give 2,2-difluoro-3- tones (198) has been performed by the
hydroxyesters in 45∼77% yields [303]. reduction of bromoalkylcyclohexenones
Allylation of benzoic anhydride with alkyl using Ni(II) complexes as mediators.
bromide is performed in an HMPA- The electrochemical Michael-type addi-
Bu4 NClO4 -(Pt) using 10 mol% of NiBr2 - tion (197)→(198) can be attained in
(bpy) [304]. a DMF-NH4 ClO4 /Et4 NClO4 -(C/C) system
It is known that the [Ni(I)(OEiBC)]− in the presence of Ni(cyclam)(ClO4 )2
complex mediates electrocatalytic reduc- as a redox mediator at −1.8 V (SCE)
tions of alkyl halides and methyl p- (Scheme 77) [308].
toluenesulfonate [305]. The nucleophilic- Olefin dimerization (200→201) cat-
ity of the Ni(I) complex is comparable alyzed by electrogenerated Ni(I) complexes
to that of the ‘‘supernucleophile’’ vi- is performed in a PC-Bu4 NClO4 -(Zn) sys-
tamin B12 . Recently, the formation of tem in the presence of an Ni(II)Cl2 (PPh3 )2
Br
O O O
(CH2)n (CH2)n H
DMF-NH4ClO4/Et4ClO4-(C/C)
(CH2)n +
Ni(II)/Ni(I)
(197) (198) (199)

70% yield 6% yield
Scheme 77 Intramolecular cathodic Michael-type addition.
PC-Bu4NClO4/Ni(II)Cl2(PPh3)2 -(Zn)
CH3 CH CH2 Dimers
4-methyl-2-pentene : 41.8%
(200) 2-methyl-2-pentene : 22% (201)
2-methyl-1-pentene : 16%
2-hexene : 23.4 %
Scheme 78 Nickel-catalyzed cathodic olefin dimerization.
CH2 CH2
Ar X ArNiL2X Ar CH CH2
e−
−1.3 V (203)
(202) Ni(0)L2
2e− −0.9 V (SCE) L = PPh3
Ni(II) + L
Scheme 79 Addition of nickel(0)-complexes to ethylene.
complex (Scheme 78) [309]. The electroly- the absence of an olefin, the electroreduc-
sis is carried out in a one-compartment tion of Ni(II) successively gives Ni(I) and
cell with a sacrificial anode (Zn, Cd, then Ni(0) of the type Ni(0)L3 , whereas,
Al, and so on). The oxidative addition in the presence of an olefin, for example,
of the electrogenerated Ni(0) complexes ethylene, the total reduction of Ni(II)X2 L2
to aryl halides (202) yields (203); the can be attained in the absence of added
reaction is influenced by the concen- L, leading directly to the Ni(0) species
trations of the ligands triphenylphos- such as Ni(0)L2 C2 H4 . These zero-valent
phine, halide ion, and triethylamine complexes probably exist as an anionic
(Scheme 79) [310]. The electrochemical be- form Ni(0)L3 X− and Ni(0)L2 C2 H4 X− de-
havior of Ni(II)X2 L2 (X = Cl, Br, I; L = pending on the nature and concentration
PPh3 ) in N -methylpyrrolidinone is af- of X− [311]. The electrogenerated cationic
fected by halide salts (X− ), by the con- Ni(I) complexes may act as an isomer-
centration of the ligand, and the presence ization catalyst for alkenylbenzene. The
of olefin [311]. The electroreduction of the [Ni(I)(PPh3 )4 ]+ complex is prepared di-
Ni(II) species can lead to soluble Ni(0) rectly by one-electron reduction of the
complexes only when the Ni(II) reagent parent Ni(II) perchlorate in an MeCN-
is complexed by both PPh3 and X− . In Bu4 NClO4 -(C/C) system [312].
R1 R1
*
R1 R2 + CO2 R2 H + R2 CO2H
CO2H H
(204) (205) (206)
* = DMF-Bu4NBF4-(Mg/C)
Scheme 80 Electrocarboxylation of diynes.
CO2H
1) NiBr2L2 -PMDTA CO2H
Ph + CO2
Ph
2) H3O+
(207) (208) 85% yield
Scheme 81 Cathodic biscarboxylation of styrenes.
Ni(II) associated with PMDTA (2,5,8- carboxylated to give mono- or dicarboxylic

trimethyl-2,5,8-triazanonane) is found to acid derivatives (208) in 85% yield, depend-
be a catalyst precursor for the incorpora- ing on the alkene structures (Scheme 81).
tion of CO2 into alkynes in an electrolysis The proposed catalytic cycle for the nickel-
using a dissolving Mg anode [313, 314]. catalyzed electrocarboxylation of alkenes
Different carboxylic acids are formed de- (209) is shown in Scheme (82) [320]. The
pending on the nature of the auxiliary electrolysis is performed in a DMF-
ligand [315]. The incorporation of CO2 Bu4 NBF4 /Ni(bpy)3 (BF4 )2 -(Mg/C) system
into alkynes catalyzed by electrogenerated in an undivided cell under a CO2 atmo-
Ni(bpy) complexes using a sacrificial Mg sphere (1 atm). In the presence of Mg(II),
anode gives α,β-unsaturated acids in mod- the intermediates (210) and (212) are con-
erate to good yields [316]. Recently, the first verted to magnesium carboxylates (211)
example of direct CO2 incorporation into and (213) together with Ni(II). These car-
conjugated 1,3-diynes has been reported. boxylates, which accumulate during the
The electrosynthesis of 2-vinylidene-3-yne course of the reaction, are a stable species.
carboxylic acids (205) and (206) from A tandem cyclization–carboxylation of
CO2 and substituted 1,3-diynes (204) is unsaturated haloaryl ethers has been
attained in a DMF-Bu4 NBF4 -(Mg/C) sys- investigated by electrogenerated Ni com-
tem by using a nickel-triamine complex plexes [321]. 2-Bromomethyl-1,4-dibromo-
as the catalyst and results in a regio- and 2-butene undergoes electroreductive car-
stereoselective addition to one triple bond boxylation under CO2 atmosphere in
(Scheme 80) [317, 318]. The simultaneous a DMF-Bu4 NI-(Ni)-(Pt) system to af-
activation of CO2 and diynes by electrogen- ford 3-methylene-4-pentenoic acid in 57%
erated Ni(0)(bpy) complexes enables the yield [322]. The electrocarboxylation of
selective incorporation of one molecule vinyl bromides under CO2 has been per-
of CO2 into unsaturated systems and the formed in a DMF-BU4 NBF4 -(Mg)-(Pt) sys-
preparative-scale electrosynthesis of car- tem, giving the corresponding acids in
boxylic acids [319]. The electrogenerated good yields [323].
Ni(0)(bpy) complexes can also be used for Raney nickel(W-2) covering the Ni elec-
the electrochemical incorporation of CO2 trode has been found to be an effec-
into C−C double bonds. Olefins (207) are tive catalyst under normal pressure and
L, 2e− (cathode)
H CO2− Mg +2
Ni(II)
(211) L Ni(0)
Mg − 2e− Mg+2 H+ L Ni O
anode (solvent) O
(210)
CO2
O
O (209)
L Ni
CO2− CO2−
O
Mg +2
O
(213) (212)
Scheme 82 Catalytic cycle of carboxylation of alkenes.
at room temperature for the electrocat- catalytic process [325]. The Ni(0)(bpy)2
alytic reduction of unsaturated functional complex (225) formed at −1.2 V (SCE)
groups such as C=O, C=N, C≡N, C=C, reacts stoichiometrically with CO2 to yield
C≡C, and N=O bonds [324]. The reduc- the stable Ni(0)(bpy)(CO2 ) complex (225)
tion is carried out in an MeOH-MeONa (Scheme 83b). The concentration of the
system and the discharge potential of Ni(0) species (225) and (216) is deter-
this system is −1.0 V (SCE) in contrast mined by the Scheme (83c). The various
to the potential of −1.5 V at a nickel- steps of the Ni(II)bpyX2 (214)-catalyzed
plated cathode. The use of transition-metal electrosynthesis of ketones (221) from
complexes as electrocatalysts, however, halides (217) and CO2 are summarized
can shift this negative potential toward in Scheme (83a). Ketones can also be read-
the positive side. The electroreduction ily obtained by the electroreduction of an
of an Ni(bpy) complex, in the presence organic halide in the presence of metal
of CO2 in N -methylpyrrolidone (NMP) carbonyls and NiBr2 (bpy) complexes in
or DMF as a solvent gives the corre- DMF [326]. Catalytic CO2 incorporation
sponding Ni(0) complex (225) associated into epoxides has been realized by the use
with two molecules of CO (Scheme 83b). of Ni(II)(cyclam) [327]. The dissolution of
Symproportionation with (215) leads to a stainless steel anode provides catalytic Ni
(216) (Scheme 83c). Oxidative addition species that enable the efficient synthesis
of an alkyl halide to (216), followed of ketones by electrolysis of organic halides
by an internal CO shift and reduc- in DMF in the presence of bipyridine
tive elimination, leads to the formation and CO [328]. Electro-assisted synthesis
of Ni(II) and the symmetrical ketone of 2-chlorobenzal bromide has been con-
(221) in high yield (Scheme 83a). The ducted in a DMF-Bu4 NBr-(Cu/Ni) system
Ni(0) species is electrochemically regen- in the presence of 1,2-dibromoethane and
erated, thus giving rise to an efficient 1,10-phenanthroline monohydrate in an
[Ni(II)(bpy)2] 2+ (214)
R CO R e−
(221)
Ni(0)bpy 2
(215) CO2
R C Ni(bpy)R R COX
R = Aryl (224)
(220) Ni(0)bpyCO Vinyl
O R = alkyl (216) R C NibpyX
RX (217) (223)
R2Nibpy (CO)
O
(219) Unstable Stable
R Ni bpy(CO) X
(a) Ni(II)bpyX2 (222) (218)
−1.2 V
[Ni(II)(bpy)2]2+ + 4CO2 + 6e− Ni(0)bpy(CO)2 + 2CO32−
(b) (214) (225)
(225) + Ni(0)bpy2 2Ni(0)bpyCO + bpy

(c) (216)
Scheme 83 Nickel-catalyzed formation of ketones and acid halides from carbon dioxide and aryl or
vinyl halides.
H2O/KNO3/(Hg)/NiCl2(cyclam)
−1.00 V (NHE), pH 4.1, 25 °C
CO2 CO
Current efficiency 99%
Scheme 84 Cathodic reduction of carbon dioxide to carbon monoxide.
undivided cell, yielding the desired prod- at relatively low potentials. However, the
uct in 90% yield [329]. current yield and turnover numbers need
The electrocatalytic reduction of CO2 to be improved. Metal phthalocyanines
is important not only for alternative fuel are also used as electrocatalysts [339].
sources but also for the storage of electric The direct conversion of CO2 to
energy. The direct electroreduction of methane, using Ru complexes as
CO2 to CO requires a large negative electrocatalysts, is also a very interesting
potential (e.g. in DMF, −2.21 V and research subject [340]. A comparison of
in MeCN, −2.10 V vs. SCE) [330]. Many the CO2 reduction potential observed
efforts have been made in search of on different electrodes together with
significant metal-complex (or cluster) thermodynamic potentials, E0 , is given
catalysts for the reduction of CO2 . in Fig. 5 [341]. Some results obtained
Nickel, Co, Fe, Re, Ru, and Rh-metallic by electroreduction of CO2 in the
complexes have all been used for this presence of Ni complexes together
purpose. Among them, NiCl2 (cyclam) with other mediators are presented in
(Scheme 84) [331–335], [Fe4 S4 (SR)4 ]2 − Table 17 [342–344].
[336], Re(bpy)(CO)3 Cl [337], and Ru(trpy) The electrocatalytic reduction of nitrous
(dppene)Cl+ [338] complexes turn out to oxide to dinitrogen has been achieved at a
be efficient homogeneous catalysts for mercury electrode using Ni(II) complexes
the selective reduction of CO2 to CO of macrocyclic polyamines [355].
HCOOH Pb CO2 + 2H+ + 2e− HCOOH
Sn
CH3OH Cu CO2 + 6H+ + 6e− CH3OH + H2O
Hydrocarbon Cu CO2 + 8H+ + 8e− CH4 + 2H2O

(CH4, C2H4, etc.) 2CO2 + 12H+ + 12e− C2H4 + 4H2O
CO Ni(II)cyclam CO2 + 2H+ + 2e− CO + H2O
Au
Co(II)Pc/C
CoTPP-py-GC
E o(CO2 /HCOOH) −0.196

E o(CO2 /CO) −0.106
−1.5 −1.0 −0.5 0 0.5

E (RHE) E o(CO2/CH4) 0.169
o
[V] E (CO2/CH3OH) 0.022
Fig. 5 Comparison of carbon dioxide reduction potentials observed on different

electrodes together with thermodynamic potentials, E◦ .
O OH
DMF-Bu4NBF4 -(Mg)
[Ni(bpy)3][BF4]2, 99% yield
CN CN
(226) (227)
Scheme 85 Cleavage of an aryl allyl ether for deprotection of a phenol.
Nickel-catalyzed electroreductive cleav- example, the electrolysis of 2-cyanophenyl

age of the carbon–oxygen bond of allyl allyl ether (226) has been electrochemically
ethers has been reported [356]. The influ- deprotected in the presence of a Ni catalyst,
ence of the nature of the ligands associ- Ni(bpy)3 (BF4 )3 to give the phenol (227) in
ated to the Ni center tends to determine quantitative yield (Scheme 85) [358].
the chemoselectivity of the above reac- The electroreductive dehalogenation
tion [357]. of gem-dichlorocyclopropane derivatives
The cationic complex [Ni(bpy)3 ](BF4 )2 (228) to the monochloride (229) has been
is a good catalyst for the electroreductive performed by electrolysis in a DMF-
cleavage of the C−O (allyl) bond of allyl Bu4 NI-(Hg/Cu) system at −0.5 V (SCE)
ethers, affording parent alcohols or phe- in the presence of Ni(II)(BF4 )2 • 6H2 O
nols. The Ni(II)-catalyzed electroreductive (or Co(II)(BF4 )2 • 6H2 O) and anthracene
deprotection of allyl ethers is found to pro- (Scheme 86) [359]. An intramolecular
ceed in a DMF-Bu4 NBF4 -(Mg) system. For propargyl transfer reaction has been
Tab. 17 Electroreduction of carbon dioxide with mediators
Electrolysis conditions Mediator Current Turnover Reference

efficiency [%] No/h
(product ratio)
H2 O/KNO3 /(Hg) −1.0 V vs. NHE NiCl2 (cyclam)a 99 (CO) 32 332

H2 O/NaClO4 /(Hg) −1.4 V vs. SCE Ni(II)(cyclam)a . . . (CO) ... 342
H2 O/MeCN(2 : 1)/LiClO4 /(Hg) −1.6 V vs. SCE Ni(tamc)b 98 (CO/H2 , 2 : 1) 6 335
TMU/Bu4 NBF4 /(C/Ni)c Zn(powder) or Mg(turnings) NiCl(dppp) 85 ∼ 96 (R-CO2 − ) ... 269
MeCN H2 O/Bu4 NClO4 /(Pt) −0.8 ∼ 1.3 V vs. SCE [(Me6 [14]ane N4 )Ni(II)]2+ 95 ∼ 100 (CO) ... 343
H2 O/Clarks-Lubs buffer/(Hg/Pt) −1.2 V vs. SCE Co(tsp)d or Ni(tsp) ... ... 333
H2 O/MeCN(2 : 1)/KNO3 /(Hg) −1.6 V vs. SCE Co(tamc)b 90 ∼ 93 (CO/H2 , 1 : 1) 78 335
H2 O/Clark-Lubs buffer/(Hg) 1.1 ∼ 1.5 V vs. SCE Co(tcpp)e ) . . . (formate) ... 344
DMF/Bu4 NBF4 /(Hg) −2.0 V vs. SCE [Fe4 S4 (SR)4 ]2− (R = Ph,PhCH2 ) 93 (formate) ... 336 345
H2 O/KCl/(Pt) −0.6 V vs. SCE K2 Fe(II)[Fe(II)(CN)6 ] 100 (CO → MeOH) ... 346
DMF/H2 O(9 : 1)/Et4 NCl/(C) −1.2 vs. NHE Re(bipy)(CO)3 Cl 98 (CO) 300 337
MeCN/Bu4 NPF6 /(Pt) −1.4 V vs. SCE Ru(trpy)f (appene)Cl+g . . . (CO) ... 338
H2 O/DMF/NaOH/H3 PO4 −1.50 V vs. SCE [Ru(bpy)2 (CO)2 ]2+ (pH 6: CO, formate) ... 347 348 349
(pH 9: CO)
H2 O/Na2 SO4 /KHCO3 −0.9 V vs. Hg2 SO4 , pH 4 RuO2 /TiO2 (35/65) (electrode) 76 (MeOH) – 350
MeCN/Bu4 NClO4 /Me2 NH/Me2 NHHCl/(Hg) −1.30 V [Ru(bpy)2 (CO)2 ]2+ 75.7 (formate) 21.4 (DMF) 351
vs. SCE
MeCN/Bu4 NPF6 /(Pt) −1.55 V vs. SSCE cis-Rh(bpy)2 h (CF3 SO3 )2 64 (formate) – 338
H2 O/Et4 NClO4 /(C) −0.8 V vs. Ag/Ag+ Rh(bpy)3 Cl3 25 (formate) – 347
CH2 Cl2 /Bu4 NBF4 /(Pt) −1.50 ∼ −1.65 V (Ag/Ag+ ) Pd(oep)i – 352
– (oxalate)
MeCN/Bu4 NClO4 /(Pt) −1.55 V vs. SSCE poly-Re(vbpy)(CO)3 Cl 92.8 (CO) 516 353
MeCN/Bu4 NPF6/(Pt) −1.50 ∼ −1.55 V vs. SCE fac-Re(bpy)(CO)3 Clh 85 (CO) 20∼30 354
a cyclam: 1,4,8,11-tetraazacyclotetradecane f trpy: 2,2 ,2 -terpyridine

b tamc: tetraazamacrocyclic complexes g appene: cis 1,2-bis(diphenylphosphino)ethylene
c TMU: tetramethylurea h bpy: 2,2 -bipyridine
d tsp: 4,4 ,4 ,4 -tetrasulfonated Phthalocyanine i oep: 2,3,7,8,12,13,17,18-octaethylporphyrin.
15.3 Indirect Electroreduction
e tcpp: mesotetracarboxyphenylporphine
547
Me CO2Me Me CO2Me
DMF-Bu4NI-(Hg/Cu)
Cl Cl
−0.5 V (SCE), 70% yield
Cl H
(228) (229)
Br
H2O + Me Me Me
Me
H2NOC Me CONH2 Me
Me
Me Me N Me
Me N
HO N
H2NOC N Co
N N Me
Me CONH2 Me N N
Co
H Me Me Me
H2NOC N N
Me Me Me (231)
Me
Me
Br
Me Me CONH2
O Py
N+ Me H
NH O O−
H3C N Me Me N N Me
HO H
O H Co
H O N N
P H Me Me
(230)
−O O −O O
H (232)
O OH H
Cl
Scheme 86 Dehalogenation of gem-dichlorocyclopropane derivatives.
attained by Ni complexes [360]. Cyclic non-micelle-forming surfactant to give the

sulfides have been synthesized by the corresponding alcohols as major prod-
Ni complex-catalyzed electroreduction of ucts [365]. Palladium on Ni in methanol
unsaturated thioacetates and thiosul- is found to be a very effective and highly
fonates [361]. selective cathode for the electrocatalytic
The hydrogenation of styrene into ethyl- hydrogenation of nitrobenzenes to ani-
benzene using a two-compartment cell lines [366].
separated by a hydrogen-permeable sheet
prepared from LaNi5 has been investi-
gated [362]. Electrocatalytic hydrogenation 15.3.1.2 Cobalt (Co) Complex Mediators
of conjugated enones to the corresponding Vitamin B12 derivatives and their model
carbonyl compounds has been achieved compounds have recently been used as re-
in aqueous methanol at nickel bromide, cyclable electrocatalysts for the reduction
fractal nickel, and Raney nickel electrodes of alkyl halides since low-valent Co species
made of the compressed powders in good are good nucleophiles toward organic sub-
yields [363]. The hydrogenation of acetone strates [367–369]. Examples of such elec-
has been studied in basic aqueous so- trocatalysts are the vitamin B12 derivatives
lutions with a dispersed Raney nickel aquocobalamin (230), dibromo[l-hydr-
electrode [364]. The electrocatalytic hydro- oxy-2,2,3,3,7,7,8,8,12,12,13,13,17,17,18,18-
genation of carvone and limonene at a hexadecamethyl-10,20-diazaoctahydropor-
Raney nickel cathode was investigated phinato]cobalt(III) (231), and cobaloxim
in an aqueous solution containing a (232). The above Co(I) complexes can be
used for the reductive cleavage of the achieved in a DMF-Bu4 NBr-(C) system by
C−X (halogen) bond through the forma- the Co(I)L complex vitamin B12 generated
tion of alkylcobalt(III) complexes, bearing at carbon cloth electrodes, giving (238)
a Co−C covalent bond with a subsequent (Scheme 88) [373].
two-electron reduction to regenerate the A novel Michael-type addition of alkyl
Co(I) species. For example, the β-haloethyl halides to α,β-enones (239) has been
protecting group of the ester (233) can be realized using either aquocobalamin (232)
readily removed by reductive elimination or dibromo[l-hydroxy-8H-HDP]cobalt(III)
of ethylene (235) to liberate the free acid (248) [374]. The electrolysis of (239) in
(234) (Scheme 87) [370–372]. a DMF-LiClO4 /NH4 Br-(Hg) system in-
Intermolecular addition of butyl iodides volves competition between two paths that
(236) to cyclohexenone (237) has been may lead either to bicyclic ketones (240)
C2H5OH/H2O (4:1)/LiClO4/(Hg)
Mediator (231), −1.95 V, 1 °C
R CO2CH2CH2 Br R CO2H + CH2 CH2
−Br−
(233) H (234) (235)
Ph N
O S Me
R=
O N Me
O
Scheme 87 Cathodic elimination for deprotection of a carboxylic acid.
O O
DMF-Bu4NBr-(C)
CH3(CH2)3 I + Vitamin B12s, 81% yield
(CH2)3CH3
(236) (237) (238)
Scheme 88 Cathodic vitamin B12 -catalyzed addition of butyl iodide to cyclohexenone.
O O O
(CH2)n Br (CH2)n − 1Me
DMF/LiClO4/NH4Br/(Hg)
(CH2)n +
−1.9 V, 20 °C
(239)a: n = 3 Mediator (230) or (248)
b: n = 4 (240)a: 2% (241)a: 90%
c: n = 5 b: 95% b: 2%
c: 70% c: 10%
Scheme 89 Cathodic cyclization of bromoalkylenones.
O O
+
X
(242) (243) (244)
Scheme 90 Cathodic addition of ethyl bromide to 2-methyl-1-penten-3-one.

through C−C bond formation, or open- to be useful in the construction of car-

chain products (241) via substitution of bon and hetero-ring systems [376, 377].
bromine by hydrogen (Scheme 89) [374]. A prostaglandin F2 α precursor (247) con-
A device for the Michael-type addition of taining all the structural elements for
ethyl bromide (242) to 2-methyl-1-penten- the C6 to C20 segments with 8R, 9S,
3-one (243), a precursor of the pheromone, 11R, and 12R configurations has been
(dl)-4-methyl-3-heptanone (244), has been electrosynthesized in a one-step operation
made by means of the photocatalytic by sequential two-C−C bond formations.
electroreduction of vitamin B12 in combi- For example, a B12 -catalyzed radical cy-
nation with solar power (Scheme 90) [375]. clization–addition sequence is operative
Radical reactions mediated by organoco- for the binding of chiral cyclopentene
balt complexes (248) have been proven bromoacetal (245) and 1-octyn-3-one (246)
R
hn (vis. light)
Co(III)
X−
Co(II) + R• Further
reactions
e− (−0.8 V (SCE))
R X
Co(I) Co(III): Hydroxocobalamine hydrochloride B 12a
Scheme 91 Generation of carbon-centered free radicals by vitamin B12 -photoelectrocatalysis.
EtO R1
R2
O O
Br DMF-LiClO4/B12
−0.9 V (SCE) > 55% R3
C5H11
R4 (247)
O
(246) OTBDMS
OTBDMS
(245) (247) R1 R2 R3 R4 Yield, %
a OEt H H C5H11CO 26
b H OEt H C5H11CO 21
c OEt H C5H11CO H 8
d H OEt C5H11CO H 13
MeO2C CO2Me +
Me
Me
Me
MeO2C
N N
Me CO2Me
Co ClO4−
H Me
MeO2C N N
(248)
Me
Me [Cob(II)7Cl, ester]ClO4
MeO2C Me CO2Me
Scheme 92 Synthesis of a prostaglandin F2 α-precursor.

(Scheme 92) [378]. A general mode of ac- radical intermediate, which then dispro-
tion for carbon-centered free radicals by portionates to the dialkylated complex
B12 -photoelectrocatalysis is depicted in and the monovalent Co species. The
Scheme 91. dialkylated complex is converted into
Carbon-skeleton rearrangements have the products (250) and (251) through
been catalyzed by heptamethyl-cobyrinate electrooxidation on the anode [384, 385].
perchlorate, [Cob(II)7 Cl, ester]ClO4 , under The cobaloxim-mediated 1,2-acyl migra-
electrolysis conditions [379–383]. Electro- tion of 2-(bromomethyl)cycloalkanones
chemical rearrangements are performed can lead to the formation of ring-enlarged
by the electrolysis of 2-substituted 1- compounds as the major products [386].
bromo-2-ethoxycarbonylpropane (249) in The electrolysis is carried out in an MeOH-
a DMF-Bu4 NBF4 /Co(III) complex-(Pt/Pt) Et4 NOTs-KOH-(Pt) system at a current
system using the Co(III) complex in density of 20 mA cm−2 .
an undivided cell containing imidazole The electroreductive dehalogenation of
(Scheme 93). The trivalent Co complex is α-haloacetic acids has been achieved
electrochemically reduced to the mono- with cobalamin [387]. The hydropho-
valent Co complex, and the resulting bic vitamin B12 Co complex immo-
species reacts with alkyl bromide to give bilized on a glassy carbon electrode
the monoalkylated complex. The subse- (252) may catalyze the electrochemi-
quent one-electron reduction leads to a cal carbon-skeleton rearrangements of
Y
Me Y Y
Y CO2Et
Me Co(III) H3C C Me + H2C CH Me
Br CO2Et CO2Et
CO2Et CO2Et
Me
(249) (250) (251)
Y
Y = CO2Et, COMe, CN 3∼20% yields 53∼85% yields
Scheme 93 Electrochemical rearrangement of 2-substituted 1-bromo-2-ethoxycarbonylpropane.
C C C
C = carbon OH
OH
CO2H LiAlH4
CH2OH
K2Cr2O7, H2SO4
O
OH
Electrode Araldite CT-200
C
OH OH
O O O O N
Co(II)
OH
OH OH n
(252)
Scheme 94 Cathodic dehalogenation with immobilized vitamin B12 .

alkyl halides bearing electron-withdrawing The treatment of the bromoacetal (255)

groups (Scheme 94) [388]. The electrode with catalytic amounts (∼10%) of a
surface is coated with a polymeric Co(I) species, generated by the elec-
monomer, Araldite CT-200, bearing vita- troreduction of cobaloxime (232) in an
min B12 . Vitamin B12 may induce the MeOH-LiClO4 system at −1.8 V, pro-
formation of surfactant aggregates in a duces the cis-fused adduct (256) in
water-in-oil microemulsion offering the 60 ∼ 70% yield (Scheme 96) [392]. Ca-
possibility of selecting a suitable microen- thodic reduction is used for the syn-
vironment for the reactant as a means of thesis of a [Co(CO)3PBu3 ]− complex
controlling kinetics and reactivity [389]. in a methanol-methyl formate medium,
Cobaloxime(I), electrochemically regen- which catalyzes the alkoxycarbonylation
erated from chloro(pyridine)-cobaloxime of dichloromethane to dimethyl mal-
(III) (232), has been employed as a medi- onate in up to 75% yield [393]. The
ator in the reductive cleavage of the C−Br Co(II) complexes are found to be effective
bond of 2-bromoalkyl 2-alkynyl ethers for the homogeneous reduction of gem-
(253), giving (254) through radical trapping dichlorocyclopropanes in the presence of
of the internal olefin (Scheme 95) [390]. An anthracene [394]. The formation of the
interesting feature of the radical cyclization C−C double bond of (258) may be as-
(253)→(254) is the reaction in methanol, cribed to the α-elimination of the Co-H
unlike the trialkyltin hydride-promoted species. Thus, benzalchloride (257) can
radical reactions that need an aprotic non- be converted to a mixture consisting pri-
polar solvent. An improved procedure for marily of cis- and trans-stilbenes (258) by
the electroreductive radical cyclization of the action of electrogenerated Co(I)(salen)
(253) has been attained by the combined (Scheme 97) [395–398].
use of cobaloxime(III) (232) and a zinc A microemulsion made from dodecane,
plate as a sacrificial anode in an undivided water, and didodecyldimethylammonium
cell [391]. The procedure is advantageous bromide has proven to be a good medium
in terms of the turnover of the catalyst and for the catalytic reduction of trans-1,2-
the convenience of the operation. dibromocyclohexane and for SN 2 reactions
R R
Br
MeOH-Et4NOTs/NaOH,-(Pt)
Mediator (232)
O O O O
(253) (254)
R = n-C5H11 70∼80% yields
Ts = 4-CH3C6H4-SO2
Scheme 95 Cyclization of bromoalkyl alkynyl ethers.
Br
Mediator (193)
OEt
60~70% yields
O cis-ring fused O
OEt
(255) (256)
Scheme 96 Cyclization of bromoalkyl alkenyl ethers.

DMF-Bu4NPF6 -(C)
PhCHCl2 PhCH CHPh + PhCH2CH2Ph
Co(II) (salen)
(257) (258) (87%) (259) (5%)
+ (PhCH2)2CHPh + m/e 272

(260) (5%) (3%)
Scheme 97 Stilbene from benzalchloride via an α-elimination at cobalt catalysts.
of alkyl bromides with electrogenerated porphyrin) at −0.49 V (SCE) leads to

Co(I) complexes [399]. the formation of [(TMpyP)Co(I)]3+ . The
The Co(III) complexes with the 1,4,8,11- addition of cyclohexene to this mixture af-
tetraazacyclotetradecane (cyclam) ligand fords cyclohexene oxide. The integration of
are found to behave as redox mediators for the current–time curves for the reduction
the indirect electroreduction of meso-1,2- of [(TMpyP)Co(II)]4+ under a dioxygen at-
dibromo-1,2-diphenylethane (261) lead- mosphere gives a turnover number up to
ing to trans-stilbene (262) in a DMF- 15 during the first 15 min of bulk elec-
Bu4 NClO4 -(Pt) system (Scheme 98) [400]. trolysis. Electropolymerized films of [Co(v-
The use of the Co(I) porphyrin for terpy)2 ]2+ (v-terpy = vinylterpyridinyl) ex-
the homogeneous electroreduction of hibit reactivity patterns, especially with
dioxygen in DMF-Bu4 NClO4 -(C) system regard to ligand exchange, which differ
in the presence of benzoic anhydride from those exhibited by [Co(terpy)2 ]2+
has been developed [401]. The reduc- in solution [402]. The films are active
tion of [(TMpyP)Co(II)]4+ (where TMpyP in the catalytic electroreduction of CO2
= meso-tetrakis(1-methylpyridinium-4-yl) to CO.
2e−
2[Co(II)(cyclam)(Cl)2]0 2[Co(III)(cyclam)(Cl)2]+
Br Br Ph H
In solution + 2Br−
Ph C C Ph
turnover = 2.4 H Ph
H H
(261) (262) 96% yield
Scheme 98 Cathodic elimination at vic-dibromides to stilbenes.
H2O-KNO3 -Ni(II) or Co(III)-(Hg)

NO3− NH2OH or NH3
NH2OH NH3
Catalyst (current yield, %)
Co(III)(cyclam) 88 2
Ni(II)(cyclam) 68 2
Scheme 99 Electrocatalytic reduction of nitrates.

Electrocatalytic reduction of NO3 − takes yields [406]. Catalytic epoxidation of cy-

place efficiently in the presence of a clooctene (263), leading to the epox-
catalytic amount of Co(III)(cyclam) or ide (264), has been performed by us-
Ni(II)(cyclam) in aqueous media at a ing electrogenerated metalloporphyrin oxo
mercury cathode (Scheme 99) [403]. complexes prepared from [5,10,15,20-
A polypyrrole film electrochemically tetrakis-(pentafluorophenyl)porphinato]ir-
deposited on gold electrodes from an on(III)chloride (265) by electroreduction in
MeCN-LiClO4 /Co(OAc)2 solution shows a DMF/Ac2 O-Et4 NClO4 -(Pt/C) system (Sc-
electrocatalytic activity in dioxygen re- heme 100) [407]. The reduced form (266)
duction [404]. The catalytic electroreduc- of the catalyst (265) tends to transfer
tion of dithio dipropionic acid (PSSP) electrons to a dioxygen to generate a su-
with the water-soluble cobalt(III)tetrakis(4- peroxide ion via (267) (Scheme 101). For
trimethyl-ammonium phenyl) porphyrin example, the catalyst (265) reacts with
(CoTMAP) has been studied. The Co acetic anhydride to yield metal oxo por-
phyrin complexes (268) via (269) that are
catalyst adsorbed on the glassy car-
used in epoxidizing cyclooctene (263), lead-
bon electrode plays a major role in
ing to (264) (Scheme 102).
the electroreductive cleavage of the S−S
Carbon dioxide has been reduced
bond [405].
to methanol with the Everitt’s salt
(ES)-mediated electrode in the pres-
15.3.1.3 Iron (Fe) Complex Mediators ence of 1,2-dihydroxybenzene-3,5-disul-
The use of Fe, indium, and zinc as phonato(iron) ferrate(III) complex
sacrificial anodes in the electrochemi- (Scheme 103) [408, 409]. The reduction
cally assisted Reformatsky reaction of proceeds as follows: a weak coordina-
ethyl 2-bromoalkanoates with succinic tion bond is first formed between the
anhydride is found to be effective, giv- central metal of ES and ethanol, then
ing 1-ethyl-3-oxohexanedioates in 49∼80% the subsequent insertion of CO2 onto
DMF/Ac2O-Et4NClO4-(Pt/C), (265)
O
Current efficiency 28.9%
(263) (264)
Scheme 100 Electrocatalytic epoxidation of cyclooctene.
e−
O O−
O2
MIII MII MIII
L L L
(265) (266) (267)
O2−
.
Scheme 101 Reduction of oxygen to superoxide anion.

e− O2− O OAc O
MIII MII MIII MV

Ac2O AcO − AcO −
L L L L
(265) (266) (269) (268)
C C
(270)
O
= Porphyrin dianion, M = Fe or Mn, L = Cl
C C
(264)
Scheme 102 Catalytic cycle for the epoxidation of alkenes with iron or manganese complexes.
(a) CO2 + 6H + + 6ES CH3OH + 6PB + 6K + + H2O
−
(b) PB + K + + e ES
ES = Everitt's salt, K2Fe(II)[Fe(II)(CN) 6 ]
PB = Prussian blue, KFe(III)[Fe(II)(CN) 6 ]
Scheme 103 Catalytic reduction of carbon dioxide to methanol.
the metal complex proceeds to form agent at −1.25 V (SCE) giving 78%
an intermediate Fe(III)-iron-ethyl formate current efficiency for the formation of
complex, which is finally reduced by PhCOCH2 CO2 − [411]. The electroreduc-
ES with the consumption of protons in tion of CO into methanol is also per-
solution to form methanol and the start- formed by using the ES-coated platinum
ing metal complex (Scheme 103a). This electrode as a mediator in the presence
reaction may proceed continuously when of sodium aquapentacyanoferrate(II),
the produced PB is electrochemically re- Na3 [Fe(CN)5 (H2 O)], as homogeneous cat-
duced to ES (Scheme 103b). A large-scale alysts at a three-phase(electrode/solution/
regeneration of ferricyanide from fer- gas) interface (Scheme 104) [412–414].
rocyanide produced in the preparation The mediated electroreduction of CO and
of 3,4,5-trimethoxybenzaldehyde from the CO2 to methanol (see 271→275) has been
hydrazide using a ferri/ferrocyanide re- achieved by the use of surface-confined
dox system has been attained in 70∼75% metal complexes (271), for example,
current efficiency [410]. aquapentacyanoferrate(II), aquopentaflu-
Electrochemical carboxylation of ace- oroferrate(III), and 4,5-dihydroxyben-
tophenone with CO2 coupled with nitrite zene-1,3-disulphonatoferrate(III) (Sche-
reduction proceeds by the controlled- me 105) [346]. The general feature of the
potential electrolysis of CO2 -saturated metal complex capable of operating as a
acetonitrile containing [Fe4 S4 (SPh)4 ]2− , catalyst in the reduction of CO and CO2
NO2 − , PhCOCH3 , and a dehydration is that it should have at least one labile
(a) CO + 4H + + 4ES CH3OH + 4PB + 4K +
(b) PB + K + + e− ES
Scheme 104 Electroreduction of carbon monoxide to methanol.
L L H CO
L M L M OMe
ES + H +
(271) L L (272)
L L PB + K +
L H
MeOH
MeOH L M OC OCH3
(273)
L
L H
PB + K +
ES + H +
ES + H +
PB + K +
L L
L M OMe L M O CH2
(275) L PB + K+ ES + H+ L (274)
L L
Scheme 105 Catalytic cycle for the reduction of carbon monoxide to methanol.
ligand in its coordination shell, which can (Scheme 106) [415]. The reductive fixation
be replaced by a new ligand in the course of CO2 to thioesters catalyzed by
of the reaction. [Mo2 Fe6 S8 (SEt)9 ]3− , leading to α-keto
Electroreductive fixation of CO2 into acid, has also been investigated [416].
formate can be efficiently performed by Similarly, electroreduction of CO2 using
using Fe4 S4 cubane clusters (276) bearing Fe-S clusters (276) is carried out in
a 36-membered methylene backbone a DMF-Bu4 NBF4 /[Fe4 S4 (SCH2 Ph)4 ]2− -
in a DMF-Bu4 NBF4 -(Pt/Hg) system (Pt/Hg) system under CO2 at −2.0 V (SCE)
(CH2)8
N N
X S
S S Fe X
(276)
Fe S
(CH2)8 (CH2)8 a: X = −COCMe2−
Fe S b: X = −COC6H4CH2− (p)
X S Fe
S c: X = −COC6H4− (p)
S X
N N
(The CO part of X is bonded to N)
(CH2)8
Scheme 106 Fe4 S4 cubane cluster for the cathodic fixation of carbon dioxide.
in the presence of benzylthiol (277) to Ligand exchange is completed within

give phenylacetate (278) and a formate 2 min at 20 ◦ C (1 mmol scale). The com-
(Scheme 107) [345]. pound [Fe(C5 Me5 )(dppe)MeCN]+ BF4 −
Methylene addition to the C−C double (284) is isolated in 90% yield.
bond of styrene (281) with [Fe(C5 Me5 )- Reduction of acetylene (286) to ethy-
(dppe) (=CH2 )]+ BF4 − (279) leading to lene (287) is catalyzed by nitrogenase-
phenylcyclopropane (282) proceeds in a like catalysts, [Fe4 S4 (SPh)4 ]3− (289) or
CH2 Cl2 /MeCN-Bu4 NPF6 -Pt system at a [Mo2 Fe6 S9 (SPh)8 ]3− ([Mo-Fe]3− ), which
potential of −0.6 V (SCE) via a radical are electrosynthesized in a CH3 OH/THF-
intermediate (280) (Scheme 108) [417]. LiCl-(Hg) system from [4-Fe]3− (288) or
PhCH2SH
(277)
CO2 PhCH2CO2− + HCO2−
[Fe 4S4(SCH2Ph)4]2−
(278)
Scheme 107 Cathodic reduction of carbon dioxide to formate.
Ph CH CH2
+ e− (281)
Fe CH2 Fe• CH2 Ph
MeCN
(279) (280) (282)
MeCN
+ −e−
[Fe] NCMe Fe• NCMe Me
90% Me
(284) yield (283)
Me
Me Fe+ ; P P = dppe
Fe +•
Me (285)
P
P
Scheme 108 Cathodic cyclopropanation with an iron-methylene complex.
HC CH + 2H + CH2 CH2 (287)

(286)
[ 4–Fe ]2−
(288) e−
1/2 CH2 CH2
(−1.25 V)
[ 4–Fe ]4−
1/2 CH CH + H+
[ 4–Fe ]3− Ph S
Fe S
+ e− (−1.60 V) S Ph 2−
S Fe
[ 4–Fe ]2−
S Fe
(289)
Ph S Fe S S Ph
Scheme 109 Catalytic cycle for the iron-complex-mediated reduction of ethyne to ethene.
[Mo-Fe]3− tetrabutylammonium salts. The by the electroreduction of [Fe(NO)2 Cl]2+

reduced species of (288) or [Mo-Fe]3− are in a propylene carbonate/(Pt/Fe) system
capable of reducing acetylene to ethylene and the catalyst is used in situ for the
(Scheme 109) [418]. cyclodimerization of butadiene (290) to
The water-soluble Fe porphyrin, 3Na+ yield 4-vinylcyclohexene (291) in 98%
[Fe(III)(TPPS)]3−• 12H2 O [H2 TPPS4 − = yield (Scheme 110) [422]. The superiority
tetra-anionic form of meso-tetrakis(π- of inner-sphere catalysts such as the Fe(III)
sulfonatophenyl)porphine], has recently porphyrin complex for the indirect elec-
been shown to be an effective catalyst troreduction of vicinal dibromoalkanes has
for the electroreduction of nitrite to been pointed out in terms of rate constants
ammonia [419]. The Fe meso-tetrakis(N - and selectivity [423].
methyl-4-pyridyl)porphyrin and/or the Hemoglobin, myoglobin, cytochrome
Fe meso-tetrakis(π-sulfophenyl)porphyrin C, and cytochrome oxidase are all
complex shows a catalytic activity electrochemically reduced in the presence
for the reduction of dioxygen in of quinoxaline. Quinoxaline is preferen-
aqueous solutions, leading to hydrogen tially reduced to the anion radical that can
peroxide [420]. release its electron. Metalloproteins can
The reductive behavior of iron-carbene serve as the electron acceptors in which
porphyrins has been investigated. A 2e + the metal ion is reduced [424].
H+ reduction of thiocarbonyl complexes Electrosynthesis of 5-nitroguaiacol from
can lead to the corresponding thioformyl 4-nitroanisole has been performed by the
complexes in a reversible system [421]. electroreduction of Fenton’s reagent in
A preparative method using a ferrous an MeCN/H2 O(1 : 1)-Fe2 (SO4 )2 /HClO4 -
hyponitrite complex, [Fe(NO)2 Cl]2+ , as (Pt/SUS) (SUS = Stainless Steel) sys-
an active electrocatalyst for selective cy- tem [425].
clodimerization has been investigated. The Polymeric Fe phthalocyanine (poly-
active catalyst Fe(NO)2 can be prepared FePc) is known to be a better catalyst
"Fe(NO) 2"
98% yield
(291)
(290)
Scheme 110 Cyclodimerization of butadiene via cathodically prepared Fe(NO)2 .
NH2
N
Poly-FePc
N
Catalyst for oxygen reduction 1-Aminophenazine :
Carbon (292)
cathode
Scheme 111 Cathodic reduction of oxygen at low overvoltage.

Cathode Cu
2e−
2[Fe(III)–TEA] 2[Fe(II)–TEA]
O H
C N
C C
N C
H O
O− H 2e− (293)
C N
C C Dispersed form
N C (293)
−O
H
(294)
O2 On textile
(293)
Scheme 112 Cathodic reduction of indigo to leuco-indigo with iron complexes.
for dioxygen reduction than monomeric mediator, the finely dispersed indigo dye
FePc. The polymeric Fe phthalocyanine- (293) can be reduced under the following
coated electrode is prepared via the ‘‘melt- conditions: the catholyte is prepared by
synthesis’’ method. It shows the lowest mixing Fe2 (SO4 )3 , H2 O, triethanolamine,
polarization and maintains the most pos- and NaOH, and then adding water. In-
itive potential at a 10 mA cm−2 discharge digo is added to the catholyte solution
(Scheme 111) [426]. and a dispersion agent (naphthalenesul-
A glassy carbon electrode coated with fonic acid condensation product), and the
an anodically formed polymer of 1- mixture is electrolyzed at a Cu cathode
aminophenazine (292) mediates the reduc- at −1.05 ∼ −1.10 V (Ag/AgCl). Electrocat-
tion of Fe(III), which occurs in the region alytic reduction of nitrite to ammonia has
of the potential in which the reduction of been demonstrated using a water-soluble
(292) takes place [427]. ion porphyrin as the catalyst [430].
The reduction of indigo (293), which is
insoluble in water and alkaline solutions,
to the disodium salt of leuco-indigo 15.3.2
(294), which is soluble in alkaline so- Indirect Reduction with Mediators
lutions, is crucial to the application of Containing Palladium, Rhodium, Iridium,
(293) as a textile dye. Recently, a pro- and Platinum
cedure for indirect electroreduction of a
dispersed (293) dye with coordination com- 15.3.2.1 Palladium (Pd) Complex
pounds of Fe(II) and Fe(III) salts, and Mediators
triethanolamine has been developed as a A catalytic electrode for the reduction
mediatory system (Scheme 112) [428, 429]. of aqueous bicarbonate (CO3 H− ) lead-
With this reversible redox system as a ing to a formate (HCO2 − ) has been
X DMF/Et4NCN/Et4NCl CN
Pd[PPh3]4,–0.3 ~ –0.8V
F3C Turnover (162) F3C
(295) (296)
Scheme 113 Cathodic cyanation of aryl chlorides.
devised. A Pd-impregnated polymer on active state. In the case of electrocya-

a metallic electrode is shown to cat- nation, (295) is converted to (296); the
alyze the reaction of hydrogen with number of turnovers of Pd-complex cata-
CO3 H− to form HCO2 − [431]. A Pd(II)- lysts can be improved from 8 to 162 by
metalloporphyrin complex has been used the passage of a small amount of elec-
as a novel homogeneous catalyst for tricity. In addition, Ni(0)L4 complexes can
the electroreduction of CO2 leading be used in place of Pd(0)L4 complexes as
to an oxalate (see Table 17) [352]. The electrocatalysts for the cyanation of acyl
Pd(triphos)L(BF4 ) complexes (L = MeCN, chlorides.
P(OMe)3 , PEt3 , P(CH2 OH)3 , and PPh3 ) The Pd(0)-catalyzed displacement of
are able to catalyze the electroreduction allylic acetates (297) with various nu-
of CO2 to CO in acidic acetonitrile so- cleophiles via the allylic Pd(II) com-
lutions [432]. The analogous Ni and Pt plex (298) is a well-established procedure
complexes do not catalyze the CO2 reduc- (Scheme 114). Through attack of electrons
tion under similar conditions. (+2e− ) in place of nucleophiles, (298) is
Long-lived homogeneous Pd(0)L4 [L = expected to undergo a reductive cleav-
P(Ph)3 ] catalysts for the cyanation of aryl age providing allylic carbanions (299) and
chlorides (295) (X = Cl) have been de- the acetate anion along with Pd(0) com-
veloped, which are activated by cathodic plexes. The latter can then be captured by
reduction (Scheme 113) [433]. A high tem- various electrophiles (polarity inversion,
perature, 130 ◦ C, and a high-boiling sol- Scheme 114) leading to (300) [434]. This
vent, dimethylformamide, are required procedure is useful for the deprotection
because Pd does not insert into the aryl of allyl esters under neutral conditions.
C−Cl bond at lower temperatures. Cat- Recently, a mechanistic study of the Pd-
alytically inactive metal species formed in catalyzed reaction of allylic acetate (297),
undesirable side reactions with cyanide are using carbonyl compounds as an elec-
electrochemically restored to a catalytically trophile, has been reported [435].
R
2e− R
R OAc _ + AcO−
PdL
AcO (299)
(297) (298)
E+
Pd(0)L R E
(300)
Scheme 114 Pd(0)-catalyzed nucleophilic substitution of allylic acetates.

(a) RH + X− M + + e− R− M + + 1/2 H2
R3 R3
R1 R1
R− M +
(b) C CH CH OAc C CH CH R
Pd(0)-complex
R2 (301) R2 (302)
RH : Active hydrogen compound
X− M + : Supporting salt
Scheme 115 Pd(0)-catalyzed substitution of allylic acetates with electrogenerated carbanions.
The Pd(0)-catalyzed electrophilic reac- derivatives in 60∼99% yield [438]. Electro-

tion of allyl acetates (301) with elec- catalytic dechlorination of chloroaromatics
trochemically induced carbanions lead- on a palladium-loaded carbon felt cathode
ing to (302) has been performed in an aqueous medium has been attained
(Scheme 115) [436]. The electrolysis is car- in good yields [439].
ried out in a DMF-Et4 NClO4 -(Pt) system in The Pd(0)-catalyzed electroreductive cou-
the presence of the active hydrogen com- pling of aryl halides (303) is a currently
pound, Ph3 P, and Pd(II)(PhCN)2 Cl2 at a relevant topic. In the electroreduction
current density of 0.26 A dm−2 and the of aryl halides (307) the replacement of
allyl acetate (301). the halogen atom by hydrogen predomi-
The Pd-catalyzed electro-cleavage of nantly takes place giving (306). Difficulties
the C−O bond of allyl aryl ether pro- are encountered, however, when aryl–aryl
ceeds smoothly in a DMF-Bu4 NBF4 -(Mg)- coupling products (305) via (304) are
(Stainless Steel) system, giving depro- wanted (Scheme 116). An efficient elec-
tected products in 73∼99% yield [437]. troreductive coupling of aryl bromides
The sp–sp intermolecular coupling re- (307) (X = Br) and iodides (307) (X = I)
action with the Pd water-soluble catalyst into biaryls (310) has been shown to occur
prepared in situ from Pd(II) acetate and sul- in a DMF/Et4 NOTs/(Pb cathode) system
fonated triphenylphosphine in an MeCN- in the presence of Pd(0) and/or Pd(II) cat-
H2 O system yields diynes in 45∼65% alysts (Scheme 117) [440].
yields [438]. Similarly, the sp2 –sp coupling The cross-coupling between two differ-
of 2-iodophenols or 2-iodoanilines and ent aryl iodides (311) and (313), leading to
terminal alkynes followed by intramolec- (314), can be achieved by using stoichio-
ular cyclization gives indol and furan metric amounts of Pd(0) complexes in the
PdX e−
X
R R R
R L
(303) (304) (305)
L P(C6H5)3 Pd(0)L
H (306)
R
Scheme 116 Cathodic coupling of aryl halides.

Ar PdX
Ar X e−
(307)
(308)
Pd(0) Ar PdX
X−
e−
Ar Ar Ar Pd Ar Ar X
(310) (309) (307)

X−
Scheme 117 Catalytic cycle for cathodic coupling of aryl halides.
I t-Bu (313) Bu-t

I–Pd
Pd (0)
2e−
Me2N Me2N (314)

Me2N
(311) (312)
Scheme 118 Cross coupling of aryl iodides.
electrolysis media (Scheme 118) [440]. On has been shown to occur in an aprotic
the basis of kinetic results, the transient solvent saturated with CO2 in the pres-
species is thought to be an anionic penta- ence of electrocatalysts such as PdCl2 L2
coordinated bisarylpalladium(II) complex, or PdL4 [L = P(Ph)3 ]. For example, the
which undergoes rapid loss of the halide electrolysis of 4-t-butyliodobenzene (315)
ligand to yield a neutral bisarylpalla- (R = t-Bu; X = I) in a DMF-Et4 NOTs-
dium(II) species [441–446]. (Pt/Pb) system in the presence of a catalytic
Electroreductive carboxylation of aryl amount of Pd(II)Cl2 [P(Ph)3 ]2 and triph-
halides, β-bromostyrene, and allyl acetates enylphosphine gives 4-t-butylbenzoic acid
X (318) CO2H
R R
(315)
−• CO2, H +
e− e−
PdX PdX
R R
(316) (317) −X −
Pd(0)
Scheme 119 Catalytic cycle for carboxylation of aryl iodides.

(321)
R
R 2e−, H+ R
Ar X [Ar Pd X] Ar Ar
−X−
(319) (320) (322) Pd X (323)
Pd(0)
2e−
Pd(II)
Scheme 120 Cross coupling of aryl halides and alkynes or alkenes.
(318) (R = t-Bu, 81%) and t-butylbenzene of CO2 on Pt metals has been stud-
(5%) (Scheme 119) [447]. Similarly, the ied [451]. Chemisorbed particles are found
Pd(II) complex catalyzes the electrosyn- to have formed only on Pt and Rh. The
thesis of aromatic carboxylic acids under electroreduction of CO2 on these metals
CO2 atmosphere [448]. The electrocar- proceeds as a result of the interaction of
boxylation of vinyl triflates is performed CO2 molecules, activated in the course
with CO2 and a catalytic amount of of adsorption on the metal surface, with
PdCl2 (PPh3 )2 to give α,β-unsaturated car- chemisorbed hydrogen. However, the fur-
boxylic acids [449]. ther reduction of these chemisorbed in-
Electroreductive hydrocoupling of aryl termediates proceeds very slowly because
halides (319) with olefins (321) and of their very strong adsorption. Neither
acetylenes (321) also proceeds with reductive chemisorption of CO2 nor inter-
PdCl2 [P(Ph)3 ]2 as the electrocata- actions of CO2 with adsorbed hydrogen
lyst in a DMF-Et4 NOTs-(Pt/Pb) sys- have been observed with Ir, Pd, Os or
tem. Electrochemical cross-coupling of Ru [452].
4-t-butyliodobenzene (319) (Ar = 4-t- A poly-π-nitrostyrene coated Pt
BuC6 H4 , X = I) with styrene affords electrode has been used for the
the corresponding coupling product (323) electrocatalytic reduction of 1,2-dibromo-
(Ar = 4-t-BuC6 H4 , R = Ph) in 85% yield 1,2-diphenylethane to stilbene in a
(Scheme 120) [450]. A polymer-supported CH3 CN–R4 NBF4 system. The turnover
1,2-bis(diisopropylphosphino)benzene Pd- number for catalyst sites is estimated to
(II) complex is found to show a bet- be 10 000 [453].
ter catalytic activity than the structurally
analogous monomeric Pd(II) complex in 15.3.2.3 Rhodium and Iridium Complex
the Heck arylation of methyl acrylate by Mediators
iodobenzene [451]. Recently, Rh(dppe)2 Cl (dppe = 1,2-bis(di-
phenylphosphino)ethane) has been shown
15.3.2.2 Platinum (Pt) Complex Mediators to catalyze the electroreduction of CO2 in
The adsorption of CO2 on Pt electrodes an acetonitrile solution. The Rh complex
has been intensively studied and the can be electrochemically reduced to the
chemisorbed particles are known to be corresponding rhodium hydride.
tightly bound to the surface and not to The electroreduction of [Rh(dppe)2 ]+
be desorbed by rinsing. Recently, the (324) and analogous Ir complexes leads
mechanism for the reductive adsorption to a neutral species HRh(0)(dppe)2
(a) [Rh(dppe) ]+ +
2 2e− RhH(dppe)2
(324) (325)
(b) Metal(dppe)2+ + e Metal(0)(dppe)2

(326) (327)
(c) Rh(0)(dppe)2 + CH3CN RhH(dppe)2 + •CH2CN
(328) (329)
Scheme 121 Reduction of rhodium(I) and reaction of rhodium(0) species.
(324)
Rh(dppe)2(CO2)
− CH3CN
e CO2
(330)
Rh(0)(dppe)2 Rh(dppe)2+(OCHO)− + •CH2CN
(328) (331) e−
CH3CN
CO2
(329) –CH2CN
dppe: 1,2-Bis(diphenylphosphino)ethane
Scheme 122 Reduction of carbon dioxide by electrogenerated rhodium(0).
(325) (Scheme 121a) in the initial pathways (Scheme 122) [454, 455]. The
step. The neutral species Rh(0)(dppe)2 current efficiencies for the formation of
(328) may occasionally react with the formate anion vary between 42%
acetonitrile to afford RhH (dppe)2 and 22%, depending on the electrolysis
(329) (a slow reaction) (Scheme 121c). periods. The electrocatalytic reduction of
Electrogenerated (328) may react with CO2 to either CO or the formate ion,
CO2 to generate the ionic metalloformate in an MeCN-Bu4 NPF6 -(Pt) system using
Rh(dppe)2 + (OCHO)− (331) via two [cis-M(bpy)2 (O3 SCF3 )]2+ (M = Rh −1.5 V;
e−
S-H
[Rh(dppe)2]+ [Rh(0)(dppe)2] RhH(dppe)2
90%
(332) (333) yield (325)
−Cl−
•
Cl
(335) (334)
Scheme 123 Reduction of cyclohexyl chloride to cyclohexyl radicals by rhodium(0).

Ir −1.59 V vs. SCE), has been reported species useful for regio- and enantioselec-
[338]. tive olefin hydroformylation [458].
Constant-potential electrolysis of the Electrocatalytic hydrogenation of car-
[Rh(dppe)2 ]Cl in an MeCN-Bu4 NClO4 - bonyl groups has been carried out by elec-
(Hg) system gives RhH(dppe)2 (325) in trolysis of the ketone (336) in an aqueous
ca. 90% yield. When cyclohexyl chloride EtOH-LiClO4 -(C) system in the presence of
(334) is added to the [Rh(dppe)2 ]+ (332) Rh complexes to yield the alcohol (337) in
electrolysis solution, the radical interme- 95 ∼ 99% yields (Scheme 124) [459, 460].
diate (335) together with Cl− is produced Electroreduction of CO2 catalyzed by a
as shown in Scheme (123) [456]. The cy- rhodium complex, [(RhCp*)3 (µ3 -S)2 ]2+ in
clohexyl radical (335) generated in this an MeCN-Bu4 NBF4 -(C) system produces
manner has several channels for product formate and oxalate in 60% current effi-
formation. ciency [461]. The direct electroreduction of
The Rh(III)(bpy)3 Cl3 complex catalyzes NAD+ at −1.1 V (SCE) leads to inactive
the electroreduction of CO2 to a formate dimers and even at −1.8 V, active NADH
in an H2 O-Et4 NClO4 -(C/Pt) system (See is formed in only 50% yield. Recently, the
Table 17) [347]. use of the [Rh(bpy)2 ]+ complex (338) as
Recently, it was found that the asym- an efficient electron-transfer agent for the
metric hydroformylation of styrene by regeneration of NADH from NAD+ has
Rh4 (CO)12 L2 via electroreduction in the been reported [462]. The electroreduction
presence of CO and hydrogen provides of NAD+ to NADH using the agent (338)
regio- and enantioselective products (e.g. produced cathodically from [Rh(bpy)3 ]3+
>30%) when chiral ligands, (L = (1R, 2S)- proceeds well in the tris-HCl Buffer-(Pt/C)
Ph2 PNMeCHMeCHPhOPPh2 and Me2 C- system (Scheme 125). The regenerated
(NMePPh2 )-CH2 OPPh2 ), are used [457]. NADH is oxidized by ketone (339) giv-
Electroreduction of Rh and Pt complexes ing alcohol (340) under catalysis of horse
can be applied to the synthesis of active liver alcohol-dehydrogenase (HLAD). A
aq. EtOH-LiClO4-(C) OH
O
−1.2 V (SCE), 95~99% yields
H
(336) (337)
Scheme 124 Electrocatalytic hydrogenation of carbonyl compounds.
[Rh(bpy)3]3+
2e−
[Rh(bpy)2]3+ NADH R CO R′
(339)
HLADH
[Rh(bpy)2] + NAD + R CH R′
(338)
Cathode bpy H+ OH
(340)
Scheme 125 NADH-regeneration in an electroenzymatic reduction.

HCO2− Rh(III)(C5Me5)(bpy)2+ NAD(P)H

(341)
CO2 H Rh(III)(C5Me5)(bpy) + NAD(P) +

(342)
Scheme 126 Electrocatalytic NAD(P)H regeneration with formate as a hydride donor.
more efficient, purely homogeneous re- The electroreduction of CO2 in an aqueous

duction system, (341)→(342) : NAD+ → DMF(9 : 1)-[Ru(bpy)2 (CO)2 ]2+ (346) or
NADH in which the reducing equiva- [Ru(bpy)2 (CO)Cl])-(Hg) system at −1.50 V
lents (two electrons and a proton) are (SCE) at pH 6 produces CO and
supplied by the formate is shown in molecular hydrogen (H2 ) [348, 468].
Scheme (126) [463]. A similar electrolysis at pH 9.5 af-
fords not only CO and H2 but
15.3.3 also the formate anion, HCO2 − [349].
Indirect Reduction with Mediators The [Ru(bpy)2 (CO)2 ]2+ (346) is elec-
Containing Ruthenium and Osmium
troreduced by two electrons to afford
15.3.3.1 Ruthenium (Ru) Complex [Ru(bpy)2 (CO)] (343) with CO elimination.
Mediators The compound (343) reacts with CO2 to
The catalytic reduction of CO2 with Ru give the complex [Ru(bpy)2 (CO)(CO2 − )]+
complexes under electroreduction con- (344), which is protonated to afford
ditions has been documented [464–467]. [Ru(bpy)2 (CO){C(O)OH}]+ (345) and
H2O
CO 2+
2e − CO +
(bpy)2Ru 2e −
CO (bpy) 2Ru
CO
H+ (346) Cl
OH −
−
Cl
H+,2e − HCO2−,H +
CO
+ CO 0
(bpy) 2Ru
(bpy)2Ru
C O
OH− (343)
(345) OH
CO2
H2O CO
+
(bpy) 2Ru
H+ C O
(344)
O−
Scheme 127 Catalytic cycle for the electroreduction of carbon dioxide to carbon monoxide
and formate.
MeCN-Bu4NPF6 -Ru(II)-(C)
(a) CO
100% yield
CO2
MeCN-Bu4NPF6 -Ru(III)-(C)
(b) HCO2H
64% yield
Scheme 128 Electroreduction of carbon dioxide to carbon monoxide and formate.
[Ru(bpy)2 (CO)2 ]2+ . The former is re- with the Rh(III) complex yields a mix-
duced to provide HCO2 − (Scheme 127). ture of formate and molecular hydro-
Product-selective electroreduction of CO2 gen in 64% (12% current efficiency)
to either CO or formate in an (Scheme 128b). Electroreduction of CO2
MeCN-Bu4 NPF6 -(Pt) system has been using a [Ru(bpy)2 (CO)2 ]2+ (346) catalyst
shown to occur using precursor com- in an MeCN-Bu4 NClO4 -(Hg) system in
plexes such as [Ru(trpy)(dppe)Cl]+ the presence of Me2 NH and Me2 NHHCl
or [cis-Rh(bpy)2 (TFMS)2 ]+ (trpy = 2,2 2 - affords a formate and DMF with current
tripyridine; TFMS = trifluoromethane- efficiencies 75.7% and 21.4% [351].
sulfonyl anion) [338]. The Ru(II) complex Recently, C−C bond formation has been
is found to be a good CO2 reduction found to a certain extent in the elec-
catalyst at a potential of −1.4 V (SCE) troreduction of CO2 catalyzed by a Ru
and the electrolysis results in the ex- complex [Ru(bpy)(trpy)(CO)](PF6 )2 [469].
clusive formation of CO (Scheme 128a). Further investigations reveal that the se-
In contrast, the electroreduction of CO2 lective formation of HCO2 − and C2 O4 2−
Co[II]TPP O2
Ru[NH3]63+ + H2O
e− (347)
(352)
Ru[NH3]62+
Co[III]TPP[O2 − ]
Cathode (353)
Co[III]TPPO2H (348)
(349)
(351) Ru[NH3]63+ Ru[NH3]62+ + H +

(350)
e− Cathode
CoTPP: Cobalt tetraphenylporphyrin
Scheme 129 Catalytic cycle of ruthenium(III) reduction with (Co(II)TPP) immobilized in Nafion.
has been attained in the electroreduction coating [472]. The electrons are transferred
of CO2 catalyzed by mono- and di- from the electrode to the almost immobile
nuclear Ru complexes that are prepared catalyst sites by (350) ions incorporated
by the reaction of [Ru(bpy)2 Cl2 ] with in the coating. Scheme (129) provides a
dmbbbpy (2,2 -bis(1-methylbenzimidazol- schematic depiction of the catalytic cycles
2-yl)-4,4 -bipyridine) [470]. The electrore- (350)→(351) and (347)→(348)→(349),
ductive conversion of CO2 into methanol which proceed within the Nafion
has been performed using a Ru-modified coatings on the electrodes [472]. The
glassy carbon electrode prepared by [CoP(pyRu(NH3 )5 )4 ]8+ complex prepared
electropolymerization of mercaptohydro- from the reaction of Ru(NH3 )5 OH2 2+
quinone [471]. Ru-modified electrodes pos- (355) with [CoP(pyH)4 ]4+ [cobalt meso-
sess excellent functions in the selec- tetrakis(4-pyridyl)porphyrin] (357) within
tive reduction of CO2 to methanol Nafion coatings on graphite electrodes acts
with almost 100% current efficiency as a catalyst in the four-electron reduction
in the potential range −0.6 to −0.8 V
of the dioxygen (Scheme 130) [473]. A
(SCE). Electrodes composed of RuO2 +
Ru-cofacial diporphyrin is effective as a
TiO2 (35/65 mol%) and RuO2 + Co3 O4 +
dinitrogen electroreduction catalyst [474].
SnO2 + TiO2 (20/10/8/62 mol%) show
high current efficiencies for methanol pro-
duction from CO2 [350]. Some results are 15.3.3.2 Osmium (Os) Complex Mediators
presented in Table 17. Recent work on the use of polypyridyl-
Cobalt tetraphenylporphyrin (Co(II) aquo [Os(VI)(trpy)(O)2 (OH)]+ complexes
TPP) (347) is immobilized in Nafion works (358) has shown that the reduction may
for the electroreduction of a dioxygen when proceed stepwise through a series of
[Ru(NH3 )6 ]2+ (350) ions are present in the oxidation states [(358)→(359)→(361)] with
−
(a) Ru(NH3)6 + e Ru(NH3)62+
3+
(354) (355)
5+
(b) 355 + CoP(pyH)4 CoP(pyH) 44+ + (354)
(356) (357)
Scheme 130 Reduction of [CoP(pyH)4 ]4+ with ruthenium(II) in the oxygen reduction.
e−
[Os(VI)(trpy)(O)2(OH)] + Os(V)(trpy)(O)2(OH)
−e−
(358) (359)
(a) E1/2 = 0.10 V
2e−,2e + e−
(359) Os(III)(trpy)(OH)3 [Os(II)(trpy)(OH)3] −
−2e−,−2H + (360) −e− (361)
(b) E1/2 = −0.22 V E1/2 = −0.67 V
Scheme 131 Reversible three-electron redox couple of Os(VI)/Os(III).

the retention of a common coordination use of surface-confined metal complexes

number. A reversible three-electron redox like a diaquobis(oxalato)chromate(III) and
couple based on Os(VI)/Os(III) has been aquopentachlorochromate(III) as media-
reported [475]. Because of the differences tors [346]. The general feature of metal
in the pH dependence of the couples complexes, capable of operating as cata-
involved, Os(V) (359) becomes a stable lysts in the reduction of both CO2 and CO,
oxidation state from pH = 11 to pH = is the requirement of at least one labile lig-
13.3. The redox couples are shown in and in their coordination shell, which can
Scheme (131). be replaced by a new ligand in the course
A suitable comparison of the Os(VI)/ of the reaction.
Os(III) couple is the well-studied three- Recently, the reductive C–C cou-
electron oxidant HCrO4 − , where the in- pling of benzyl and allyl halides, for
termediate oxidation states Cr(V)/Cr(IV) example, (362)→(363), has been de-
appear to be unstable with respect to dis- veloped by electrochemically regener-
proportionation. However, the Os system ating Cr(II) complexes. The electrore-
shows a dramatically enhanced electro- duction of Cr(III) to Cr(II) complexes
chemical reversibility compared to Cr(IV). takes place in a DMF-(Pt/C) system
This feature may play an important role at −0.4 V (SCE) (Scheme 132) [477]. 2-
in the ability of related systems that act as Arylpyrimidines and 2-arylpyrazines are
redox catalysts. electrosynthesized in 61∼79% yields in
Recently, effective chiral ligands for a DMF/Py-NiBr2 (bpy)-(Fe/Ni)-system by
the enantioselective dihydroxylation of the reaction of 2-chloropyrimidine and/or
olefins have been intensively investi- 2-chloropyrazine with aryl halides [478].
gated. Among the reported asymmetric Electrochemical alkenylation of aldehydes
dihydroxylation systems, the superior- using an Al sacrificial anode in the pres-
ity of an H2 O/t-BuOH-K3 Fe(CN)6 /K2 CO3 ence of Cr(II)/Ni(II) catalysts affords the
system with chiral ligands, that is, corresponding allyl-alcohol derivatives in
dihydroquinidine (DHQD) and/or a di-
good yield [479]. Electrochemical arylation
hydroquinine (DHQ) derivative, has been
of aromatic aldehydes with aryl halides
mentioned (see Sect. 15.2.4.7) [476].
using a stainless steel sacrificial anode cat-
alyst, in the presence of NiBr2 (bpy), leads
15.3.4
to the corresponding arylated secondary
Indirect Reduction with Mediators
alcohols in good yield [480]. The major ad-
Containing Chromium, Molybdenum, and
vantages of the procedure are: (1) the use
Tungsten
of a catalytic amount of Cr complexes;
15.3.4.1 Chromium (Cr) Complex (2) facile product isolation by extraction
Mediators with cyclohexane; and (3) operation as a
Chromium(II) salts are widely used in continuous process.
organic synthesis. However, the high sen- Pinacol formation from ketones and
sitivity to air and the low solubility of aldehydes by cathodic reduction has been
Cr(III) salts in anhydrous solvents pre- enhanced in the presence of Cr(II) com-
vent their synthetic use as electrocatalysts. plexes. Electrolysis of a mixture of ben-
The electroreduction of both CO2 and CO zophenone (364) and chromium chloride
to methanol has been achieved by the hexahydrate in a DMF-NaClO4 system
DMF- CrCl2 -(Pd/C), −0.7 V

Br
Cr(II) Cr(III) (363)

(362)
−
e 77% yield
Scheme 132 Cathodic coupling of cyclohexenyl bromide with chromium(III) as mediator.
Ph
DMF-NaClO4 -(Hg) H
(a) Ph OH
O 80% yield
(365)
Ph Ph
OH
(364) DMF-NaClO4 -CrCl3•6H2O Ph
(b) Ph
70% yield Ph Ph
(366) OH
Scheme 133 Cathodic coupling of benzophenone (pinacolization) with chromium(III) as mediator.
at −0.65 V in a divided cell under ni- The one-electron reduction of carbe-

trogen gives the pinacol (366) (70%) nium ions to the corresponding radicals
(Scheme 133) [481–483]. An important re- has been performed using Cr(II) com-
quirement for obtaining good yields of the plexes as electrocatalysts. Hexamethyl-
pinacol is the presence of a catholyte that tropylium cations can be electrochemi-
is preelectrolyzed at ca. −0.6 V (Ag/Ag+ ) cally reduced in a CH2 Cl2 -Bu4 NClO4 -(Pt)
for ca. 0.3 F mol−1 , prior to the addition of system to give a mixture of hexameth-
carbonyl compounds. Under these condi- ylcycloheptatriene (ca. 40%) and its dimer
tions, β-ionone, β-ionylideneacetaldehyde, (ca. 20%) [486]. Alkylation of methyl phe-
and retinal can lead to the corresponding nylacetate occurs by electrolysis of a
pinacols in 75%, 60%, and 25% yields, re- η6 -tricarbonylchromium complex in an
spectively [483]. Absence of the Cr complex MeCN-Et4 NBr-(Mg)-(Pt) system in the
causes the formation of the benzhydrol presence of alkyl bromide [487]. A free-
(365) (Scheme 133). radical cyclization of α-bromoacetals to
The electroreductive coupling of the 2-alkoxy-tetrahydrofurans induced by the
hindered aromatic ketones (367) has activated Cr(II) acetate has been re-
been achieved in a DMF-Bu4 NBr-(Hg) ported. The electrolysis is carried out in
system by the aid of CrCl3 or MnCl2 a DMF-LiClO4 /Cr2 (OAc)4 (H2 O)2 -(C) sys-
as the electrocatalyst (Scheme 134) [484, tem in the presence of ethylenediamine,
485]. The reductive coupling proceeds at and the acetal is added to this solu-
a less negative potential [E1/2 − 1.44 ∼ tion [488].
−1.53 V (SCE)] than the reduction of the Secondary trichloromethyl carbinols and
ketone (−1.63 ∼ −2.01 V). In some cases, their corresponding esters can be reduced
Mn electrocatalysts favor the reduction with the electrogenerated Cr(II)Cl2
to the carbinol (369), whereas a Cr complex to form dichlorovinylidene
catalyst promotes the formation of the compounds via a 1,2-elimination in
pinacol (368). one step. In-cell electroreduction of
HO OH
O R2
R1
R2 R2
DMF-Bu4NBr-(Hg) R1 +
R2
R1 OH R1
Mn(0) Mn(II)
or or (368) (369)
(367) DPTA
Cr(II) Cr(III)
e− Yield, %
(368) (369)
a) b) a) b)
Tetralone 84 (85) --- ---
Indanone 66 (63) --- ---
Chromanone 74 (78)
Benzophenone 0 (74) --- ---
Xanthone 0 ( 0) 78 (18)
0 (90)
a) with Mn complex b) with Cr complex
Scheme 134 Cathodic coupling of arylketones with chromium(III) as mediator.
3-trichloromethyloxetan-2-one (370) in DPTA (373)) at pH = 6. The Cr(II)L

an aqueous H2 SO4 (5%)/CrCl2 -(Pt/Pb) complexes are strong reducing agents
system affords dichlorovinylacetic acid for triple bonds as well as the nitro
(371) in good yield (Scheme 135) [489]. group [490].
After extraction of the product (371)
with dichloromethane, the catholyte 15.3.4.2 Molybdenum (Mo) Complex
can be used again for the next Mediators
electrolysis. Recyclable Cr(III)/Cr(II) redox Dinitrogen-coordinated complexes of Ti,
couples have been used as reduction Zr, Mo, and W have been studied as potent
catalysts in different electrolytes [490]. The mediators in electrolysis media [491–495].
electroreductive preparation of Cr(II)Cy- Preliminary results from the electroreduc-
DTA and Cr(II)DPTA complexes is carried tion of [Mo(N2 RR )(S2 C-NMe2 )3 ]+ reveal
out in an aqueous AcONa-electrolyte in the that the two-electron reduction of the
presence of Cr(III)L (L = CyDTA (372), cation leads to electroactivation of the
O
O Cl
H2O-H2SO4(5%)-(Pt/Pb)
CH CCl3 CrCl2, −0.7~ –1.0 V (Ag/AgCl) C CHCH2CO2H
Cl
(371)
(370) good yield
N (CH2CO2−)2
N (CH2CO2−)2
(372) N CH2CO2− (373)
N (CH2CO2−)2 CyDTA DPTA
N (CH2CO2−)2
Scheme 135 Reductive elimination with chromium(III).

[Mo(N2)(dppe)]
(374) RX
H2N NR2
R
[Mo (N (dppe)2X] +
[ Mo(N2)(H2NNR2)(dppe)2 ]
R
(378) − (375)
2e − 2H
+ 2e − –X
R
[Mo(N2)(N2R2)(dppe)2] [Mo (N (dppe)2]
R
(377) −N2 (376)
N2
dppe: R2 2
2PCH2CH2PR 2 (R2 = alkyl or aryl); R = aryl; X = Br, I
Scheme 136 Catalytic cycle for the cathodic conversion of dinitrogen into 1,1-dialkylhydrazine.
N2 RR ligand towards attack by elec- cycle (374)→(375)→(376)→(377)→(378)

trophiles and that the subsequent reduc- to produce organohydrazines, H2 N-NR2 ,
tion/protonation are shown to liberate the from dinitrogen (Scheme 136) [495]. Con-
free hydrazine in good yield [494]. stant current electrolysis of [Mo(NNR2 )
Combining the electroreduction of (dppe)2 X]+ (375) under nitrogen in a
the hydrazido Mo complex (377) THF-Bu4 NBF4 -(Pt or Hg) system at
and the regeneration of the dini- −1.8 V (SCE) leads to the rapid forma-
trogen Mo complex (374) opens up tion of [Mo(0)(NNR2 )(dppe)2 ] (376) after
the possibility of an electrochemical the capture of two electrons. Further
2e −
[P[Mo(V)]4[Mo(VI)]8O40]7− [P[Mo(V)]6[Mo(VI)]6O40]9−
(379) −2e − (380)
fast
Relatively slow
Cl − + 3H2O ClO3− + 6H +
Scheme 137 Cycle for the molybdenum-catalyzed reduction of chlorate to chloride.
TsOH/H2O
trans-[W(N2)2] trans-[W(IV)(dppe)(NNH2)TsO] +
−N2
(381) (382)
THF-Bu4NBF4 -(Hg)
−2.6 V (Fc +/Fc)
NH3
Scheme 138 Reduction of a tungsten-hydrazine complex to ammonia.

NC CN
H
N H
N+
NC
THF-Bu4NBF4-(Hg)
− + −
P P 4e ,2H ,−F H2N N
W N
P P H
(383) (384)
F
NC H NC
H+
C N N
N H N N
H H
NH H (385)
H (386)
Scheme 139 Reduction of a 1-hydrazino-2,2-dicyanoethylene-tungsten complex to a

5-amino-4-cyanopyrazole.
reduction takes place at a much slower the revived parent dinitrogen complex
rate and at the end of the electrolysis (381) [497]. Electrolysis on a Pt cathode
up to 45% of [Mo(N2 )2 (dppe)2 ] (374) and gives substantially lower yields of trans-
60%∼70% of hydrazine are isolated. The [W(N2 )2 ] (381). Electroreductive cleav-
results suggest a successful electrochem- age of the W−N bond of the [WNH-
ical cycle for nitrogen-atom fixation as CH=C(CN)2 (dppe)F]+ complex (383) has
shown in Scheme (136) [495]. Electrore- been shown to give 5-amino-4-cyanopy-
ductively produced 12-molybdophosphate razole (384) in yields of up to 50%
(379) behaves as a reducing agent for via the processes (383)→(385)→(386)
chlorate ions leading to chloride ions →(384), which are beneficial to the
(Scheme 137) [496]. recovery of [W(N2 )2 (dppe)2 ] complexes
(Scheme 139) [498, 499].
Recently, the C−C bond formation
15.3.4.3 Tungsten (W) Complex Mediators through an electroreduction of a diazo-
Electrosynthesis of ammonia has been alkane group, incorporated as a lig-
achieved using a W(dppe)2 complex. and into W complexes, has been re-
Controlled potential electrolysis of transported. One-electron reduction of trans-
[W(NNH2 )• (dppe)2 TsO]+ (382) (Scheme [W(N2 CH2 )L2 F]+ in an MeCN-Bu4 NBF4 -
138) in a THF-Bu4 BF4 -(Hg) system gen- (Hg) system affords W(N2 CH2 CH2 N2 )
erates free NH3 and N2 H4 along with L4 F2 (L = dppe) in 55% yield [500].
R1 THF-WCl6-(Pt/Al) R1 R2
O
−1.85~ −1.97 V (SCE) R1
R2 R2
(387) (388)
R1 = Me, Ph
R2 = H, Me, Ph, 46~96% yield
Scheme 140 Tungsten-catalyzed reductive dimerization of carbonyl compounds to alkenes.

Electrochemically reduced W species sulfoxides to the corresponding sulfones

tend to transform carbonyl compounds in high efficiency [504].
into olefins after dimerization. For exam-
ple, benzaldehyde (387) can be quantita-
tively converted into stilbene (388) by elec- 15.3.5
troreduction in a THF-Bu4 NClO4 /WCl6 - Indirect Reduction with Mediators
(Al/Pt) system at a potential of −1.9 V Containing Manganese and Rhenium
(SCE) (Scheme 140) [501].
The electrogeneration of alkene meta- 15.3.5.1 Manganese (Mn) Complex
thesis catalysts from WCl6 has been stud- Mediators
ied intensively. The reduction of WCl6 The combination of the cathode
in CH2 Cl2 (or ClCH2 CH2 Cl)-Bu4 NPF6 - with a catalyst for the electroreduc-
(Al/Pt) under a controlled potential of tion of dioxygen has attracted great
−1.2 V (SCE) gives the in situ active interest. In particular, metal por-
catalyst species (389). A metal-carbene- phyrins and phthalocyanines are pro-
initiated process similar to that for olefin posed as potential catalysts [505]. Re-
metathesis with conventional catalysts has cently, the catalytic electroreduction
been proposed. 2-Pentene (390) can be of dioxygen using [5,10,15,20-tetrakis-(1-
converted to 3-hexene (391→392→393) methylpyridinium-4-yl)porphinato]man-
and 2-butene (394→395→396) via alkene ganese has been performed in H2 O-
metathesis in a CH2 Cl2 -WCl6 /Al/e− sys- KH2 PO4 /NaOH(pH = 7)-(C) [506]. It is
tem (Scheme 141). In place of WCl6 , widely recognized that the porphyrin in
MoCl5 salts can be used in the same a high-spin divalent state plays the role
manner [502, 503]. The electroreduction of an active species. The electrochem-
of dioxygen to hydrogen peroxide, which ically activated dioxygen enables olefin
oxidizes tungstate to pertungstate in the epoxidation through electroreduction. The
solution, brings about the oxidation of catalytic reaction sequence is of particular
CH2Cl2 -(Pt/Al)
WCl6 [CH2 = WCl4] (389)
e−
2-pentene (390)
(391) W + W
(394)
(392) W = CHEt W = CHMe

(395)
(393) W
W
(396)
3-hexene 2-butene
Scheme 141 Electrogenerated metathesis catalyst and reaction with 2-pentene.

interest since it involves the essen- containing benzoic acid as a proton

tial elements of the cytochrome P-450 source, [Mn(TPP)Cl] as a catalyst, 1-
catalytic cycle. The electrolytic epoxida- methylimidazole as the axial base, and
tion proceeds in a CH2 Cl2 -Bu4 NClO4 - the olefin as a substrate. The electroreduc-
(C) system containing an axial base tion of an [Mn(III)(salen)]+ [salen = N ,N -
(1-methylimidazole), olefin, and benzoic ethylenebis(salicylaldiminato)]) complex
anhydride in the presence of Mn(III) (397) in an MeCN-Et4 NClO4 (AcO)2 O/O2 -
tetraphenylporphyrin chloride [507]. Very (C) system in the presence of 1-
recently, electrochemical olefin epoxida- methylimidazole and olefin (398) yields
tion with a Mn meso-tetraphenylporphyrin the corresponding epoxide (399) in over
(TPP) catalyst has been carried out with 48% yield, based on the electrochemical
hydrogen peroxide generated at polymer- charge passed, together with allylic oxi-
coated electrodes [508]. The glassy carbon dation products (400) (Scheme 142) [509].
electrode is coated with a film of poly- Electrocatalytic epoxidation of cyclohex-
[Ru(bpy)3 ]2+ , having high permeability ene by a Mn(III) porphyrin complex
to dioxygen and very low permeability using an electron mediator in the pres-
to porphyrin. The polymer film prevents ence of methylene blue has been re-
electroreduction of the high-valent metal ported [510]. Hindered aromatic ketones
oxo porphyrin [Mn(=O)TPP]. Hydrogen (401) can be converted electrochemically
peroxide is electrogenerated by reduc- to either the corresponding pinacols (402)
tion of dioxygen in methylene chloride or to benzylic alcohols (403) using a
O
MeCN-Et4NClO4
+ Mn(V) O + OH
O2 + e, (397)
(398) (399) (400)
O O > 48% yield
Mn
(397) C N N C
H H
Scheme 142 Cathodic epoxidation with Mn(III)-complex and oxygen.
O HO OH
R2
R1
R2 DMF-Bu4NBr-(Hg) R2
R1 +
R2
R1 OH R1 (403)
Mn(0) Mn(II)
(401) (404) (402)
e− R 1 = R2
66~84% yield
a (CH2)2
b (CH2)3
c O(CH2)2
Scheme 143 Manganese-mediated pinacolization and hydrogenation of aryl ketones.

Mn(II)/Mn(0) (404) couple as a mediator industrial catalytic reduction of CO. In this

(see Scheme 143) [485]. connection, the electrochemical conver-
sion of formylrhenium to hydridorhenium
15.3.5.2 Rhenium (Re) Complex Mediators complexes has been investigated. The
Current interest in formylrhenium com- electroreduction of cis-[(CO)5 ReRe(CHO)-
plexes stems from their potential in the (CO)4 ]− in an MeCN-Et4 NClO4 system by
fac-Re(bpy)(CO)3Cl (405)
−e − e−
[Re(bpy)(CO)3Cl] –• (406)
−Cl − e−,−Cl −
CO + CO32− Re(bpy)(CO)3 CO2 CO + [AO]− [Re(bpy)(CO) 3] − CO2

(407) (409)
CO2 + 2e− Re(bpy)(CO)3CO2 A + e− [Re(bpy)(CO) 3CO2] −
(408) A = an oxide ion acceptor (410)
Scheme 144 Catalytic cycle of cathodic carbon dioxide reduction with rhenium complexes to
carbon monoxide.
[pH 1.0]
2e−, 3H +
[Re(V)(py)4(O2)]+ [Re(III)(py) 4(OH)(OH2)]2+
–2e−, –3H +
(411) (412)
E1/2 = −0.42 V e−, H +
[Re(II)(py)4(OH2)2]2+
−e−, −H +
(a) −0.75 V (413)
[pH 7.0]
2e−, H +
(411) [Re(III)(py) 4(O)(OH)] (414)
−2e−, −H +
−0.90 V e−, 2H +
[Re(II)(py) 4(OH)(OH2)] +
−e−, −2H +
(b) −1.28 V (415)
[pH 13.0]
2e−, H + e−
(411) (414) [Re(II)(py) 4(O)(OH)] −
−2e−, −H + −e−
(c) −1.12 V −1.39 V (416)
Scheme 145 pH-dependent redox couples of rhenium(V)-complexes.

the passage of 0.035 F mol−1 of electricity ligands in these three oxidation states.
(turnover ca. 30) quantitatively yields cis- Reduction potentials and dominant pro-
[(CO)5 ReRe(H)(CO)4 ]− [511]. The cyclic ton compositions are given for pH =
voltammetry of fac-Re(bpy)(CO)3 Cl (405) 1.0 (411→412→413) (Scheme 145a), 7.0
in the reduction of CO2 to CO in (411→414→415) (Scheme 145b), and 13.0
an MeCN-Bu4 NPF6 -(Pt) system is in- (411→414→416) (Scheme 145c). Reduc-
dicative of two different electrocatalytic tion at potentials more negative than that
pathways as follows: (406)→(407)→(408); of the Re(III/II) couple gives the Re(II)
(406)→(409)→(410) (Scheme 144) [354]. complex, which is a good electrocatalyst
The electrolysis of [fac-Re(bpy)(CO)3 ]2 in for the reduction of water to hydrogen
CO2 -saturated DMF-Bu4 NPF6 at −1.8 V over the pH range of 0.5∼13.
results in the production of CO with
current efficiencies over 85%. The com-
15.3.6
plex Re(vbpy)(CO)3 Cl (vbpy = 4-vinyl-4 -
methyl-2,2 -bipyridine) coated with a poly-
Containing Titanium, Tin, and Lead
meric film on a Pt electrode, electro-
chemically reduces CO2 to CO [353]. The
turnover numbers attained using the 15.3.6.1 Titanium (Ti) Complex Mediators
modified electrode greatly exceed those Titanium ions can also be used as re-
observed for the analogous electrocat- dox catalysts for the indirect cathodic
alytic reduction of CO2 by Re(bpy)(CO)3 Cl reduction of nitro compounds (417).
in a homogeneous solution (bpy = 2,2 - The electroreduction is carried out in
bipyridine) (See Table 17). The trans- an H2 O-H2 SO4 /Ti(SO4 )2 -(Pb/Cu) system
[Re(V)(py)4 (O)2 ]+3 complex is known to at 45∼80 ◦ C under 5∼20 A m−2 . Ni-
be in a stable oxidation state and reduction trobenzene, dinitrobenzene, nitrotoluene,
leads to strong reducing aqua complexes 2,4-dinitrotoluene, 2-nitro-m-xylene, nitro-
with a potential use as electrocatalytic phenol, 2,4-dinitrophenol, nitrophenetole,
reductants [512]. The electroreduction is o-nitroanisole, 4-nitrochlorotoluene, ni-
carried out in an H2 O-CF3 SO3 H-(C) sys- trobenzenesulfonic acid, and 4,4 -dinitro-
tem in the presence of the Re(V) complex, stilbene-2,2 -disulfonic acid can all be
and the potentials for the Re(V/III) and reduced by this procedure to the cor-
Re(III/II) redox couples are pH-dependent responding amino compounds (418) in
due to the acidic character of the aqua good yields (Scheme 146) [513–516]. Tin
NO2 NH2
H2O-H2SO4 /Ti(SO4)2 -(Pb/C)
79~90%
Y
M(0) M(II) Y
(417) 2e−
(418)
Cathode
Electrolysis conditions: C 6H6/HCl/SnCl2/(C)

C6H6/HCl/ZnCl2/(C)
Scheme 146 Titanium(III)-mediated reduction of substituted nitrobenzenes.

and zinc powders formed in an acidic p-nitroaniline [524] can also be reduced at
aqueous solution by electrolysis at high a Ti/TiO2 electrode. An excess of electrons
current density (0.5 A cm−2 ) can be used will accumulate on TiO2 particles, which
for the reduction of nitro compounds may improve the rate of dioxygen reduc-
to the corresponding amines [517–521]. tion [525]. An electrochemically generated
The conversion and current yields can low-valent Ti complex acts as a reducing
exceed 90%. Pilot-scale productions of agent for the conversion of 1-nitroalkenes
aniline and p-aminophenol have been rea- to the corresponding nitriles [526]. During
lized [514]. the electroreduction of the nitroalkene, the
The catalytic reduction of o-nitrophenol yellow color of the Ti(IV) chloride-DMF
by the surface of a Ti(IV)/Ti(III) re- complex changes to deep violet.
dox system on a Ti/TiO2 electrode has Electrochemical amination of enoic
been used in a preparative-scale opera- acids has been performed using an electro-
tion [522]. 5-Nitro-salicylic acid [523] and generated Ti3+ species as a homogeneous
Ti4+ + e− Ti3+
(a)
•
Ti3+ + NH2OH Ti4+ + NH2 + OH−
(b) (419) (420)
• H+
Ti3+ + NH2 Ti4+ + NH3
(c)
CH CO2H H2N CH CO2H

•
+ NH2 •
CH CO2H CH CO2H
(d) (421) (420) (422)
H2N CH CO2H Ti3+, H+ H2N CH CO2H

+ Ti4+
•
CH CO2H CH2 CO2H
(e) (422) (423)
Scheme 147 Reductive amination of maleic acid.
• HO CH CH CO2H
Ti4+ [NH2]
HO (424)
e− −OH−
HO CH2 CH CO2H
Ti3+ NH2OH
HO NH2
(425)
Cathode
Scheme 148 Synthesis of d,l-dopa by a reductive amination.

catalyst. The amination of maleic acid 15.3.6.2 Tin (Sn) Complex Mediators
(421) with (419) gives aspartic acid (423) Recently, the electrochemical recycling
via radicals (420) and (422) in high yield of allyltin reagents has been realized
(Scheme 147) [527]. dl-Dopa (425) is elec- for the first time in protic solvents.
trosynthesized by the amination of (424) Difficulties in the recycling of metal-
in an aqueous H2 SO4 -Ti4+ -(Hg) system lic allyl reagents in situ are due to the
in the presence of hydroxylamine sulfate fact that reaction conditions that allow
(Scheme 148) [528]. (l) generation of the organotin reagents;
It is known that the Ti complex acts as (2) allylation of carbonyl compounds; and
a reversible carrier of electrons from the (3) reductive regeneration of zero or low-
cathode to the catalytically active Mo(III) valent metal complexes, in a single cell
complex in a Ti-Mo-pyrocatechol system at the same time, have to be found.
for the electroreduction of CO on a The Grignard-type allylation of carbonyl
mercury cathode [529]. compounds has been performed in an
O OH
1 2 R1
R R
MeOH R2
(426) (427)
Br2Sn 2 MeO(Br)2Sn
(428) (430)
Br
(429) [Sn(II) or Sn(0)]
Cathode
Scheme 149 Tin-mediated reductive allylation of carbonyl compounds.
Br (429) (434)
Pb(0) [Br] +
2e−
PbBr
(431)
2e−
Pb(II) Br −
Anode
Cathode R CHO
OH Br
(432)
R Br
(433)
Scheme 150 Barbier-type allylation of carbonyl compounds with electrogenerated lead(0).

MeOH/AcOH-(Allyl)2 SnBr2 -(Pt) system The dimethylpyrrolidinium-Sn medi-

at 50∼55 ◦ C. As illustrated in Scheme 149 ated reduction of aryl bromides, bear-
[530], diallyltin dibromide (428) produced ing electron-withdrawing and electron-
from metallic Sn and allyl bromide in donating groups to give the corresponding
methanol reacts with carbonyl compounds debrominated products, has been de-
(426) to give the allylated products (427) to- scribed [531].
gether with allyldibromotin monomethox-
ide (430). The latter compound (430) may
be reduced at the cathode to di- or zero- 15.3.6.3 Lead (Pb) Complex Mediators
valent Sn, which reacts smoothly with Barbier-type allylation (429→433) of car-
allyl bromide to regenerate diallyltin di- bonyl compounds with allyl bromide
bromide (428). (429) has been achieved through recycling
Bn
HN
R
Hydrolysis
(436)
Anode Cathode
mBr − M(n)
M′Brm− Bn
+ n e−
N
MBr Br −
M′(0) (437)
R
−m e− (431) (M = Pb)
M′Brm M(0)
Bn
N Br
M′ = Al, Zn M = Pb, Bi, etc.
(435) R Bn = benzyl
(429)
Scheme 151 Barbier-type allylation of imines with electrogenerated lead(0).
Anode Bn (439) Cathode

CF3• , CO2 HN
Pb(II)
R 2
−e− e−
H +
Bn
N
CF3CO2 − Pb(0)
R (438)
Bn
(440)
CF3CO2H N
(435)
R
Scheme 152 Lead(0) catalyzed cathodic hydrodimerization of imines.

R1 R1
H
N S H2O/CH2Cl2 -HClO4-(Pb) HN S
H H 77~100% yields H H
N Y N Y
O R1 = PhCH2, PhOCH2 O
CO2R2 R2 = Me, PhCH2 CO2R2
(441) (442)
Y = H, Cl
Scheme 153 Cathodic hydrogenation of a thiazoline ring.
of the in situ generated allyllead com- additives results in the formation of a

plex (431) in a DMF/AcOH-PbBr2 -(Pt) complex mixture. Probably, the imine
system in the presence of cyclohex- (435) associates with TFA to afford the
ene (434) as a bromine-trapping agent iminium ion (438) that undergoes a
(Scheme 150) [532]. one-electron reduction with cathodically
An electroreductive Barbier-type allyla- generated Pb(0) to form the 1,2-diamine
tion of imines (434) with allyl bromide (439) (Scheme 152). Electroreductive hy-
(429) also occurs in a THF-PbBr2 /Bu4 NBr- drogenation of the C=N double bond
(Al/Pt) system to give homoallyl amine of thiazoline-azetidinone derivatives (441)
(436) (Scheme 151) [533]. The combina- has been performed in an H2 O/CH2 Cl2 -
tion of Pb(II)/Pb(0) redox and a sacrificial HClO4 -(Pb) system to afford (442) in
metal anode in the electrolysis system 77∼100% yield (Scheme 153) [535]. A Pb
plays a role as a mediator for both cathodic cathode, together with the change of the
and anodic electron-transfer processes. electrode polarity using a commutator, is
The metals used in the anode must have essential for the conversion.
a less positive anodic dissolution poten-
tial than the oxidation potentials of the 15.3.7
organic materials in order to be present or Indirect Reduction with Mediators
to be formed in situ. In addition, the metal Containing Zinc (Zn), Mercury (Hg), and
ion plays the role of a Lewis acid to form Cadmium (Cd)
the iminium ion (437) by associating with
imine (435) (Scheme 151). The use of Zn powder in a multiphase sys-
Electroreductive hydrodimerization tem is a way to solve many of the difficulties
(435→439) of the imine (435) has been involved in the operation of electroorganic
performed in a THF-CF3 CO2 H(TFA)/ processes under a low maximum cur-
PbBr2 -(Pt) system using an undivided rent density [513–516]. A three-phase sys-
cell (Scheme 152) [534]. For the conver- tem, water/organic, substrate/metal pow-
sion, both TFA and PbBr2 are indis- der can be used for the reduction of
pensable, since the lack of either of the halides and nitro compounds under a high
aq. HCl(0.1 M)/ZnCl 2(4 M)-(C/Al)

Ph NO2 Ph NH2
Current efficiency 90%
(443) Organic efficiency 98% (444)
Scheme 154 Zinc-mediated reduction of nitroaryl compounds to amines.

current density (>0.5 A cm−2 ). Electrore- the substrate dissolved in a second

ductive dechlorination of polychlorinated phase to give aniline (444) in 98% yield
biphenyls has been performed using zinc (Scheme 154) [515]. Zinc and tin are the
phthalocyanine as a mediator in an H2 O- best metals for the high current-density
HClO4 -(C) suspension system, leading to reduction in which chemical and current
biphenyl in quantitative yield [536]. yields can exceed 90% [516].
The preparative electroreduction of ni- Electrochemical activation of the Zn
trobenzene (443) is performed in an species has been attained in a DMF-
aqueous HCl/ZnCl2 -(C/Al) system with Et4 NClO4 -(Zn/Pt) system [537, 538]. The
R1
R1
2e−, Zn anode, DMF
C O + Cl
NiBr2(bpy), 5% yield
R2 C
R2
(a) (445) (446) (447) OZnCl
NiBi2(bpy) + bpy + 2e− Ni(0)(bpy)2

(b) (448)
Cl
Ni(0)(bpy)2 + (446) Ni + bpy
bpy
(c) (448) (449)
1/2 NiCl2(bpy) 2 + 1/2 Ni

DMF (450)
(d) (449)
R1
Zn2+,
Ni(bpy) + R2 C
(e) (445) (451)
OZnCl
Scheme 155 Nickel-zinc-mediated cathodic allylation of carbonyl compounds.
O
(H2C)n Br-CMe2CO2Et HO2C (CH2)n
O DMF/Bu4NBr-(Zn/Ni) CO2Et
H2O, H +, 50~75% yields O
O
(453): n = 1; b: n = 2
(a) (452): n = 1; b: n = 2
Me Me
Zn + Br C CO2Et BrZn C CO2Et
Me Me
(b) (454) (455)
Scheme 156 Nickel-zinc-mediated cathodic Reformatsky reaction with anhydrides.

reactivity of ultrafine Zn powders, proof ethyl 2-bromoalkanoates with succinic

duced by the use of ultrasound, has been anhydride (452) (n = 1) has been per-
evaluated for the Reformatsky reaction, formed successfully in the absence of
Barbier allylation, alkyne reduction, re- any Ni(II) species (Scheme 156a). The
ductive dehalogenation, and so on [539]. electrolysis of the anhydrides (452) and the
The combination of a sacrificial Zn an- bromide is carried out in a DMF-Bu4 NBr-
ode and an NiBr2 (bpy) complex realizes an (Zn/Ni) system in an undivided cell to give
efficient electrosynthesis of homoallylic al- 3-oxoalkanedioates (453) [541]. Anodically
cohols (447) from allylic chlorides (446) generated Zn cations probably react with
(or acetates) and carbonyl compounds the anions derived from the electroreduc-
(445) (Scheme 155) [302]. The electrore- tion of the bromide (454) to form the Re-
ductive allylation of the carbonyl com- formatsky reagent BrZnCMe2 CO2 Et (455)
pounds (445) using a Ni catalyst together (Scheme 156b).
with the Zn(II) species is carried out in a The mechanism of the Zn chloride-
DMF-Bu4 NBr/NiBr2 -(Zn/C) system. The
assisted, palladium-catalyzed reaction of
Ni bipyridine complex is readily reduced
allyl acetate (456) with carbonyl com-
at −1.2 V (SCE) (Scheme 155b). The zero-
pounds (457) has been proposed [434].
valent Ni species, which reacts very rapidly
The reaction involves electroreduction of a
with an allylic chloride (k > 200 M−1 s−1 ),
Pd(II) complex to a Pd(0) complex, oxida-
may afford the (π-allyl)nickel chloride
tive addition of the allyl acetate to the Pd(0)
(449) (Scheme 155c). However, dispropor-
complex, and Zn(II)/Pd(II) transmetalla-
tionation of the Ni complex is observed in
DMF in contrast to acetonitrile as shown in tion leading to an allylzinc reagent, which
Scheme 155d. The zinc anode may provide would react with (457) to give homoallyl al-
the Zn(II) species that avoid side reactions cohols (458) and (459) (Scheme 157). Sub-
involving the carbonyl compounds and stituted β-lactones are electrosynthesized
minimize the reduction of allylic chlorides. by the Reformatsky reaction of ketones and
The mechanism of the ZnBr2 -assisted, ethyl α-bromobutyrate, using a sacrificial
nickel-catalyzed Reformatsky reaction has Zn anode in 35∼92% yield [542]. The effect
been discussed [540]. The reaction involves of cathode materials involving Zn, C, Pt,
the electroreduction of a Ni(II) complex Ni, and so on, has been investigated for the
to a Ni(0) complex, oxidative addition of electrochemical allylation of acetone [543].
the α-chloroester to the Ni(0) complex, Electroreduction of CO2 on a Zn elec-
and Zn(II)/Ni(II) transmetallation, lead- trode is performed in an aqueous K2 SO4 -
ing to an organozinc Reformatsky reagent. (Pt/Zn) system. Faradaic efficiency for the
Most recently, the Reformatsky reaction formation of CO (80%), formate (10%),
R1
C O OH OH
R
R2 (457) DMF-Et4NOTs/ZnCl 2
+ R C R1 + C R1
Pd(II)
R OAc
R2 R2
(456) (458) (459)
Scheme 157 Palladium-zinc-mediated cathodic addition of allyl acetate to carbonyl compounds.

OMe OMe
H2O-Bu4NOH-(SUS/Hg)
80% yield
(460) (461)
Bu4N • (Hg)n
H+
Bu4N + + nHg
OMe −• OMe
+
_
H
Bu4N • (Hg)n Bu4N + + nHg

(462) (463)
Scheme 158 Mercury-catalyzed Birch reduction of anisole.
and dihydrogen (10%) has been attained at halides catalyzed by NiBr2 (bpy) complexes
the potential of −1.6 V (Ag/AgCl) [544]. in a DMF-ZnBr2 -(Zn) system [547].
The reaction of 2-bromomethyl-1,4- The Birch-type electrochemical reduc-
dibromo-2-butene with aldehydes or ke- tion (460)→(461) has been shown to
tones in the presence of the electrogen- proceed through the action of tetra-
erated reactive zinc in DMF at 0 ◦ C gives butylammonium amalgam in the steps
the corresponding isoprenylated alcohols (460)→(462)→(463), in contrast to a di-
in good yields [545]. The electroreduction rect electron transfer from the electrode
of a catalytic amount of ZnBr2 in an MeCN- to the aromatics (Scheme 158) [548]. The
ZnBr2 -(Zn) system, which provides active preparative-scale reduction of anisole, of
zinc, catalyzes the reductive coupling of 1,2,3,4-tetrahydro-6-methoxynaphthalene,
allyl bromides and chlorides with car- and several aromatic steroids is performed
bonyl compounds with high regioselectiv- in an H2 O-Bu4 NOH-(Hg) system. The
ity [546]. 2-Arylpyridines (40∼60% yields) unique aspect of the reduction is the
are prepared by electroreductive coupling proposed formation of a tetrabutylammo-
of 2-halopyridines and aryl or heteroaryl nium amalgam complex, Bu4 N(Hg)n (465)
Hg,e−
Bu4N+ Bu4N • (Hg)n
(464) (465)
Scheme 159 Generation of tetrabutylammonium amalgam.
O O
Me Me
aq. MeOH-H2SO4-(Hg)
91% yield
Cl
(466) (467)
Scheme 160 Cathodic removal of a vinylic chlorine atom.

(Scheme 159) [549, 550]. Temperature and the desired product (467) in 91% yield.
electrolyte concentration are found to have The Hg cathode plays the role of a re-
a profound effect on the reaction rate. The ducing catalyst. Electrochemical reduction
Bu4 N(Hg)n can be used for the reduction of 8-bromobornan-2-one in an HMPA-
of β-estradiol 3-methyl ether and the reac- Bu4 NBr-(Pt/Hg) system also suggests the
tion has been shown to be more selective formation of an organomercurial inter-
than the conversion methods based on mediate that leads to the formation of
alkali metal-ammonia reduction [551]. dihydrocarvone as the major product [553].
Electroreductive removal of the chlorine Indirect electroreduction of allyl alcohols
atom from 2-methyl-3-chlorocyclopenten- leading to the corresponding unsaturated
1-one (466) has been performed in an aque- hydrocarbons is attained using a mer-
ous MeOH-H2 SO4 -(Hg) system at −0.80 cury electrode in a strongly acidic medium
to −0.85 V (SCE) (Scheme 160) [552]. In containing an iodide salt [554]. The reac-
the course of the reaction, an Hg com- tion involves transformation of the alcohol
pound is produced in a dimeric form, into the iodide, the reaction of the io-
which undergoes further reduction to yield dide with mercury, the protonation of the
Ph Br DMF-LIClO4 -(Hg) Ph
Ph +
Br 2e−, −Br − Br
(469) (470)
(468)
51% yield 41% yield
Scheme 161 Cyclopropane formation by cathodic γ -elimination of a 1,3-dibromide.
O O
2e−, (indirect)
(PhSe)2, 72% yield
O O
O OH
(471) (472)
Scheme 162 β-Hydroxyketones by reductive ring opening of α,β-epoxyketones with
diphenydiselenide.
CO2Me CO2Me
OH
O 2e−, (indirect)
(PhSe)2, 72% yield
O O
(473) (474)
Scheme 163 β-Hydroxyketosteroid by reductive ring opening of α,β-epoxyketosteroid with
diphenydiselenide.
organomercury compound, and the reduc- allylation occurs using either a Pt cathode
tion of the Hg salt to hydrocarbon and Hg. along with a Cd anode or a Pt cathode and
Benzyl alcohols are similarly reduced to a Cd-modified Pt anode [563].
the corresponding hydrocarbons.
The electroreductive preparation of
15.3.8
highly strained small-ring compounds
is a useful general synthetic method Containing Selenides (Se) or Tellurides (Te)
[555–557]. The electroreduction of 1,3-
dibromide (468), leading to the cy-
clopropane derivative (469) has been Electroreductively generated PhSeSePh
achieved via an organo Hg species, which and PhTeTePh anions work as media-
involves sequential one-electron reduc- tors for the ring-opening of α,β-epoxy
tions with the intervention of organo carbonyl compounds (471) and (473) lead-
Hg(I) radicals and dimeric Hg(I) species ing to the corresponding β-hydroxy com-
(Scheme 161) [558–560]. pounds (472) and (474) (Schemes 162 and
Removal of the iodine atom from aryl 163) [564]. For example, the electrolysis of
iodides proceeds smoothly in a DMF- (473) in an MeOH-NaClO4 -(Pt) system in
Bu4 NClO4 -(Hg) system [561, 562]. A Cd- the presence of PhSeSePh and dimethyl
modified electrode-assisted allylation of malonate affords the ring-opening prod-
aldehydes and ketones has been attained uct (474) in 72% yield (Scheme 163). The
in a DMF-Et4 NClO4 system, in which the direct electroreduction of epoxy ketones
R1 R1 R1
CO2Me 2e− CO2Me CO2Me
R2 R2 + R2
O (PhSe)2 or (PhTe) 2
OH OH
SePh
(475) (476) (477)
Scheme 164 β-Hydroxyesters by reductive ring opening of α,β-epoxyesters with diphenydiselenide.
R1 R1 R1
CN 2e− CN
R2 R2 + R2 CN
O (PhSe)2 or (PhTe) 2 OH R3 OH
R3 Y R3
(478) (479) Y = PhSe, (480)
PhTe
Scheme 165 β-Hydroxynitriles by reductive ring opening of α,β-epoxynitriles with diphenydiselenide.
OSO2Me
2e−, (PhSe)2
R CO2Me R CO2Me
DMF-NaClO4 -(Pt/C)
(481) (482)
Scheme 166 Desoxygenation of α-hydroxyesters via reduction of the methanesulfonates with
diphenyldiselenide as mediator.
provides the β-hydroxy ketones (ca. 30% (476) in 68% yield, while at 50 ◦ C (477)
yield) together with dehydration and pina- is formed in 75% yield (Scheme 164).
colization products [565, 566]. The novel Interestingly, the use of PhTeTePh at room
mediator-associated ring-opening reac- temperature affords (477) directly. The
tions of epoxy compounds can be used PhSe− or PhTe− assisted electroreduction
for the preparation of β-hydroxy ke- of α,β-epoxy nitrile (478) at room
tones, β-hydroxy esters, and nitriles temperature produces α-(phenylseleno)-
from their corresponding α,β-epoxy com- or α-(phenyltelluro)-β-hydroxy nitriles
pounds. The ring-opening is carried out in (479) (Y = Te) (Scheme 165). The direct
a THF/H2 O(9/1)-Bu4 NBF4 -(C) or DMF- conversion of (478) to (480) can be achieved
Et4 NOTs-(C) system in the presence of via electrolysis at 50 ◦ C.
dimethyl malonate as a proton source. The methanesulfonates (481) of α-
The electroreductive ring-opening of hydroxy esters can be converted to the
α,β-epoxy esters (475) and nitriles deoxygenated esters (482) in 70∼88%
(478) proceeds stepwise as shown in yields by indirect electrolysis with Ph-
Schemes (164 and 165). In both cases, SeSePh as a recyclable reagent in a divided
the intermediates (476) and (479) can cell (Scheme 166). The procedure involves
be isolated when the mediator-assisted the formation of α-phenylselenoester by
reductions are carried out at room substitution of the α-methylsulfonyloxyl
temperature. The whole reduction can group with the PhSe− followed by dis-
be completed at 50 ◦ C. For example, placement of the α-phenylseleno group
the electrolysis of a phenylglycidic ester with PhSe− . The electrolysis is performed
(475) (R1 = Ph, R2 = H) in an MeOH- in a DMF-NaClO4 -(Pt/C) system in the
NaClO4 -(Pt) system in the presence of presence of PhSeSePh and ethyl malonate
PhSeSePh at room temperature gives at 50 ◦ C [567].
R1 R1
R1
DMF-SmCl3 -(Mg/Ni)
2 C O R2 C C R2
80%~90% yields
R2 OH OH
(483) (484)
Scheme 167 Samarium-mediated cathodic hydrodimerization of carbonyl compounds.
O Me
Cl +
Me O − Mg2+ Cl −
Sm2+ Sm3+
(485) (486)
e−
Cathode
Anode: Mg Mg2+ + 2e−
Scheme 168 Samarium-mediated Barbier-type reaction of carbonyl compounds with allyl halides.
15.3.9 anodes (Mg or Al) in an undivided

Indirect Reduction with Mediators cell [568].
Containing Miscellaneous Metal The Barbier-type reaction of aldehydes
Complexes and ketones with allyl halides (485) in the
presence of SmI2 , leading to homoallyl
alcohols (486), has received recent interest
15.3.9.1 Samarium (Sm) and Indium (In)
as a one-step alternative to the Grignard
Complex Mediators
The potential of lanthanide compounds reaction. However, the reactions require
as reagents in organic synthesis has at- the use of stoichiometric amounts of the
tracted much attention from electroor- reducing Sm(III) species. Recently, the
ganic chemists. In particular, low-valent electroreductive Barbier-type allylation of
lanthanides are used as reagents for vari- carbonyl compounds in an SmI2 -mediated
ous coupling reactions of carbonyl com- reaction has been developed [569]. The
pounds and/or organic halides. Sm(II) electrolysis of (485) is carried out in
derivatives play the role of one-electron a DMF-SmCl3 -(Mg/Ni) system in an
transfer agents in the C−C bond forming undivided cell to give the adduct (486)
reaction. The first use of the active Sm(II) in 50∼85% yields (Scheme 168) [569].
species as mediator in an electrolysis is Electrosynthesis of γ -butyrolactones has
attained by the coupling of carbonyl com- been achieved by the reductive coupling
pounds (483) leading to the corresponding of ethyl 3-chloropropionate with carbonyl
1,2-diols (484) (Scheme 167) [568]. The compounds in the presence of a catalytic
electrolysis is carried out in DMF or N - amount of SmCl3 [570].
methyl 2-pyrrolidone in the presence of The Sm-catalyzed synthesis of α-dike-
5∼10% of SmCl3 by the use of sacrificial tones from aromatic esters [571], the
DMF-Bu4NBr/SmCl3-(Mg/Ni)
2 Ar CO2R Ar CO CO Ar
50%~90% yields
(487) (488)
Scheme 169 Samarium-catalyzed synthesis of diketones from aromatic esters.
DMF-Bu4NBF4/SmCl3(10%)
Br CO2Me CO2Me
100% yield
(a) (489) (490)
Ph CH CH Br Ph CH CH2
90% yield
(b) (491) (492)
Scheme 170 Samarium-catalyzed cathodic debromination of aryl bromides.
DMF-Bu4NBr/SmCl3 -(Mg/Ni)
Ph O CH2CH CH2 Ph OH
90% yield
(493) (494)
Scheme 171 Samarium-catalyzed cleavage of allyl phenyl ethers.

reductive cleavage of C−X bonds [572], an SmCl3 catalyst can be attained in

and the deprotection of the allyl moiety a DMF- Bu4 NBF4 /SmCl3 (10%)-(Mg/Ni)
from alkyl and aryl allyl ethers [573] system, giving (490) and (492) in good
have all been performed effectively. The yields (Scheme 170). The use of the elec-
electrochemically supported Reformatsky trogenerated Sm species is also effective in
reaction of ketones with β-lactones has the electroreduction of aromatic chlorides
been performed by the use of In complexes and fluorides [572].
to yield β-hydroxy esters in 80% yield [574]. The SmCl3 -catalyzed electroreductive
The Sm-assisted reductive dimeriza- cleavage of allyl ethers (493) leading to
tion of aromatic esters (487), leading (494) has been performed in a DMF-
to diketones (488) is carried out in Bu4 NBr-(Mg/Ni) system in the presence
a DMF-Bu4 NBr-(Mg/Ni) system in the of SmCl3 (10 mol%) in an undivided
presence of SmCl3 as a mediatory catalyst cell (Scheme 171) [573]. A similar ether
(Scheme 169) [571]. cleavage does not proceed in the cases
The electroreductive dehalogenation of of o-chlorophenyl or o-bromophenyl allyl
aromatic halides (489) and (491) with ethers (495) and the reduction of the Ar−Cl
Cl
DMF-Bu4NBF4-(Mg/Ni)
OCH2CH CH2 O
(495) (496)
Scheme 172 Cathodic cyclization of o-allyloxy-chlorobenzene.
EtOH/BuOH-aq.HCl/-SbCl3-(Pt/Pb)
R C Me R CH Me
6 F mol −1
O OH
(497) (498)
(498)R H Me MeO F Cl Br I
yield, % 99 73 42 91 94 98 94
Scheme 173 Antimony-mediated cathodic hydrogenation of aryl ketones.
Br
Bi(0) R CHO +
(499) (500)
e−
OH
Bi(III)
R
Cathode (501)
55~88% yield
R = p-Cl C6H4, Cyclohexyl, n-C8H17, Ph-CH = CMe
Scheme 174 Bismuth-catalyzed cathodic allylation of aldehydes.

or Ar−Br bond takes place instead, giving of SbCl3 (ca. 4.0 mol%) with passage of
the cyclized product (496) (Scheme 172). 6 F mol−1 of electricity. A possible mech-
Aliphatic aldehydes can be electrochemi- anism that accounts for the formation of
cally reduced faster than aryl allyl ethers to antimony hydride through the reduction
give the corresponding pinacols [573]. of Sb deposited on the electrode surface
by active hydrogen atoms has been pro-
15.3.9.2 Antimony (Sb) and Bismuth (Bi) posed [576].
Complex Mediators Because of lack of catalytic processes for
Antimony(III) trichloride can be used metals such as Sb and Bi (except for a few
as a catalytic mediator in the elec- cases) [530, 532], recycling of the metals in
troreduction of carbonyl compounds. multimediatory redox systems is of current
The advantage of the procedure is il- interest. Recently, allylation of aldehydes
lustrated by the selective reduction of (499) with (500) has been performed in
acetophenones (497), leading to the an aqueous CH2 Cl2 -BiCl3 -(Pt) two-phase
corresponding benzylic alcohols (498) system. Although the reaction (499→501)
(Scheme 173) [575]. The electroreduction can proceed in neutral solution, the
is performed in an EtOH/BuOH(1/1.5)- best result is obtained in acidic media
aq.HCl-(Pt/Pb) system in the presence (Scheme 174) [577].
G S SO2Ph G
Cl S
+2e−
N N
G Several O O
O OH
S steps
(a) (503) CO2PMB (504) CO2PMB
N
O
G S SO2Ph G
(502) CO2H S
+2e−
N • N
G = PhCH2CONH O O
PMB = p-CH3OC6H4CH2
CO2PMB CO2PMB
(b) (505) (506)
Scheme 175 Bismuth/tin-catalyzed cyclization of azetidin-2-one derivatives.
OH OH OH
OH
e− Cu(II) + +
e− (508) OH (510)
(509)
Cu(I) + O2
Cathode
(507)
Scheme 176 Cathodic production of phenol by copper(I)-catalyzed oxygenation of benzene.

A new electrolysis system comprising with dioxygen in the presence of Cu+

two metal redox couples, Bi(0)/Bi(III) and ions. The reaction can be operated con-
Al(0)/Al(III), has been shown to be ef- tinuously when the active Cu+ ions are
fective for electroreductive Barbier-type regenerated electrochemically [583]. The
allylation of imines [533]. The electrode electrolysis is carried out in an aq.
surface structure has been correlated with MeCN/H2 SO4 (0.1N)[1 : 9(v/v)] system in
the activity towards the electroreduction the presence of copper sulfate in a divided
of hydrogen peroxide for Bi monolayers cell. The reaction is highly pH-dependent,
on Au(III) [578]. Electroreductive cycliza- and pH control during electrolysis is
tion of the 4-(phenylsulfonylthio)azetidin- essential.
2-one derivative (502) as well as the The electroreduction of CO2 using a Cu
allenecarboxylate (505) leading to the cathode leads preferentially to methane
corresponding cyclized compounds (504) and ethane [584, 585]. The selectivity is
and (506) has been achieved with the aid dependent on the cationic species as well
of bimetallic metal salt/metal redox sys- as on the HCO3 − concentration [586].
tems, for example, BiCl3 /Sn and BiCl3 /Zn Hydrogen evolution prevails over CO2
(Scheme 175) [579]. The electrolysis of reduction in a Li+ electrolyte, whereas CO2
(502) is carried out in a DMF-BiCl3 /Py- reduction proceeds favorably in Na+ , K+ ,
(Sn/Sn) system in an undivided cell by and Cs+ solutions [587–589].
changing the current direction every 30 s,
giving the product (504)in 67% yield.
References
15.3.9.3 Copper (Cu) Complex Mediators

1. R. Clarke, A. Kuhn, E. Okoh, Chem. Br.
Since the catalytic effect of Cu2+ ions with
1975, 11, 59.
Fenton’s reagent has been recognized, 2. T. Osa, J. Synth. Org. Chem. Jpn. 1979, 37,
continuing interest has been focused on 361.
the role of the Cu species in oxidizing 3. S. Torii, T. Shiroi, J. Synth. Org. Chem. Jpn.
systems. The electrochemical alkyltransfer 1979, 37, 914.
reaction of trialkylboranes to carbonyl 4. T. Shono, Gendai Kagaku 1980, 24.
5. S. Torii, Syokubai 1980, 22, 330.
compounds has been performed in an 6. J. Y. Becker in The Chemistry of Functional
undivided cell by using the sacrificial Groups, Supplement D (Eds.: S. Patai et al.),
Cu anode in a DMF-Bu4 NI system, John Wiley & Sons, 1983, p. 203.
giving the alkylated products in 62∼77% 7. T. Shono, Tetrahedron 1984, 40, 811.
yields [580]. 8. S. Torii, Yukidenkaigosei, Kodansha, Tokyo,
1981.
Phenol (508) is found to be produced
9. T. Shono, Electroorganic Chemistry as a New
continuously from benzene (507) by aerial Tool in Organic Synthesis, Springer-Verlag,
oxidation in aqueous sulfuric acid when Berlin, Heidelberg, 1984.
a Cu(I)/Cu(II) redox couple is used as a 10. S. Torii, Electroorganic Syntheses Part I, Ox-
mediator (Scheme 176) [581]. The Cu(I)- idation Methods and Applications, Verlag
mediated electroreduction of oxygen in Chemie, Weinheim, Germany, 1985.
11. S. Torii, Synthesis 1986, 873.
the presence of chloride is found to be
12. A. J. Fry, Synthetic Organic Electrochemistry,
effective for toluene oxidation, leading to John Wiley & Sons, New York, 1989, p. 290.
benzaldehyde and benzyl chloride [582]. 13. Y. Matsumura, Kagaku to Kogyo 1990, 43,
Recently, benzene has also been oxidized 1972.
14. M. Tokuda, H. Suginome, Kagaku to Kogyo 37. T. Shono, Y. Matsumura, K. Tsubata et al.,
1990, 43, 1980. J. Org. Chem. 1989, 54, 2249.
15. T. Fuchigami, Yukagaku 1990, 39, 180. 38. T. Fujita, T. Fuchigami, Tetrahedron Lett.
16. S. Torii in Future Opportunities in Catalytic 1996, 37, 4725.
and Separation Technology (Eds.: M. Misono 39. I. Matsuura, T. Ueda, N. Murakami et al., J.
et al.), Elsevier, 1990, p. 323. Chem. Soc., Chem. Commun. 1992, 828.
17. S. Torii in Organic Synthesis in Japan – Past, 40. H. Maekawa, Y. Ishino, I. Nishiguchi,
Present, and Future (Ed.: R. Noyori), Tokyo Chem. Lett. 1994, 23, 1017.
Kagaku Dozin, Tokyo, 1992, pp. 481–486. 41. T. Shono, Y. Matsumura, J. Hayashi et al.,
18. S. Torii et al. in Electroorganic Synthesis J. Org. Chem. 1985, 50, 4968.
(Eds.: R. D. Little, N. L. Weinberg), Marcel 42. K. Fujimoto, H. Maekawa, Y. Matsubara
Dekker, New York, 1991, p. 249. et al., Chem. Lett. 1996, 25, 143.
19. S. Torii, J. Synth. Org. Chem. Jpn. 1993, 51, 43. T. C. Chou, J. J. Jaw, S. T. Yu, Chem. Eng.
1024. Commun. 1986, 42, 191.
20. A. S. Torii, Novel Trends in Electroorganic 44. T. C. Chou, J. S. Do, B. J. Hwang et al., J.
Synthesis, Kodansha, Tokyo, 1995. Chim Inst. Chem. Eng. 1988, 19, 1.
21. S. Torii, Interface 1997, 6, 46. 45. J. Nokami, M. Osafune, S. Sumida in Novel
22. S. Torii, Novel Trends in Electroorganic Trends in Electroorganic Synthesis (Ed.:
Synthesis, Springer, Tokyo, 1998. S. Torri), Springer, Tokyo, 1998, p. 127.
23. S. Torii in New Challenges in Organic 46. J. Nokami, M. Osafune, Y. Ito et al., Chem.
Electrochemistry (Ed.: T. Osa), Gorden & Lett. 1999, 28, 1053.
Breach Science Publishers, 1998, p. 113. 47. G. Palmisano, B. Danieli, M. Santagostino
24. H. Lund, O. Hammerich, Organic Electro- et al., Tetrahedron Lett. 1992, 33, 7779.
chemistry, Marcel Dekker, New York, 2001. 48. M. Kimura, S. Matsubara, Y. Yamamoto
25. F. Fichter, Organische Elektrochemie, Stein- et al., Tetrahedron 1991, 47, 867.
kopff, re-issued Salford University Book- 49. S. Torii, H. Tanaka, M. Ukida, J. Org. Chem.
shop, Leipzig, 1970, p. 75. 1979, 44, 1554.
26. A. J. Bard (Ed.), Encyclopedia of Electrochem- 50. S. Torii, H. Tanaka, S. Hamano et al.,
istry of the Elements, Marcel Dekker, New Chem. Lett. 1984, 13, 1823.
York, 1974, p. 326, Vol. 11. 51. S. Torii, H. Tanaka, N. Sayo, J. Org. Chem.
27. S. G. Dighe, J. Indian Chem. Soc. 1946, 23, 1979, 44, 2938.
291. 52. S. Torii, K. Uneyama, M. Ono et al., Tetra-
28. N. Ibl, K. Kramern, L. Ponto et al., AIChE hedron Lett. 1979, 20, 4661.
Symp. Ser. 1979, 75(185), 45. 53. S. Torii, K. Uneyama, S. Matsunami, J. Org.
29. W. M. Latimer, Oxidation Potentials, Pren- Chem. 1980, 45, 16.
tice Hall, New York, 1962, p. 339. 54. S. Torii, K. Uneyama, K. Ueda, J. Org.
30. R. Parsons, Handbook of Electrochemi- Chem. 1984, 49, 1830.
cal Constants, Butterworths, Markham, 55. J. Yoshida, J. Hashimoto, N. Kawabata, J.
Canada, 1959. Org. Chem. 1982, 47, 3575.
31. M. Pourbaix, Atlas of Electrochemical Equilib- 56. M. Yoshikawa, H. K. Wang, V. Tosirisuk
ria in Aqueous Solutions, Pergamon Press, et al., Chem. Pharm. Bull. 1982, 30, 3057.
New York, 1966. 57. S. Torii, K. Uneyama, M. Ono, Tetrahedron
32. K. Uneyama, M. Ono, S. Torii, Phosphorus Lett. 1980, 21, 2653.
Sulfur 1983, 16, 35. 58. S. Torii, K. Uneyama, M. Ono, Tetrahedron
33. S. Torii, H. Tanaka, M. Sasaoka et al., Bull. Lett. 1980, 21, 2741.
Soc. Chim. Belg. 1982, 91, 951. 59. S. Torii, K. Uneyama, K. Handa, Tetrahe-
34. S. Torii, H. Tanaka, M. Sasaoka et al., Denki dron Lett. 1980, 21, 1863.
Kagaku 1983, 51, 139 (presently Electro- 60. D. Pletcher, N. Tomov, J. Appl. Electrochem.
chemistry). 1977, 7, 501.
35. S. Torii, T. Inokuchi, S. Takagishi et al., 61. J. Yoshida, R. Nakai, N. Kawabata, J. Org.
Chem. Lett. 1987, 16, 1469. Chem. 1980, 45, 5269.
36. A. Papadopouls, B. Lewall, E. Steckhan 62. T. Shono, Y. Matsumura, S. Katoh et al., J.
et al., Tetrahedron 1991, 47, 563. Am. Chem. Soc. 1990, 112, 2368.
63. T. Shono, Y. Matsumura, K. Inoue et al., J. 90. W. Schmidt, E. Steckhan, Angew. Chem.,
Chem. Soc., Perkin Trans I 1986, 73. Int. Ed. Engl. 1979, 18, 801.
64. F. Barba, M. N. Elinson, J. Escudero et al., 91. W. Schmidt, E. Steckhan, Angew. Chem.,
Tetrahedron Lett. 1996, 37, 5759. Int. Ed. Engl. 1979, 18, 802.
65. F. Barba, M. N. Elinson, J. Escudero et al., 92. W. Schmidt, E. Steckhan, J. Electroanal.
Tetrahedron 1997, 53, 4427. Chem. 1978, 89, 215.
66. F. Barba, M. N. Elinson, J. Escudero et al., 93. W. Schmidt, E. Steckhan, Angew. Chem.,
Electrochim. Acta 1998 1997, 43, 973. Int. Ed. Engl. 1978, 17, 673.
67. T. Shono, Y. Matsumura, S. Katoh et al., 94. W. Schmidt, E. Steckhan, J. Electroanal.
Tetrahedron Lett. 1989, 30, 371. Chem. 1979, 101, 123.
68. M. Okimoto, T. Chiba, J. Org. Chem. 1993, 95. W. Schmidt, E. Steckhan, Chem. Ber. 1980,
58, 6194. 113, 577.
69. T. Chiba, H. Sakagami, M. Murata et al., J. 96. P. Martigny, J. Simonet, J. Electroanal.
Org. Chem. 1995, 60, 6764. Chem. 1980, 111, 133.
70. T. Chiba, I. Saitoh, M. Okimoto in Novel 97. D. Pletcher, G. D. Zappi, J. Electroanal.
Trends in Electroorganic Synthesis (Ed.: Chem. 1989, 270, 401.
S. Torri), Springer, Tokyo, 1998, p. 123. 98. K.-H. G. Brinkhaus, E. Steckhan, W. Sch-
71. T. Shono, Y. Matsumura, J. Hayashi et al., midt, Acta Chem. Scand. 1983, B37, 499.
Tetrahedron Lett. 1979, 165. 99. D. Pletcher, G. D. Zappi, J. Electroanal.
72. P. A. Garcia, R. Velasco, F. Barba, Synth. Chem. 1989, 265, 203.
Commun. 1991, 21, 1153. 100. J. E. Léonard, P. C. Scholl, T. P. Steckel,
73. L. L. Miller, B. F. Watkins, Tetrahedron Lett. Tetrahedron Lett. 1980, 21, 4695.
1974, 4495. 101. S. Kashimura, M. Ishifune, H. Maekawa
et al., Denki Kagaku 1997, 65, 479 (presently
74. T. Shono, Y. Matsumura, J. Hayashi et al.,
Electrochemistry).
Acta Chem. Scand. 1983, B37, 491.
102. T. Shono, Y. Yamamoto, K. Takigawa et al.,
75. T. Shono, Y. Matsumura, K. Inoue, J. Org.
Chem. Lett. 1994, 23, 1045.
Chem. 1986, 51, 549.
103. U. Wille, L. Lietzau, Tetrahedron 1999, 55,
76. S. Torii, N. Sayo, H. Tanaka, Tetrahedron
10 119.
Lett. 1979, 4471.
104. W. Li, T. Nonaka, Chem. Lett. 1997, 26, 1271.
77. G. F. Cosma, I. Radoi, Rev. Chim. 1993, 44,
105. S. D. Rychnovsky, R. Vaidyanathan, T. Be-
961. auchamp et al., J. Org. Chem. 1999, 64, 6745.
78. V. F. Pfeifer, V. E. Sohns, H. F. Conway 106. M. F. Semmelhack, C. S. Chou, D. A.
et al., Ind. Eng. Chem. 1960, 52, 201. Cortes, J. Am. Chem. Soc. 1983, 105, 4992.
79. A. Yoshiyama, T. Nonaka, M. M. Baizer 107. T. Inokuchi, S. Matsumoto, T. Nisiyama
et al., Bull. Chem. Soc. Jpn. 1985, 58, 201. et al., Synlett 1990, 57.
80. E. Steckhan, C. Kandzia, Synlett 1992, 139. 108. T. Inokuchi, S. Matsumoto, T. Nisiyama
81. T. Shono, Y. Matsumura, M. Mizoguchi et al., J. Org. Chem. 1991, 56, 2416.
et al., Tetrahedron Lett. 1979, 3861. 109. T. Inokuchi, P. Liu, S. Torii, Chem. Lett.
82. Y. Matsumura, M. Yamada, N. Kise et al., 1994, 23, 1411.
Tetrahedron 1995, 51, 6411. 110. Y. N. Ogibin, A. L. K. Khusid, G. T. Niki-
83. T. Shono, Y. Matsumura, M. Mizoguchi shin, Izv. Akad. Nauk, Ser. Khim. 1992, 941.
et al., Tetrahedron Lett. 1980, 21, 1867. 111. Y. N. Ogibin, I. S. Levina, A. V. Kamernit-
84. K. Chiba, Y. Yamaguchi, M. Tada, Tetrahe- sky et al., Mendeleev Commun. 1995, 184.
dron Lett. 1998, 39, 9035. 112. T. Osa, Y. Kashiwagi, K. Mukai et al., Chem.
85. D. S. Smith, J. Winnick, Y. Ding et al., Elec- Lett. 1990, 19, 75.
trochim. Acta 1998 1997, 43, 335. 113. Y. Kashiwagi, A. Ohsawa, T. Osa et al.,
86. M. Platen, E. Steckhan, Tetrahedron Lett. Chem. Lett. 1991, 20, 581.
1980, 21, 511. 114. Y. Yanagisawa, Y. Kashiwagi, F. Kurashima
87. M. Platen, E. Steckhan, Chem. Ber. 1984, et al., Chem. Lett. 1996, 25, 1043.
117, 1679. 115. E. M. Belgsir, H. J. Schäfer, Chem. Com-
88. M. Platen, E. Steckhan, Liebigs Ann. Chem. mun. 1999, 435.
1984, 1563. 116. Y. Kashiwagi, F. Kurashima, J.-I. Anzai
89. E. Steckhan, Top. Curr. Chem. 1987, 124, 1. et al., Heterocycles 1999, 51, 1945.
117. Y. Kashiwagi, F. Kurashima, C. Kikuchi 142. Y. Kashiwagi, Q. Pan, Y. Yanagisawa et al.,

et al., Tetrahedron. Lett. 1999, 40, 6469. Denki Kagaku 1994, 62, 1240 (presently
118. F. W. Hartstock, D. D. M. Wayner, Tetrahe- Electrochemistry).
dron Lett. 1994, 35, 8137. 143. H. P. Gogolin, H. Wendt, Chem.-Ing.-Tech.
119. J. Tsuji, M. Minato, Tetrahedron Lett. 1987, 1976, 48, 797.
28, 3683. 144. R. M. Engelbrecht, J. C. Hill, R. N. Moore,
120. M. Masui, T. Ueshima, S. Ozaki, J. Chem. U. S. Patent 3,726,914, 1973.
Soc., Chem. Commun. 1983, 479. 145. R. M. Engelbrecht, J. C. Hill, R. N. Moore,
121. M. Masui, T. Kawaguchi, S. Ozaki, J. Chem. U.S. Patent 3,714,003, 1973.
Soc., Chem. Commun. 1985, 1484. 146. E. Blasiak, L. Piszczek, W. Baranek, Przem.
122. M. Masui, S. Hara, S. Ozaki, Chem. Pharm. Chem. 1967, 46, 447.
147. C. J. Thatcher, U.S. Patent 1,397,562, 1921.
Bull. 1986, 34, 975.
148. M. S. V. Pathy, H. V. K. Udupa, Indian
123. L. K. Andreeva, L. A. Kheifits, T. P. Cherka-
Chem. J., Annu. 1970, 67.
sova et al., Ger. Offen. 2,221, 116, 1972.
149. H. Schulz, F. Beck, Angew. Chem., Int. Ed.
124. L.-M. Chen, Y.-L. Chen, T.-C. Chou, Denki
1985, 24, 1049.
Kagaku 1994, 62, 1173 (presently Electro- 150. J. M. Garrison, R. W. Lee, T. C. Bruice, In-
chemistry). org. Chem. 1990, 29, 2019.
125. T. M. Mohan, H. Gomathi, G. P. Rao, Bull. 151. T. Inokuchi, L. Ping, F. Hamaue et al.,
Electrochem. 1990, 6, 630. Chem. Lett. 1994, 23, 121.
126. M. Ishikawa, H. Okimoto, M. Morita et al., 152. H. Riering, H. J. Schäfer, Chem. Ber. 1994,
Chem. Lett. 1996, 25, 953. 127, 859.
127. I. P. Chernobaev, V. M. Khalabudenko, Zh. 153. D. G. Miller, D. D. M. Wayner, Can. J.
Prikl. Khim. 1975, 48, 819. Chem. 1992, 70, 2485.
128. D. A. Issahary, G. Ginzburg, M. Polak et al., 154. D. D. M. Wayner, F. W. Hartstock, J. Mol.
J. Chem. Soc., Chem. Commun. 1982, 441. Catal. 1988, 48, 15.
129. R. Schneider, H. J. Schäfer, Synthesis 1989, 155. F. Goodridge, C. J. H. King, Trans. Faraday
742. Soc. 1970, 66, 2889.
130. J. Kaulen, H. J. Schäfer, Tetrahedron 1982, 156. J.-E. Backwall, A. Gogoll, J. Chem. Soc.,
38, 3299. Chem. Commun. 1987, 1236.
131. A. Bewick, D. Coe, J. M. Mellor, Synth. 157. F. W. Hartstock, D. G. Derrington, L. B.
Commun. 1981, 11, 133. McMahon, Tetrahedron Lett. 1994, 35, 8761.
132. M. Onishi, K. Hiraki, Y. Ishida et al., Chem. 158. M. Fleischmann, D. Pletcher, G. M. Race,
Lett. 1986, 15, 333. J. Electroanal. Chem. Interfacial Electrochem.
133. J. C. Farmer, F. T. Wang, P. R. Lewis et al., 1969, 23, 369.
J. Electrochem. Soc. 1992, 139, 3025. 159. M. S. Thompson, W. F. De Giovani, B. A.
134. Y. Hisaeda, Novel Trends Electroorg. Synth. in Moyer et al., J. Org. Chem. 1984, 49, 4972.
Novel Trends in Electroorganic Synthesis (Ed.: 160. L. Roecker, T. J. Meyer, J. Am. Chem. Soc.
1987, 109, 746.
S. Torri), Springer, Tokyo, 1998, p. 399.
161. B. A. Moyer, M. S. Thompson, T. J. Meyer,
135. J. Wellmann, E. Steckhan, Chem. Ber. 1977,
J. Am. Chem. Soc. 1980, 102, 2310.
110, 3561.
162. M. S. Thompson, T. J. Meyer, J. Am. Chem.
136. C. Walling, R. A. Johnson, J. Am. Chem.
Soc. 1982, 104, 4106.
Soc. 1975, 97, 363. 163. J. C. Dobson, W. K. Seok, T. J. Meyer, In-
137. T. Matsue, M. Fujihira, T. Osa, J. Elec- org. Chem. 1986, 25, 1513.
trochem. Soc. 1981, 128, 2565. 164. W. K. Seok, T. J. Meyer, J. Am. Chem. Soc.
138. M. H. Liu, C. Yu Yeh, Y. Oliver Su, J. Chem. 1988, 110, 7358.
Soc., Chem. Commun. 1996, 1437. 165. S. Torii, T. Inokuchi, T. Yukawa, Chem.
139. I. Suzuki, Q. Chen, Y. Kashiwagi et al., Lett. 1984, 13, 1063.
Chem. Lett. 1993, 22, 1719. 166. S. Torii, T. Inokuchi, T. Yukawa, Heterocy-
140. J. Komoschinski, E. Steckhan, Tetrahedron cles 1984, 21, 652.
Lett. 1988, 29, 3299. 167. M.-L. Tsai, T.-C. Chou, Denki Kagaku 1994,
141. E. Liaudet, F. Battaglini, E. J. Calvo, J. Elec- 62, 1169 (presently Electrochemistry).
troanal. Chem. 1990, 293, 55. 168. E. D. Wilhoit, U.S. Patent 5,236,561, 1993.
169. S. Torii, T. Inokuchi, T. Sugiura, J. Org. 196. R. Shundo, I. Nishiguchi, Y. Matsubara

Chem. 1986, 51, 155. et al., Chem. Lett. 1990, 19, 2285.
170. S. Rajendran, D. C. Trivedi, Synthesis 1995, 197. T. Okabe, E. Narita, Y. Kobayashi et al., Ger.
153. Offen 2,514,184, 1976.
171. S. Torii, T. Inokuchi, S. Matsumoto et al., 198. A. V. Liven, A. M. Egorov, A. M. Vladimirt-
Bull. Chem. Soc. Jpn. 1989, 62, 2108. sev et al., U.S.S.R. Patent 238,538, 1967.
172. T. Inokuchi, S. Tanigawa, M. Kanazaki 199. A. Gref, G. Balavoine, H. Riviere et al.,
et al., Synlett 1991, 707. Nouv. J. Chim. 1984, 8, 615.
173. S. Torii, T. Inokuchi, S. Matsumoto, 200. S. Chidambaram, M. S. V. Pathy, H. V. K.
T. Saeki, T. Oki, Bull. Chem. Soc. Jpn. 1990, Udupa, J. Electrochem. Soc. India 1968, 17,
63, 852. 95.
174. S. Chocron, M. Michman, J. Mol. Catal. 201. R. Ramaswamy, M. S. Venkatachalapathy,
1991, 66, 85. H. V. K. Udupa, J. Electrochem. Soc. 1963,
175. J. M. Madurro, G. Chiericato Jr., W. F. De 110, 202.
Giovani et al., Tetrahedron Lett. 1988, 29, 202. H. V. K. Udupa, M. S. Venkatachalapathy,
765. Indian Patent 66,175, 1960.
176. J. L. Campos, W. F. De Giovani, J. R. 203. H. V. K. Udupa, M. S. Venkatachalapathy,
Romero, Synthesis 1990, 597. R. Ramaswamy, Indian Patent 62,379, 1959.
177. M. Navarro, W. F. De Giovani, J. R. Romero, 204. R. A. C. Rennie, Ger. Offen. 1,804,728,
Synth. Commun. 1990, 20, 399. 1972.
178. M. Navarro, W. F. De Giovani, J. R. Romero, 205. R. Ramaswamy, M. S. Venkatachalapathy,
Tetrahedron 1991, 47, 851. H. V. K. Udupa, Bull. Chem. Soc. Jpn. 1962,
179. S. Torii, T. Inokuchi, Y. Hirata, Synthesis 35, 1751.
1987, 377.
206. M. A. Dombroshi, S. A. Kates, B. B. Snider,
180. E. Steckhan, C. Kandzia, Synlett 1992, 139.
J. Am. Chem. Soc. 1990, 112, 2759.
181. S. Cosnier, A. Deronzier, J.-F. Roland, J.
207. B. B. Snider, J. J. Patricia, J. Org. Chem.
Mol. Catal. 1992, 71, 303.
1989, 54, 38.
182. S. Torii, A. Yoshida, Chem. Lett. 1995, 24,
208. K. Nohair, I. Lachaise, J. P. Paugam et al.,
369.
Tetrahedron Lett. 1992, 33, 213.
183. J. S. Mayell, Ind. Eng. Chem. Prod. Res. Dev.
209. J. Y. Nédélec, K. Nohair, Synlett 1991, 659.
1968, 7, 129.
184. S. Torii, P. Liu, H. Tanaka, Chem. Lett. 1995, 210. K. S. Rangappa, N. Anitha, M. A. Nikath
24, 319. et al., Asian J. Chem. 1999, 11, 401.
185. S. Torii, P. Liu, N. Bhuvaneswari et al., J. 211. M. A. Nikath, N. Anitha, K. M. L. Rai et al.,
Org. Chem. 1996, 61, 3055. Trends Carbohydr. Chem. 1999, 4, 109.
186. S. Torii, Electrochem. Soc. Interface 1997, 6, 212. S. Chandraju, K. S. Rangappa, Oxid. Com-
46. mun. 1999, 22, 448.
187. H. Tanaka, R. Kikuchi, M. Baba et al., Bull. 213. T. C. Chou, C. H. Cheng, J. Appl. Elec-
Chem. Soc. Jpn. 1995, 68, 2989. trochem. 1992, 22, 743.
188. W. Lang, U.S. Patent 808,095, 1905. 214. Z. Ogumi, T. Mizoe, C. Zhen et al., Bull.
189. W. Lang, Ger. Offen. 189,178, 1902. Chem. Soc. Jpn. 1990, 63, 3365.
190. M. Kagami, K. Kushibe, Japanese Patent 215. T.-L. Ho, Synthesis 1973, 347.
Kokai 48-28442, 1973. 216. T. A. Beomele, J. Delgaudio, Inorg. Chem.
191. M. S. Venkatachalapathy, R. Ramaswamy, 1968, 7, 715.
H. V. K. Udupa, Bull. Acad. Polon. Sci., Ser. 217. A. R. Al-Karaghoouli, J. S. Wood, J. Chem.
Sci. Chim. 1960, 8, 361. Soc., Chem. Commun. 1970, 135.
192. F.-T. Su, W.-C. Chen, Union Ind. Res. Inst. 218. L. Kohman, M. Perec, Przem. Chem. 1965,
Rep. 1957, 29, 11. 44, 239.
193. J. P. Coleman, R. C. Hallcher, D. E. McMac- 219. S. Torii, H. Tanaka, T. Inokuchi et al., J.
kins et al., Tetrahedron 1991, 47, 809. Org. Chem. 1982, 47, 1647.
194. R. Shundo, Y. Matsubara, I. Nishiguchi 220. T. Ishino, J. Shiokawa, Technol. Rep. Osaka
et al., Chem. Express 1991, 6, 547. Univ. 1960, 10, 261.
195. R. Shundo, I., Nishiguchi, Y. Matsubara 221. M. Morita, T. Masatani, Y. Matsuda, Bull.
et al., Tetrahedron 1991, 47, 831. Chem. Soc. Jpn. 1993, 66, 2747.
222. C. Rol, G. V. Sebastiani, J. Chem. Res. (S) 247. R. Favier, C. Frappel, J. C. Riher et al., Can.
1991, 194. J. Chem. 1971, 49, 2590.
223. M. Morita, S. Kitamura, M. Ishikawa et al., 248. J. Vojtko, M. Hrusovsky, M. Chihova et al.,
Denki Kagaku 1994, 62, 1206 (presently Czech. Patent 161,439, 1975.
Electrochemistry). 249. T. Shono, Tetrahedron 1984, 40, 811.
224. H. Wang, G. Wang, Qingdao Huagong 250. S. Torii, T. Inokuchi, J. Synth. Org. Chem.
Xueyuan Xuebao 1997, 18, 128. Jpn. 1985, 533.
225. G. Boulanger, D. Ducharme, M. Petitclerc 251. J. Simonet, G. Le Guillanton, Bull. Soc.
et al., Denki Kagaku 1994, 62, 1217 Chim. Fr. 1985, 180.
(presently Electrochemistry). 252. F. Petit, Bull. Soc. Chim. Fr. 1985, 203.
226. G. Kreysa, H. Medin, J. Appl. Electrochem. 253. H. Lehmkuhl, W. Leuchte, W. Eisenbach,
1986, 16, 757. Liebigs Ann. Chem. 1973, 692.
227. M. Matsuoka, Y. Kokusenya, Japanese 254. K. P. Healy, D. Pletcher, J. Organomet.
Patent Kokai 50-144697, 1975. Chem. 1978, 161, 109.
228. Y. Matsuda, M. Morita, H. Tsutsumi et al., 255. G. Bontempelli, F. Mango, G. Schiavon
Japanese Patent Kokai 05-98481, 1993. et al., Inorg. Chem. 1981, 20, 2579.
229. Y. Matsuda, M. Morita, H. Tsutsumi et al., 256. H. Lehmkuhl, K. Mehler, G. Hauschild,
Japanese Patent Kokai 05–98482, 1993. Chem. Ber. 1983, 116, 438.
230. Y. Nakamura, Nippon Kagaku Kaishi 1982, 257. C. Gosden, K. P. Healy, D. Pletcher, J.
1727. Chem. Soc., Dalton Trans. 1978, 972.
231. M. Marrocco, G. Brilmyer, J. Org. Chem. 258. A. L. Butler, D. G. Peters, J. Electrochem.
1983, 48, 1487. Soc. 1997, 144, 4212.
232. R. P. Kreh, R. M. Spotnitz, J. T. Lundquist, 259. M. Troupel, Y. Rollin, S. Sibille et al., J.
J. Org. Chem. 1989, 54, 1526. Chem. Res. (S) 1980, 24; (M) 1980, 173.
233. R. M. Spotnitz, R. P. Kreh, J. T. Lundquist 260. M. Troupel, R. Rollin, S. Sibille et al., J.
et al., J. Appl. Electrochem. 1990, 20, 209. Chem. Res. (S) 1980, 26.
234. J. V. Lavagnoli, J. M. Madurro, J. R. Rom- 261. M. Troupel, Y. Rollin, S. Sibille et al., J.
ero, Quim. Nova 1998, 21, 731. Chem. Res. (S) 1979, 50; (M) 1979, 601.
235. L. Y. Cho, J. R. Romero, Quim. Nova 1998, 262. M. Troupel, Y. Rollin, S. Sibille et al., J.
21, 144. Organomet. Chem. 1980, 202, 435.
236. R. A. C. Rennie, Ger. Offen. 1,804,727, 263. Y. Rollin, M. Troupel, J. Périchon et al., J.
1969. Chem. Res. (S) 1981, 322; (M) 1981, 3801.
237. R. Alkire, O. Araujo, J. Electrochem. Soc. 264. S. Sibille, M. Troupel, J.-F. Fauvarque et al.,
1992, 139, 737. J. Chem. Res. (S) 1980, 147; (M) 1980, 2201.
238. I. M. Dalrymple, J. P. Millington, J. Appl. 265. C. Amatore, A. Jutand, L. Mottier, J. Elec-
Electrochem. 1986, 16, 885. troanal. Chem. 1991, 306, 125.
239. T. Koyama, A. Kitani, S. Ito et al., Chem. 266. V. Courtois, R. Barhdadi, M. Troupel et al.,
Lett. 1993, 22, 395. Tetrahedron 1997, 53, 11 569.
240. S. Ito, M. Iwata, A. Kitani et al., Denki 267. C. Gosmini, S. Lasry, J. Y. Nédélec et al.,
Kagaku 1994, 62, 1221 (presently Electro- Tetrahedron 1998, 54, 1289.
chemistry). 268. S. Sibille, J.-C. Folest, J. Coulombeix et al.,
241. C. Kandzia, E. Steckhan, Tetrahedron Lett. J. Chem. Res. (S) 1980, 268.
1994, 35, 3695. 269. J.-F. Fauvarque, Y. De Zelicourt, C. Ama-
242. S. Ito, M. Iwata, K. Sasaki, Tetrahedron tore et al., J. Appl. Electrochem. 1990, 20,
1997, 47, 841. 338.
243. A. Paire, D. Espinoux, M. Masson et al., 270. M. A. Fox, D. A. Chandler, C. Lee, J. Org.
Radiochim. Acta 1997, 78, 137. Chem. 1991, 56, 3246.
244. M. Sharp, D. D. Montgomery, F. C. Anson, 271. J.-F. Fauvarque, C. Chêvrot, A. Jutand et al.,
J. Electroanal. Chem. 1985, 194, 247. J. Organomet. Chem. 1984, 264, 273.
245. A. F. MacLean, A. L. Stautzenberger, U.S. 272. C. Amatore, A. Jutand, J. Electroanal. Chem.
Patent 3,479,262, 1969. 1991, 306, 141.
246. F. Goodridge, C. J. H. King, J. Appl. Chem. 273. C. Amatore, A. Jutand, L. Mottier, J. Elec-
Biotechnol. 1971, 21, 208. troanal. Chem. 1991, 306, 125.
274. G. Silvestri, S. Gambino, G. Filardo et al., 301. S. Sibille, E. d’Incan, L. Leport et al., Tetra-
Angew. Chem., Int. Ed. Engl. 1984, 23, 979. hedron Lett. 1987, 28, 55.
275. O. Sock, M. Troupel, J. Périchon, Tetrahe- 302. S. Durandetti, S. Sibille, J. Périchon, J. Org.
dron Lett. 1985, 26, 1509. Chem. 1989, 54, 2198.
276. J.-F. Fauvarque, A. Jutand, M. Français, 303. S. Mcharek, S. Sibille, J. Y. Nédélec, J.
Nouv. J. Chim. 1986, 10, 119. Organomet. Chem. 1991, 401, 211.
277. J.-F. Fauvarque, J. Appl. Electrochem. 1988, 304. M. Tokuda, S. Satoh, Y. Katoh et al., Elec-
18, 109. troorg. Synth. 1991, 83.
278. C. Amatore, A. Jutand, J. Am. Chem. Soc. 305. A. M. Stolzenberg, M. T. Stershic, J. Am.
1991, 113, 2819. Chem. Soc. 1988, 110, 5397.
279. M. Mori, Y. Hashimoto, Y. Ban, Tetrahe- 306. A. Bakac, J. H. Espenson, J. Am. Chem. Soc.
dron Lett. 1980, 21, 631. 1986, 108, 5353.
280. T. Komura, T. Terashima, K. Takahashi, 307. J. Y. Becker, J. B. Kerr, D. Pletcher et al., J.
Denki Kagaku 1991, 59, 780. Electroanal. Chem., Interfacial Electrochem.
281. J.-F. Fauvarque, A. Digua, M.-A. Petit et al., 1981, 117, 87.
Makromol. Chem. 1985, 186, 2415. 308. S. Ozaki, T. Nakanishi, M. Sugiyama et al.,
282. N. W. Alcock, P. N. Bartlett, V. M. Eastwick- Chem. Pharm. Bull. 1991, 39, 31.
Field et al., J. Mater. Chem. 1991, 1, 569. 309. S. Sibille, J. Coulombeix, J. Périchon et al.,
283. A. Siove, D. Ades, C. Chêvrot, Makromol. J. Mol. Catal. 1985, 32, 239.
Chem. 1989, 190, 1361. 310. M. Troupel, Y. Rollin, G. Meyer et al., Nouv.
284. M. Troupel, Y. Rollin, J. Périchon, Nouv. J. J. Chim. 1985, 9, 487.
Chim. 1981, 5, 621. 311. Y. Rollin, M. Troupel, G. Meyer et al., J.
285. S. Ozaki, E. Matsui, J. Waku et al., Tetrahe- Electroanal. Chem. Interfacial Electrochem.
dron Lett. 1997, 38, 2705. 1985, 183, 247.
286. S. Ozaki, H. Matsushita, H. Ohmori, J. 312. G. Bontempelli, S. Daniele, G. Schiavon
Chem. Soc., Chem. Commun. 1992, 1120. et al., Transition Met. Chem. 1987, 12, 292.
287. S. Ozaki, H. Matsushita, H. Ohmori, J. 313. E. Duñach, J. Périchon, Synlett 1990, 143.
Chem. Soc., Perkin Trans. I 1993, 649. 314. E. Duñach, J. Périchon, J. Organomet.
288. S. Condon-Gueugnot, E. Léonel, J. Y. Chem. 1988, 352, 239.
Nédélec et al., J. Org. Chem. 1995, 60, 7684. 315. E. Labb, E. Duñach, J. Périchon, J. Organo-
289. S. Ozaki, I. Horiguchi, H. Matsushita et al., met. Chem. 1988, 353, C51.
Tetrahedron Lett. 1994, 35, 725. 316. S. Dérien, E. Duñach, J. Périchon, J. Am.
290. M. S. Mubarak, D. G. Peters, J. Electroanal. Chem. Soc. 1991, 113, 8447.
Chem. 1992, 332, 127. 317. S. Dérien, J.-C. Clinet, E. Duñach et al., J.
291. M. Troupel, Y. Rollin, O. Sock et al., Nouv. Chem. Soc., Chem. Commun. 1991, 549.
J. Chim. 1986, 10, 593. 318. S. Dérien, E. Duñach, J. Périchon, J. Org.
292. Y. Rollin, G. Meyer, M. Troupel et al., J. Chem. 1990, 385, C43.
Chem. Soc., Chem. Commun. 1983, 793. 319. S. Dérien, J.-C. Clinet, E. Duñach et al., J.
293. S. Olivero, J. C. Clinet, E. Duñach, Tetrahe- Org. Chem. 1993, 58, 2578.
dron Lett. 1995, 36, 4429. 320. S. Dérien, J.-C. Clinet, E. Duñach, J. Péri-
294. A. Conan, S. Sibille, E. d’Incan et al., J. chon, Tetrahedron 1992, 48, 5235.
Chem. Soc., Chem. Commun. 1990, 48. 321. S. Olivero, E. Duñach, Eur. J. Org. Chem.
295. A. Conan, S. Sibille, J. Périchon, J. Org. 1999, 1885.
Chem. 1991, 56, 2018. 322. H. Senboku, Y. Fujimura, A. Yoshikawa
296. M. Durandetti, S. Sibille, J. Y. Nédélec et al., et al. in Novel Trends in Electroorganic Syn-
Synth. Commun. 1994, 24, 145. thesis (Ed.: S. Torri), Springer, Tokyo, 1998,
297. S. Mcharek, S. Sibille, J. Y. Nédélec et al., J. p. 243.
Organomet. Chem. 1991, 401, 211. 323. M. Tokuda, H. Kamekawa, H. Senboku in
298. V. Courtois, R. Barhdadi, S. Condon et al., Novel Trends in Electroorganic Synthesis (Ed.:
Tetrahedron Lett. 1999, 40, 5993. S. Torri), Springer, Tokyo, 1998, p. 239.
299. M. Durandetti, J. Périchon, J. Y. Nédélec, 324. T. Chiba, M. Okimoto, H. Nagai et al., Bull.
Tetrahedron Lett. 1997, 38, 8683. Chem. Soc. Jpn. 1983, 56, 719.
300. C. Gosmini, J. Y. Nédélec, J. Périchon, 325. L. Garnier, Y. Rollin, J. Périchon, J. Organo-
Tetrahedron Lett. 1997, 38, 1941. met. Chem. 1989, 367, 347.
326. E. Dolhem, M. Ocafrain, J. Y. Nédélec et al., 353. T. R. O’Toole, L. D. Margerum, T. D. West-

Tetrahedron 1997, 53, 17 089. moreland et al., J. Chem. Soc., Chem.
327. P. Tascedda, E. Duñach, J. Chem. Soc., Commun. 1985, 1416.
Chem. Commun. 1995, 43. 354. B. P. Sullivan, C. M. Bolinger, D. Conrad
328. M. Ocafrain, M. Devaud, M. Troupel et al., et al., J. Chem. Soc., Chem. Commun. 1985,
J. Chem. Soc., Chem. Commun. 1995, 2331. 1414.
329. E. Léonel, J. P. Paugam, M. Heintz et al., 355. I. Taniguchi, T. Shimpuku, K. Yamashita
Synth. Commun. 1999, 29, 4015. et al., J. Chem. Soc., Chem. Commun. 1990,
330. C. Amatore, J. M. Savéant, J. Am. Chem. 915.
Soc. 1981, 103, 5021. 356. ER98134 D. Franco, S. Olivero, J. P. Rolland
331. M. Beley, J.-P. Collin, R. Ruppert et al., J. et al., Novel Trends Electroorg. Synth., Pap.
Am. Chem. Soc. 1986, 108, 7461. Int. Symp., 3rd 1997, 1998, 391.
332. M. Beley, J.-P. Collin, R. Ruppert et al., J. 357. S. Olivero, E. Duñach, Synlett 1994, 531.
Chem. Soc., Chem. Commun. 1984, 1315. 358. S. Olivero, E. Duñach, J. Chem. Soc., Chem.
333. K. Hiratsuka, K. Takahashi, H. Sasaki et al., Commun. 1995, 2497.
Chem. Lett. 1977, 6, 1137. 359. V. V. Yanilkin, N. I. Maksimyuk, E. I.
334. K. Takahashi, K. Hiratsuka, H. Sasaki et al., Gritsenko et al., Izv. Akad. Nauk, Ser. Khim.
Chem. Lett. 1979, 8, 305. 1992, 292.
335. B. Fisher, R. Eisenberg, J. Am. Chem. Soc. 360. D. Franco, E. Duñach, Tetrahedron Lett.
1980, 102, 7361. 1999, 40, 2951.
336. M. Tezuka, T. Yajima, A. Tsuchiya et al., J. 361. S. Ozaki, E. Matsui, T. Saiki et al., Tetrahe-
Am. Chem. Soc. 1982, 104, 6834. dron Lett. 1998, 39, 8121.
337. J. Hawecker, J.-M. Lehn, R. Ziessel, J. 362. C. Iwakura, T. Abe, H. Inoue, Denki Kagaku
1997, 65, 1120.
338. C. M. Bolinger, B. P. Sullivan, D. Conrad
363. B. Mahdavi, P. Chambrion, J. Binette et al.,
et al., J. Chem. Soc., Chem. Commun. 1985,
Can. J. Chem. 1995, 73, 846.
796.
364. J. Pardillos-Guindet, S. Vidal, J. Court et al.,
339. S. Meshitsuka, M. Ichikawa, K. Tamaru, J.
J. Catal. 1995, 155, 12.
365. V. Beraud, J. Lessard, M. Thomalla, Can. J.
340. Research work of K. W. Frese, reported in
Chem. 1997, 75, 1529.
Chem. Eng. News 1985, July 8, p. 29.
341. A. Aramata, T. Atoguchi, A. Kazusaka et al., 366. S. J. C. Cleghorn, D. Pletcher, Electrochim.
Denki Kagaku 1992, 60, 565. Acta 1993, 38, 2683.
342. M. Fujihira, Y. Nakamura, Y. Hirata et al., 367. R. Scheffold, S. Abrecht, R. Orlinski et al.,
Denki Kagaku 1991, 532. Pure Appl. Chem. 1987, 59, 363.
343. M. G. Bradley, T. Tysak, D. J. Graves et al., 368. D. Zhou, O. Tinembart, R. Scheffold et al.,
J. Chem. Soc., Chem. Commun. 1983, 349. Helv. Chim. Acta 1990, 73, 2225.
344. K. Takahashi, K. Hiratsuka, H. Sasaki et al., 369. D.-L. Zhou, J. Gao, F. Rusling, J. Am. Chem.
Chem. Lett. 1979, 8, 305. Soc. 1995, 117, 1127.
345. M. Nakazawa, Y. Mizobe, Y. Matsumoto 370. R. Scheffold, E. Amble, Angew. Chem. 1980,
et al., Bull. Chem. Soc. Jpn. 1986, 59, 809. 92, 643.
346. K. Ogura, J. Appl. Electrochem. 1986, 16, 732. 371. R. Scheffold, E. Amble, Angew. Chem., Int.
347. T. Fukaya, M. Kodaka, M. Sugiura, Kagaku Ed. Engl. 1980, 19, 629.
Gijutsu Kenkyusho Hokoku 1986, 81, 255. 372. H.-F. Beer, R. Scheffold, Chimia 1987, 41,
348. H. Ishida, K. Tanaka, T. Tanaka, Organo- 67.
metallics 1987, 6, 181. 373. J. Gao, J. F. Rusling, D. Zhou, J. Org. Chem.
349. H. Ishida, K. Fujiki, T. Ohba et al., J. Chem. 1996, 61, 5972.
Soc., Dalton Trans. 1990, 2155. 374. R. Scheffold, M. Dike, S. Dike et al., J. Am.
350. A. Bandi, J. Electrochem. Soc. 1990, 137, Chem. Soc. 1980, 102, 3642.
2157. 375. B. Steiger, L. Walder, R. Scheffold, Ann.
351. H. Ishida, H. Tanaka, K. Tanaka et al., Chim. 1986, 40, 93.
Chem. Lett. 1987, 597. 376. R. Scheffold (Ed.), Modern Synthetic Meth-
352. J. Y. Becker, B. Vainas, R. Eger et al., J. ods, Otto Salle Verlag, Frankfurt 3, 355,
Chem. Soc., Chem. Commun. 1985, 1471. 1983.
377. B. Giese, Radicals in Organic Synthesis: For- 402. A. R. Guadalupe, D. A. Usifer, K. T. Potts
mation of Carbon – Carbon Bonds, Perga- et al., J. Am. Chem. Soc. 1988, 110, 3462.
mon Press, Oxford, 1986. 403. I. Taniguchi, N. Nakashima, K. Yasukouchi,
378. S. Busato, O. Tinembart, Z.-da Zhang, J. Chem. Soc., Chem. Commun. 1986, 1814.
R. Scheffold, Tetrahedron 1990, 46, 3155. 404. O. Ikeda, K. Okabayashi, H. Tamura, Chem.
379. Y. Murakami, Y. Hisaeda, S.-D. Fan, Chem. Lett. 1983, 12, 1821.
Lett. 1987, 16, 655. 405. D. W. Pang, Z. L. Wang, C. S. Cha, Elec-
380. Y. Murakami, Y. Hisaeda, T. Ozaki et al., trochim. Acta 1992, 37, 2591.
Bull. Chem. Soc. Jpn. 1987, 60, 311. 406. K. H. Schwarz, K. Kleiner, R. Ludwig et al.,
381. Y. Murakami, Y. Hisaeda, T. Tashiro et al., Chem. Ber. 1993, 126, 1247.
Chem. Lett. 1986, 15, 555. 407. F. Ojima, N. Kobayashi, T. Osa, Bull. Chem.
382. Y. Murakami, Y. Hisaeda, T. Tashiro et al., Soc. Jpn. 1990, 63, 1374.
Chem. Lett. 1985, 14, 1813. 408. K. Ogura, I. Yoshida, J. Mol. Catal. 1986, 34,
383. Y. Murakami, Y. Hisaeda, A. Kajihara et al., 67.
Bull. Chem. Soc. Jpn. 1984, 57, 405. 409. K. Ogura, Nippon Kagaku Kaishi 1986, 478.
384. Y. Murakami, Y. Hisaeda, S.-D. Gan et al., 410. R. Palanisamy, G. Sozhan, K. C. Narasim-
Bull. Chem. Soc. Jpn. 1989, 62, 2219. ham, Indian J. Technol. 1993, 31, 597.
385. Y. Murakami, Y. Hisaeda, T. Ozaki, J. Co- 411. K. Tanaka, R. Wakita, T. Tanaka, J. Am.
ord. Chem. 1991, 23, 77. Chem. Soc. 1989, 111, 2428.
386. T. Inokuchi, M. Tsuji, H. Kawafuchi et al., 412. K. Ogura, H. Watanabe, J. Chem. Soc.,
J. Org. Chem. 1991, 56, 5945. Faraday Trans. I 1985, 81, 1569.
387. J. F. Rusling, C. L. Miaw, E. C. Couture, In- 413. K. Ogura, M. Takagi, J. Electroanal. Chem.
org. Chem. 1990, 29, 2025. Interfacial Electrochem. 1986, 206, 209.
388. Y. Murakami, Y. Hisaeda, T. Ozaki et al., J. 414. K. Ogura, S. Yamasaki, J. Mol. Catal. 1985,
Chem. Soc., Chem. Commun. 1989, 1094. 30, 411.
389. A. Owlia, Z. Wang, J. F. Rusling, J. Am. 415. T. Tomohiro, Ko Uoto, H. Okuno, J. Chem.
Chem. Soc. 1989, 111, 5091. Soc., Chem. Commun. 1990, 194.
390. S. Torii, T. Inokuchi, T. Yukawa, J. Org. 416. N. Komeda, H. Nagao, T. Matui et al., J.
Chem. 1985, 50, 5875. Am. Chem. Soc. 1992, 114, 3625.
391. [ER94012]* T. Inokuchi, H. Kawafuchi, 417. C. Roger, C. Lapinte, J. Chem. Soc., Chem.
K. Aoki et al., Bull. Chem. Soc. Jpn. 1994, Commun. 1989, 1598.
67, 595. 418. K. Tanaka, M. Tanaka, T. Tanaka, Chem.
392. H. Bhandal, G. Pattenden, J. J. Russell, Lett. 1981, 895.
Tetrahedron Lett. 1986, 27, 2299. 419. M. H. Barley, K. Takeuchi, W. R. Murphy
393. P. Suisse, S. Pellegrini, Y. Castanet et al., J. et al., J. Chem. Soc., Chem. Commun. 1985,
Chem. Soc., Chem. Commun. 1995, 847. 507.
394. V. V. Yanilkin, N. I. Maksimyuk, E. I. 420. T. Sawaguchi, T. Matsue, K. Itaya et al.,
Gritsenko et al., Izv. Akad. Nauk, Ser. Khim. Electrochim. Acta 1991, 36, 703.
1992, 292. 421. J.-P. Battioni, D. Lexa, D. Mansuy et al., J.
395. A. J. Fry, U. N. N. Sirisoma, A. S. Lee, Am. Chem. Soc. 1983, 105, 207.
Tetrahedron Lett. 1993, 34, 809. 422. D. Huchette, J. Nicole, F. Petit, Tetrahedron
396. A. J. Fry, P. F. Fry, J. Org. Chem. 1993, 58, Lett 1979, 12, 1035.
3496. 423. D. Lexa, J.-M. Savéant, H. J. Schäfer et al.,
397. A. J. Fry, U. N. Sirisoma, J. Org. Chem. J. Am. Chem. Soc. 1990, 112, 6162.
1993, 58, 4919. 424. S. Kwee, Bioelectrochem. Bioenerg. 1986, 16,
398. A. J. Fry, A. H. Singh, J. Org. Chem. 1994, 99.
59, 8172. 425. Y. Matsuda, K. Nishi, T. Azuma, Denki
399. D. L. Zhou, J. Gao, J. F. Rusling, J. Am. Kagaku 1984, 52, 635.
Chem. Soc. 1995, 117, 1127. 426. T. Hirai, J. Yamaki, J. Electrochem. Soc.
400. T. Takiguchi, T. Nonaka, J. Electroanal. 1985, 132, 2125.
Chem. Interfacial Electrochem. 1988, 243, 427. J. M. Bauldreay, M. D. Archer, Electrochim.
393. Acta 1985, 30, 1355.
401. D. Sazou, C. Araullo-McAdams, B. C. Han 428. T. Bechtold, E. Burtcher, D. Gmeiner et al.,
et al., J. Am. Chem. Soc. 1990, 112, 7879. Melliand Textilber. 1991, 72, 50.
429. T. Bechtold, E. Burtcher, A. Amann et al., 455. S. Slater, J. H. Wagenknecht, J. Am. Chem.
Angew. Chem., Int. Ed. Engl. 1992, 31, 1068. Soc. 1984, 106, 5367.
430. M. H. Barley, K. Takeuchi, W. R. Murphy 456. J. A. Sofranko, R. Eisenberg, J. A. Kamp-
et al., J. Chem. Soc., Chem. Commun. 1985, meier, J. Am. Chem. Soc. 1979, 101, 1042.
507. 457. Y. Pottier, A. Mortreux, F. Petit, J. Organo-
431. C. J. Stalder, S. Chao, M. S. Wrighton, J. met. Chem. 1989, 370, 333.
Am. Chem. Soc. 1984, 106, 3673. 458. A. Mortreux, F. Petit, New Sci. Transition
432. D. L. DuBois, A. Miedaner, J. Am. Chem. Met. Catal. React., Adv. Chem. Ser. 1992,
Soc. 1987, 109, 113. 230, 261.
433. J. B. Davison, P. J. Peerce-Landers, R. J. 459. I. M. F. De Oliveira, J.-C. Moutet, J. Mol.
Jasinski, J. Electrochem. Soc. 1983, 130, 1862. Catal. 1993, 81, L19.
434. S. Torii, H. Tanaka, T. Katoh et al., Tetrahe- 460. S. Chardon-Noblat, I. M. F. De Oliveira,
dron Lett. 1984, 25, 3207. J.-C. Moutet et al., J. Mol. Catal. 1995, 99,
435. P. Zhang, W. Zhang, T. Zhang et al., J. 13.
Chem. Soc., Chem. Commun. 1991, 491. 461. Y. Kushi, H. Nagao, T., Nishioka et al.,
436. M. Minato, T. Nonaka, T. Fuchigami, Chem. Chem. Lett. 1994, 23, 2175.
Lett. 1986, 15, 1071. 462. R. Wienkamp, E. Steckhan, Angew. Chem.,
437. D. Franco, D. Panyella, M. Rocamora et al., Int. Ed. Engl. 1982, 21, 782.
Tetrahedron Lett. 1999, 40, 5685. 463. R. Ruppert, S. Herrmann, E. Steckhan, J.
438. C. Amatore, E. Blart, J. P. Genêt et al., J. Chem. Soc., Chem. Commun. 1988, 1150.
Org. Chem. 1995, 60, 6829. 464. K. Tanaka, Denki Kagaku 1990, 58, 989.
439. A. I. Tsyganok, I. Yamanaka, K. Otsuka, 465. H. Nagao, T. Mizukawa, K. Tanaka, Inorg.
Chem. Lett. 1998, 27, 303. Chem. 1994, 33, 3415.
440. S. Torii, H. Tanaka, K. Morisaki, Tetrahe-
466. M. M. Ali, H. Sato, T. Mizukawa et al., J.
dron Lett. 1985, 26, 1655.
441. C. Amatore, A. Jutand, Acta Chem. Scand.
467. K. Tanaka, Bull. Chem. Soc. Jpn. 1998, 71,
1990, 44, 755.
17.
442. C. Amatore, M. Azzabi, A. Jutand, J. Am.
468. H. Ishida, K. Tanaka, T. Tanaka, J. Elec-
Chem. Soc. 1991, 113, 8375.
trochem. Soc. 1985, 405.
443. C. Amatore, A. Jutand, A. Suarez, J. Am.
469. H. Nagao, T. Mizukawa, K. Tanaka, Inorg.
Chem. Soc. 1993, 115, 9531.
444. C. Amatore, E. Carré, A. Jutand et al., Chem. 1994, 33, 3415.
Organometallics 1995, 14, 5605. 470. M. M. Ali, H. Sato, T. Mizukawa et al.,
445. C. Amatore, E. Carré, A. Jutand et al., Chem. Commun. 1998, 249.
Chem. Eur. J. 1996, 2, 957. 471. G. Arai, T. Harashina, I. Yasumori, Chem.
446. C. Amatore, E. Carré, A. Jutand et al., Elec- Lett. 1989, 18, 1215.
trochim. Acta 1997, 42, 2143. 472. D. A. Buttry, F. C. Anson, J. Am. Chem. Soc.
447. S. Torii, H. Tanaka, T. Hamatani et al., 1984, 106, 59.
Chem. Lett. 1986, 15, 169. 473. C. Shi, F. C. Anson, J. Am. Chem. Soc. 1991,
448. A. Jutand, S. Négri, A. Mosleh, J. Chem. 113, 9564.
Soc., Chem. Commun. 1992, 1729. 474. J. P. Collman, J. E. Hutchison, M. A. Lopez
449. A. Jutand, S. Négri, Synlett 1997, 719. et al., J. Am. Chem. Soc. 1991, 113, 2794.
450. S. Torii, H. Tanaka, K. Morisaki, Chem. Lett. 475. D. W. Popes, T. J. Meyer, J. Am. Chem. Soc.
1985, 14, 1353. 1984, 106, 7653.
451. P. W. Wang, M. A. Fox, J. Org. Chem. 1994, 476. S. Torii, P. Liu, H. Tanaka, Chem. Lett. 1995,
59, 5358. 24, 319.
452. Y. B. Vassiliev, V. S. Bagotzky, N. V. Ose- 477. J. Wellmann, E. Steckhan, Synthesis 1978,
trova et al., J. Electroanal. Chem. Interfacial 901.
Electrochem. 1985, 189, 311. 478. C. Gosmini, J. Y. Nédélec, J. Périchon,
453. J. B. Kerr, L. L. Miller, M. R. Van De Mark, Tetrahedron Lett. 2000, 41, 201.
J. Am. Chem. Soc. 1980, 102, 3383. 479. M. Kuroboshi, M. Tanaka, S. Kishimoto
454. G. Pilloni, E. Vecchi, M. Martelli, J. Elec- et al., Synlett 1999, 69.
troanal. Chem. Interfacial Electrochem. 1973, 480. M. Durandetti, J. Périchon, J. Y. Nédélec,
45, 483. Tetrahedron Lett. 1999, 40, 9009.
481. P. H. Given, M. E. Peover, Collect. Czech. 505. N. Kobayashi, Y. Nishiyama, J. Phys. Chem.
Chem. Commun. 1960, 25, 3195. 1985, 89, 1167.
482. D. W. Sopher, J. H. P. Utley, J. Chem. Soc., 506. N. Kobayashi, H. Saiki, T. Osa, Chem. Lett.
Chem. Commun. 1979, 1087. 1985, 14, 1917.
483. D. W. Sopher, J. H. P. Utley, J. Chem. Soc., 507. S. E. Creager, S. A. Raybuck, R. W. Murray,
Perkin Trans. 2 1984, 1361. J. Am. Chem. Soc. 1986, 108, 4225.
484. M. Perrin, P. Pouillen, G. Mousset et al., 508. H. Nishihara, K. Pressrich, R. W. Murray
Tetrahedron 1980, 36, 221. et al., Inorg. Chem. 1990, 29, 1000.
485. F. Fournier, J. Berthelot, Y.-L. Pascal, Can. 509. C. P. Horwitz, S. E. Creager, R. W. Murray,
J. Chem. 1983, 61, 2121. Inorg. Chem. 1990, 29, 1006.
486. K. Takeuchi, T. Kurosaki, Y. Yokomichi 510. Y. Suzuki, Y. Koseki, K. Takahashi et al.,
et al., J. Chem. Soc., Perkin Trans. 2 1981, Bull. Chem. Soc. Jpn. 1994, 67, 847.
670. 511. B. A. Narayanan, C. Amatore, C. P. Casey
487. A. A. Vasil’ev, V. I. Tatarinova, V. A. Petros- et al., J. Am. Chem. Soc. 1983, 105, 6351.
yan, Mendeleev Commun. 1993, 27. 512. D. W. Pipes, T. J. Meyer, J. Am. Chem. Soc.
488. C. Hackmann, H. J. Schäfer, Tetrahedron 1985, 107, 7201.
1993, 49, 4559. 513. J. Chaussard, L’actualit* Chimique 1982, 9,
489. R. Wolf, E. Steckhan, J. Chem. Soc., Perkin 29.
Trans I 1986, 733. 514. M. Noel, P. N. Anantharaman, H. V.
490. D. Pletcher, J. C. P. White, Electrochim. Acta K. Udupa, J. Appl. Electrochem. 1982, 12,
1992, 37, 575. 291.
491. J. Chatt, R. A. Head, G. J. Leigh et al., J. 515. D. Pletcher, M. Razaq, G. D. Smilgin, J.
Chem. Soc., Dalton Trans. 1978, 1638. Appl. Electrochem. 1981, 11, 601.
516. N. E. Gunawardena, D. Pletcher, Acta
492. J. Chatt, W. Hussain, G. J. Leigh et al., J.
Chem. Scand. 1983, B37, 549.
517. M. M. Baizer, (Ed.), Organic Electrochem-
493. P. C. Bevan, J. Chatt, G. J. Leigh et al., J.
istry, Marcel Dekker, New York, 1973.
Organomet. Chem. 1977, 139, C59.
518. M. R. Rifi, N. L. Weinberg, (Eds.), Tech-
494. B. A. L. Crichton, J. R. Dilworth, C. J.
niques of Electroorganic Synthesis Part II,
Pickett et al., J. Chem. Soc., Dalton Trans.
Wiley-Interscience, New York, 1974.
1981, 419.
519. P. N. Anantharaman, H. V. K. Udupa, J.
495. C. J. Pickett, G. J. Leigh, J. Chem. Soc., Electrochem. Soc. 1978, 27, 217.
Chem. Commun. 1981, 1033. 520. M. Noel, P. N. Anantharaman, H. V.
496. K. Unoura, A. Iwashita, E. Itabashi et al., K. Udupa, Electrochim. Acta 1983, 25, 1083.
Bull. Chem. Soc. Jpn. 1984, 57, 597. 521. M. Noel, P. N. Anantharaman, H. V.
497. C. J. Pickett, J. Talarmin, Nature 1985, 317, K. Udupa, Indian J. Technol. 1981, 19, 100.
652. 522. C. Ravichandran, C. J. Kennady, S. Chella-
498. H. M. Colquhoun, A. E. Crease, S. A. Taylor mmal et al., J. Appl. Electrochem. 1991, 21,
et al., J. Chem. Soc., Chem. Commun. 1982, 60.
736. 523. D. Vasudevan, S. Chellammal, P. N. Anan-
499. H. M. Colquhoun, A. E. Crease, S. A. tharaman, J. Appl. Electrochem. 1991, 21,
Taylor, J. Chem. Soc., Chem. Commun. 1983, 839.
1158. 524. C. Ravichandran, D. Vasudevan, P. N.
500. C. J. Pickett, J. E. Tolhurst, A. Copenhaver Anantharaman, J. Appl. Electrochem. 1992,
et al., J. Chem. Soc., Chem. Commun. 1982, 22, 179.
1071. 525. C.-M. Wang, A. Heller, H. Gerischer, J. Am.
501. M. Petit, A. Mortreux, F. Petit, J. Chem. Soc., Chem. Soc. 1992, 114, 5230.
Chem. Commun. 1984, 341. 526. A. Sera, H. Tani, I. Nishiguchi et al., Syn-
502. M. Gilet, A. Mortreux, J. Nicole et al., J. thesis 1987, 631.
Chem. Soc., Chem. Commun. 1979, 521. 527. G. Farnia, G. Sandona, E. Vianello, Elec-
503. M. Gilet, A. Mortreux, J.-C. Folest et al., J. troanal. Chem. Interfacial Electrochem. 1978,
Am. Chem. Soc. 1983, 105, 3876. 88, 147.
504. W. Li, T. Nonaka, Chem. Lett. 1997, 26, 528. R. L. Cook, A. F. Sammells, J. Electrochem.
387. Soc. 1989, 136, 1845.
529. G. N. Petrova, O. N. Efimov, O. A. Tutoch- 555. J. Pinson, J. Armand, Collect. Czech. Chem.
kina, Bull. Acad. Sci. USSR. Div. Chem. Sci. Commun. 1971, 36, 585.
1988, 28. 556. M. R. Rifi, Tetrahedron Lett. 1969, 1043.
530. K. Uneyama, H. Matsuda, S. Torii, Tetrahe- 557. M. R. Rifi, J. Am. Chem. Soc. 1967, 89,
dron Lett. 1984, 25, 6017. 4442.
531. E. G. Gunderson, V. Svetlicic, E. Kariv- 558. J. Casanova, H. R. Rogers, J. Am. Chem. Soc.
Miller, J. Electrochem. Soc. 1993, 140, 1842. 1974, 96, 1942.
532. H. Tanaka, S. Yamashita, T. Hamatani et al., 559. J. Casanova, H. R. Rogers, J. Org. Chem.
Stud. Org. Chem. 1987, 30, 307. 1974, 39, 2408.
533. H. Tanaka, T. Nakahara, H. Dhimane et al., 560. J. Casanova, H. Rogers, J. Murray et al.,
Tetrahedron Lett. 1989, 31, 4161. Croat. Chem. Acta 1990, 63, 225.
534. H. Tanaka, T. Nakahara, H. Dhimane et al., 561. M. S. Mubarak, D. G. Peters, J. Electroanal.
Synlett 1989, 51. Chem. Interfacial Electrochem. 1983, 152,
535. S. Torii, H. Tanaka, M. Satsuki et al., Chem. 183.
Lett. 1981, 10, 1575. 562. M. S. Mubarak, D. G. Peters, J. Org. Chem.
536. M. O. Iwunze, J. F. Rusling, J. Electroanal. 1985, 50, 673.
Chem. Interfacial Electrochem. 1989, 266, 563. M. Tokuda, M. Uchida, Y. Katoh et al.,
197. Chem. Lett. 1990, 19, 461.
537. M. Tokuda, N. Kurono, N. Mimura, Chem. 564. T. Inokuchi, M. Kusumoto, S. Torii, J. Org.
Lett. 1996, 25, 1091. Chem. 1990, 55, 1548.
538. M. Tokuda, Denki Kagaku 1997, 65, 614. 565. D. H. Evans in Encyclopedia of Electro-
539. A. Durant, J. L. Delplancke, V. Libert et al., chemistry of the Elements (Eds.: A. J. Bard,
Eur. J. Org. Chem. 1999, 2845. H. Lund), Marcel Dekker, New York, 1978,
Vol. 12, Chap. 12-1, Organic Section.
540. A. Conan, S. Sibille, J. Périchon, J. Org.
566. E. L. Shapiro, M. J. Gentle, J. Am. Chem.
Chem. 1991, 56, 2018.
Soc. 1979, 101, 5017.
541. K.-H. Schwarz, K. Kleiner, R. Ludwig et al.,
567. T. Inokuchi, T. Sugimoto, M. Kusumoto
J. Org. Chem. 1992, 57, 4013.
et al., Bull. Chem. Soc. Jpn. 1992, 65, 3200.
542. H. Schick, R. Ludwig, K. H. Schwarz et al.,
568. E. Léonard, E. Duñach, J. Périchon, J.
J. Org. Chem. 1994, 59, 3161.
543. M. Tokuda, S. Satoh, H. Suginome, J. Org.
569. H. Hebri, E. Duñach, J. Périchon, Tetrahe-
Chem. 1989, 54, 5608. dron Lett. 1993, 34, 1475.
544. A. Hattori, H. Noda, S. Ikeda et al., Denki 570. H. Hebri, E. Duñach, J. Périchon, J. Chem.
Kagaku 1991, 59, 528. Soc., Chem. Commun. 1993, 499.
545. M. Tokuda, N. Mimura, T. Karasawa et al., 571. H. Hebri, E. Duñach, M. Heintz et al., Syn-
Tetrahedron Lett. 1993, 34, 7607. lett 1991, 901.
546. Y. Rollin, S. Dérien, E. Duñach et al., Tetra- 572. H. Hebri, E. Duñach, J. Périchon, Synth.
hedron 1993, 49, 7723. Commun. 1991, 21, 2377.
547. C. Gosmini, S. Lasry, J. Y. Nédélec et al., 573. B. Espanet, E. Duñach, J. Périchon, Tetra-
Tetrahedron 1998, 54, 1289. hedron Lett. 1992, 33, 2485.
548. J. P. Coleman, J. H. Wagenknecht, J. Elec- 574. H. Schick, R. Ludwig, K. H. Schwarz et al.,
trochem. Soc. 1981, 128, 322. Angew. Chem., Int. Ed. Engl. 1993, 32,
549. K. E. Swenson, D. Zemach, C. Nanjundiah 1191.
et al., J. Org. Chem. 1983, 48, 1777. 575. Y. Ikeda, Nippon Kagaku Kaishi 1990, 1263.
550. E. Kariv-Miller, K. E. Swenson, D. Zemach, 576. Y. Ikeda, E. Manda, Chem. Lett. 1989, 18,
J. Org. Chem. 1983, 48, 4210. 839.
551. E. Kariv-Miller, K. E. Swenson, G. K. Leh- 577. M. Minato, J. Tsuji, Chem. Lett. 1988, 17,
man et al., J. Org. Chem. 1985, 50, 556. 2049.
552. H. Matschiner, R. Voigtlander, H. Schick 578. C.-H. Chen, A. Gewirth, J. Am. Chem. Soc.
et al., Acta Chem. Scand. 1980, B34, 136. 1992, 114, 5439.
553. D. P. J. Hamon, K. R. Richards, Aust. J. 579. H. Tanaka, Y. Kameyama, D. Nonen et al.,
Chem. 1983, 36, 109. Chem. Express 1992, 7, 885.
554. T. Lund, H. Lund, Acta Chem. Scand. 1984, 580. J. H. Choi, J. S. Youm, C. G. Cho et al.,
B38, 387. Tetrahedron Lett. 1998, 39, 4835.
581. K. Sasaki, S. Ito, T. Kinoshita et al., Chem. 586. A. Murata, Y. Hori, Bull. Chem. Soc. Jpn.
Lett. 1983, 12, 445. 1990, 64, 123.
582. R. Tomat, R. Salmaso, S. Zecchin, Elec- 587. H. J. Schäfer, Top. Curr. Chem. 1987, 142,
trochim. Acta 1994, 39, 2475. 102.
583. T. Kinoshita, J. Harada, S. Ito et al., Angew. 588. K. Schnatbaum, H. J. Schäfer, Synthesis
Chem., Int. Ed. Engl. 1983, 22, 502. 1999, 864.
584. Y. Hori, Denki Kagaku 1990, 58, 996. 589. E. M. Belgsir, H. J. Schäfer, Electrochem.
585. Y. Hori, K. Kikuchi, S. Suzuki, Chem. Lett. Commun. 2001, 3, 32.
1985, 14, 1695.
605
16
Conducting Polymers
..
J urgen Heinze
..
Universit at Freiburg, Freiburg, Germany
16.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607
16.2 Mechanism of Electrochemical Polymerization . . . . . . . . . . . . . . . 609

16.2.1 Reactions in Solution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609
16.2.2 Solid-state Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 617
16.3 Redox Processes in Conducting Polymers . . . . . . . . . . . . . . . . . . 625
16.4 Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 636

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 638
607
16.1 materials has gained a new stimulation

Introduction and worldwide many groups are eager to
synthesize specially tailored novel com-
In 1977, the American scientists Heeger, pounds, for example, for the generation of
MacDiarmid, and their Japanese colleague light-emitting materials.
Shirakawa discovered that doping poly- Electrochemistry is one of the most
acetylene (PA) with iodine endowed the promising areas in the research of con-
polymer with metallic properties, includ- ducting polymers. Thus, the method of
ing an increase in conductivity of 10 choice for preparing conducting polymers,
orders of magnitude [1]. The successful with the exception of PA, is the anodic oxi-
doping of PA – the equivalent of oxidation dation of suitable monomeric species such
or reduction in electrochemical termi- as pyrrole [3], thiophene [4], or aniline [5].
nology – encouraged the same scientists Several aspects of electrosynthesis are of
to test PA as a rechargeable active bat- relevance for electrochemists. First, there
tery electrode [2]. Their promising results is the deposition process of the polymers
stimulated worldwide efforts to find ad- at the electrode surface, which involves
ditional applications. In the course of nucleation-and-growth steps [6]. Second,
these studies, conducting polymers with to analyze these phenomena correctly, one
properties similar to PA were discov- has to know the mechanism of electropoly-
ered, such as polyphenylene (PP) and merization [7, 8]. And thirdly, there is the
polyphenylenevinylenes, as pure hydrocar- problem of the optimization of the me-
bons, on the one hand, and polypyrrole chanical, electrical, and optical material
(PPy) polythiophene (PTh), and polyani- properties produced by the special param-
line (PANI) on the other. Nowadays, a eters of electropolymerization.
great number of different monomers that A central point of research is still the
form conducting polymers upon chemical analysis of the electrochemical reaction
or electrochemical preparation techniques occurring during charging, which are also
are known (Fig. 1). known under the term ‘‘doping process’’.
In 2000, Heeger, MacDiarmid, and Shi- Even in the earliest stage of research it was
rakawa were awarded the Nobel Prize clear that these processes were not com-
for their pioneering work in this new parable with the classic doping of typical
field of polymer science. Therefore, it is semiconductors. Rather, they correspond
not surprising that the interest in these to oxidation in the case of p-doping or
608 16 Conducting Polymers
N
n X H
n n n
X = NH, S, O
(1) (2) (3) (4)
R
N
N
H n
n n n
n
(5) (6) (7) (8) (9)
n S S n
n S n
(10) (11) (12) (13)
S
(CH2)n R
N S S n
n
n S n
H
(14) (15) (16) (17)
R R S
O O
S
X X n n X n
X = NH, S S n X = S, O S n
(18) (19) (20) (21) (22)

Fig. 1 Building units of conducting polymers, (1): polyacetylene (PA); (2): polypyrrole
(PPy), polythiophene (PTh), polyfurane (PFu); (3): polyphenylene (PP); (4): polyaniline
(PANI); 5: polyindole (PIND); (6): polycarbazole (PCaz); (7): polyazulene (Paz); (8):
polynaphthalene (PNa); (9): polyanthracene (PAnth); (10): polypyrene (PPyr); (11):
polyfluorene (PFlu); (12): poly(isothionaphthalene) (PITN); (13): poly(dithienothiophene);
(14): poly(thienopyrrole); (15): poly(dithienylbenzene); (16): poly(3-alkylthiophene); (17):
poly(phenylene vinylene); (18): poly(bipyrrole) (PBPy), poly(bithiophene) (PBT); (19):
poly(phenylenesulfide); (20): 4-poly(thienothiophene); (21): poly(thienyl vinylene),
poly(furane vinylene); (22): poly(ethylenedioxythiophene) (PEDOT).
reduction in the case of n-doping. Thus, in to know the phenomenological details of

electrochemical terminology, the doping such redox reactions, for example, in which
process corresponds to a redox reaction. potential range the charging occurs and
Especially for applications, it is important what is the maximum level of oxidation
16.2 Mechanism of Electrochemical Polymerization 609
before the material starts degrading. More- to conducting polymers involves a reaction
over, from the viewpoint of fundamental sequence in which each coupling step has
research, one would like to know the to be activated by two species. It has an
molecular details of the charge storage electrochemical stoichiometry of 2.07 to
process; in recent years, a lot of work has 2.6 farad mol−1 of reacting monomer [7,
gone into explaining this phenomenon [9]. 19]. It has been deduced from numerous
The development of conducting poly- measurements that the film-forming
mers is naturally related to hopes of process needs only 2 farad mol−1 , that is,
feasible technical applications. Thus, con- 2 electrons/molecule, and the additional
ducting polymers are discussed as active charge serves the partial reversible
battery electrodes [10], electrochromic dis- oxidation (doping) of the polymer film.
plays (ECD) [11], anticorrosives [12], sen- As the potential needed for monomeric
sors [13], electrocatalysts [14], antistatic oxidation is always significantly higher
materials [15], or light-emitting materials than the charging of the existing polymer,
(OLED) [16]. the two processes – film formation and its
A basic property of all conducting oxidation – occur simultaneously.
polymers is the conjugation of the chain- Taking this stoichiometry into account,
linked electroactive monomeric units, that the complete reaction equation for the
is, the monomers interact via a π- polymerization of a suitable monomer
electron system. In this respect, they HMH (e.g. pyrrole) is
are fundamentally different from redox
polymers. Although redox polymers also (n + 2)HMH −−−→ HM(M)n MH(nx)+
contain electroactive groups, the polymer + (2n + 2)H+ + (2n + 2 + nx)e−
backbone is not conjugated and the
(1)
interaction between the ‘‘isolated’’ redox
(2n + 2) electrons are used for the poly-
counters is weak. Consequently, redox
merization reaction itself, while the ad-
polymers are nonconductors [17]. They
ditional charging of the polymer film
will not be discussed in this context.
requires nx electrons. In general, x lies
between 0.25 and 0.4. This means that ev-
16.2 ery third to fourth monomeric subunit in
Mechanism of Electrochemical the film is charged.
Polymerization The mechanism of electropolymeriza-
tion is still not fully understood. The one
16.2.1 certainty is that in the very first step the
Reactions in Solution neutral monomer is oxidized to a rad-
ical cation. It must have an oxidation
Electropolymerization of conducting potential that is accessible via a suitable sol-
polymers differs markedly from other vent–electrolyte system and should react
polymerization reactions. In the normal more quickly with identical species than
electrochemically induced polymerization with nucleophiles in the electrolyte solu-
reactions, the electrode catalytically tion. Therefore, as a general rule, polymer-
triggers chain growth and, consequently, ization without defects becomes less suc-
the process requires little electricity [18]. cessful with increasing oxidation potential
By contrast, the anodic oxidation leading of the starting monomer, for example, in
the order pyrrole < thiophene < benzene. easily oxidized than the monomer under
As the nucleophilicity of the solvents com- the given experimental conditions, it is
monly used in electropolymerization rises immediately oxidized to the cation. Chain
in the order HF < CF3 COOH < SO2 < growth should be accompanied by the addi-
CH3 NO2 < CH2 Cl2 < PC < CH3 CN < tion of new cations of the monomeric pyr-
H2 O, only monomers with low oxidation role to the already charged oligomers. This,
potentials such as pyrrole or ethylene- in turn, is followed by another proton elim-
dioxythiophene can be polymerized in ination and the oxidation of the propagated
water [20]. Even in the case of thiophene, oligomeric unit to a cation (Scheme 1).
small amounts of water are sufficient This classic chain-propagation mecha-
for nucleophilic addition to block fur- nism is still widely accepted in the liter-
ther growth of the oligomer chain [21]. ature [23]. However, recent studies using
By contrast, benzene can be only par- the so-called oligomer approach [24] have
tially polymerized in CH3 CN or PC, as shown that this mechanistic view is by
the newly formed oligomers react with the far too simple. Thus, the rate constants
solvent more readily than with the cations of the coupling reactions between the
of the oligomeric intermediates. In dry growing chain and the monomeric cation
SO2 , conductive polyparaphenylene films should not change during the propagation
are formed in high yield [22]. process. However, all experimental data
The very first mechanistic concept for clearly show that the rate constants for
the formation of conducting polymers was the dimerization of monomeric cations
presented by Diaz [7] in 1981. He sug- are high but decrease considerably for
gested, by analogy to the long-known reactions between a chain of increasing
coupling reactions of radical cations in length and monomeric cations. This rules
aromatic compounds, that in the polymer- out a chain-propagation process. Obvi-
ization of pyrrole the monomers dimerize ously, after the formation of a dimer, a
at the α-position after oxidation at the elec- sequence of subsequent ‘‘dimerization’’
trode, and that protons are eliminated from steps leads to the formation of soluble
the doubly charged dihydrodimer, forming oligomers with chain lengths normally
a dimeric neutral species. As the dimer, on ranging between four to eight units [25,
account of its greater conjugation, is more 26]. All these reactions preferably occur in
−2e + + + H −2H+
2 • + • X X
Oxid.
X X X X H + X
Oxid.
n+ (n−1)+
+ −2H+
X + • X X
X X X X X
k k
X = NH, S, O
Scheme 1 Classical formation mechanism of conducting polymers [7].

solution without or with only small pre- 105 M−1 s−1 [30a, 31], that of the pentamer
cipitation on the electrode. Subsequently, is below 104 M−1 s−1 [32].
deposition and growth processes set in, From all these measurements, it is clear
triggered by nucleation reactions. They are that the rate constants of the dimerization
strongly influenced by the concentration of chainlike conjugated oligomers, and
of the starting monomer, the temperature, of their coupling steps with the original
and relevant electrochemical parameters monomer, decrease with increasing chain
such as the formation potential. Espe- length. In addition, the rates of all these
cially, at high concentrations of monomer, second-order reactions are a function
the deposition may begin at a shorter of the concentrations of the reacting
chain length. species. Therefore, as can be shown by
Quantitative investigations of the ki- simulations, a monomeric reactive radical
netics of these α-coupling steps suffered cation as starting species, which is highly
because rate constants were beyond the concentrated, is far more likely to couple
timescale of normal voltammetric experi- with monomeric radical cations than
ments until ultramicroelectrodes and im- with radical cations of higher oligomers
proved electrochemical equipment made (Scheme 2).
possible a new transient method called fast Studies by Heinze et al. on donor-
scan voltammetry [27]. With this technique, substituted thiophenes or pyrroles [33]
cyclic voltammetric experiments up to scan such as methylthio (= methylsulfonyl)
rates of 1 MV s−1 are possible, and species or methoxy-substituted derivatives provide
with lifetimes in the nanosecond scale further clear evidence for this reaction
can be observed. Using this technique, pathway. They found, for instance, that
P. Hapiot et al. [28] were the first to obtain 3-methylthiothiophene or 3-methoxythio-
data on the lifetimes of the electrogener- phene (2) undergo a fast coupling reaction.
ated pyrrole radical cation and substituted However, deposition processes or insolu-
derivatives. The resulting rate constants ble film formation could not be detected
for the dimerization of such monomers in usual experiments with these com-
lie in the order of 109 M−1 s−1 . The same pounds, even at high concentrations. Sim-
authors were also able to show that the ilarly, the corresponding 3,3 -disubstituted
radical cation of the pyrrole tetramer, by bithiophenes (2a) do not polymerize, but
contrast, is rather stable [28c]. The data the anodic oxidation of 4,4 -disubstituted
indicated that the rate constant of dimer- bithiophenes (2c) produces excellent yields
ization is lower than 104 M−1 s−1 . This of conducting polymers.
tendency of decreasing reactivity as a func- A careful analysis based on these
tion of chain length is a general property experimental results excluded a chain-
of all chainlike conjugated oligomers [29]. propagation process [33a]. On account
Thus, in the series of unsubstituted thio- of the 3-position of the methylthio or
phenes, the radical cations of monomeric methoxy substituent in the thiophene
thiophene dimerize with a rate constant or pyrrole rings, three isomeric dimers
greater than 109 M−1 s−1 , while the life- may be formed. The main reaction path
times of oligomer cation radicals increase can be deduced from the mesomeric
with chain length [30]. For example, the forms of the radical cations (2)+• . The
rate constant for the dimerization of the two most important mesomeric structures
unsubstituted thiophene tetramer is about are those with the unpaired electron in
−2e + + + H −2H+
2 • + • X X
X E 01 X X kf ≈ 109 X X
H +
−2e H +
2 X 2 X X X
X E 02 X • kf ≈ 108 X X
+ + H
kf < 10 −2H+
2 X X
X X X X
E 30
n=2 n=2
−2e
+ 2,2′
2 X • X + H X X
X X kf ≤ 104 X X X
H +
n=2 n=2
n=2
3,3′
X X
+ X
H
n=2
H
X +
X X
n=2
+ H −2H+
e.g. X X X 2 X
X X X kf ≤ 1 X X
H +
n=2 n=6
n=2
X = NH, S, O E10 > E 02 > E 03
Deposition
Scheme 2 ‘‘Dimerization’’ steps during oligomerization in solution as deduced from the

oligomer approach.
an α-position (I, II). Structure I, with The main products initially formed,
the positive charge next to the donor dimers (2a), will undergo further slow
substituent, is preferred, because of the coupling steps. At the given potentials,
stabilizing +M-effect of the methoxy or dimers (2a) will immediately be oxi-
methylthio substituents. Therefore, the dized to the corresponding monoradical
3,3 -disubstituted- 2,2 -dimers (2a) are the cations. Again, the monoradical cations
essential products of the radical–radical can be found in different mesomeric
coupling process. Dimers (2b) and (2c) are structures. The most reasonable notation
minor side products (Scheme 3). has the positive charge next to the donor
Fast
R R
+ *2 X Slow
• 2a
−2H+
X X
I TMS
R R
−e−
−2H+
X
+e− 2b
X X
(2) R
R R
*2 X
+ • Fast
−2H+ 2c
X X
II Slow R
R = −OCH3
−SCH3
X = S, NH
Scheme 3 First coupling steps after the oxidation of 3-methylthio- or 3-methoxythiophene
(pyrrole) (2).
substituent and the unpaired electron at the oxidation of 3-methoxythiophene (2)

the blocked inner α-position as shown be- and 3,3 -dimethoxybithiophene (2a) are
low in the important mesomeric structures identified as a tetrathiophene derivative.
of the radical cations of (2a). By contrast, the high polymerization
tendency of dimers (2c) is a result of the
+ fact that the most important mesomeric
ZCH3 ZCH3
+
structures (see below) have the unpaired
• X • X electron at a nonblocked site. The coupling
X X of the radicals is very fast, and the
CH3Z CH3Z products of the coupling steps in turn have
X = S, NH (2a) Z = O, S
substituents in ‘‘outer’’ β-positions of the
oligomer, which makes it reactive [33].
Therefore, the reactivity of these +

cationic species, similar to that of all CH3Z CH3Z
other 3,3 substituted bithiophenes or •
+
X • X
bipyrroles, is low, probably resulting in X X
a rate constant for the dimerization ZCH3 ZCH3
of ≤ 104 M−1 s−1 [33d]. The tetrameric X = S, NH (2c) Z = O, S
products of the subsequent coupling are
even more stable than the dimers, which
means that the ‘‘polymerization’’ process All these findings prove that the
stops at this level, or becomes very electropolymerization mechanism of
slow. This reaction pattern is shown in donor-substituted thiophenes and pyrroles
Fig. 2, where the resulting species of does not involve a chain-propagation
OCH3
S OCH3
S
H3CO S
Normalized i
−2 −1 0 1 2
E (vs Ag/AgCl)
[V]
Fig. 2 Cyclic voltammetry for the oxidation of 3-methoxythiophene (2), c = 6 ∗ 10−4 in

acetonitrile + 0.1 M TBAPF6 , v = 0.1 V s−1 and 3,3 -dimethoxy-bithiophene (2a),
v = 0.1 V s−1 . The resulting oligomer after the oxidation of both (2) and (2a) is a
tetrathiophene derivative, which can be reversibly oxidized up to a dication (see square).
process with successive coupling steps of such as homogeneous symproportion-

the starting radical cation. By contrast, it ations (D2+ + M− −
−−−
−M+• + D+• ) auto-
must be concluded that oligomerization in catalytically produce radical cations of
solution preferably occurs via consecutive the lower oligomers [34]. Other possi-
‘‘dimerization’’ steps leading from a dimer ble side reactions are, for example, (re-
to a tetramer and then to an octamer. In versible) dimerization without elimina-
the case of a hypothetical chain growth tion of protons or β-linkage reactions.
reaction, the extremely high reactivity of Thus, Cava et al. could show that during
(2)+• should trigger an almost perfect oligomerization in solution branched
formation of a polymeric chain. However, β –β-coupling steps compete with the lin-
this has never been observed. ear α –α-coupling [35]. In addition, their
It would be an oversimplification to results reveal that the elimination of
assume that these simple coupling and protons after the coupling of the radi-
electron-transfer reactions reflect all the cal cations may be slow. In this case,
steps occurring in front of the elec- a charged σ -complex exists as a short-
trode. In addition, parallel reactions lived intermediate. In the case of the
pyrrole oligomerization (dimer–tetramer), length. An important consequence of this

the deprotonation step is significantly behavior is that oligomeric chains cannot
slower than the radical–radical coupling grow via the coupling of a monomeric
step [28d], indicating that the stability of species with an oligomeric chain because
the σ -dimer increases as a function of the resulting intermediates do not elimi-
chain length. nate protons.
The importance of the proton elimi- An essential prerequisite for successful
nation has been overlooked for a long oligomerization and polymerization is a
time. Originally, it was assumed that sufficiently ‘‘strong’’ base in solution to ac-
proton elimination is always a fast cept the protons from the σ -intermediates.
reaction the driving force of which In the case of protonated pyrroles, the
is the rearomatization of the system pKa value lies in the range between 4
and that rate-determining steps during and −4, whereas the pKa value of ace-
electropolymerization are related to cou- tonitrile is about −10. Therefore, the
pling reactions between cationic species. oligomerization of pyrrole in pure ace-
The new findings clarify details of the poly- tonitrile may already stop at the level of
merization reaction, which have not been σ -intermediates of bi- or more likely of
understood up to now. Obviously, the rates tetrapyrrole. Acetonitrile is a weaker base
of proton elimination from ‘‘dimeric’’ cou-
than the σ -intermediates. Consequently,
pling intermediates diminish so drastically
a stronger base must be used to initiate
that charged σ -dimers with more than four
the elimination of protons. Water fulfills
units in one conjugated chain segment are
this condition. Pyrrole can be polymer-
fairly stable in the charged state. Proton
ized in acetonitrile in the presence of 1%
elimination from such species takes place
water [6, 37]. A similar effect results from
only when σ -intermediates are oxidized to
the application of a sterically hindered base
a higher charging level, which increases
such as 2,6-di-tert-butylpyridine [38]. How-
the reactivity of the system. Thus, the
charged σ -dimer of the thiophene octamer ever, the concentration should be kept low
does not undergo a deprotonation step as because, at high concentrations proton,
long as the electrode potential does not abstraction from the monomeric radical
exceed the oxidation potential of the oc- cation may occur, thus forming a neu-
tathiophene trication [36]. The reason for tral radical [28d]. The ‘‘base’’ effect can be
this effect is that the acidity of proton con- also observed in the case of thiophenes.
taining coupled σ -intermediates decreases For example, the rate of oligomerization
as a function of chain length and the num- and polymerization increases when 2,6-
ber of electron-donating groups within the di-tert-butylpyridine is added to a solution
oligomer. The positive charges are stabi- of bithiophene. However, in the case of
lized in dependence on electronic factors monomeric thiophene, the high oxidation
and the extent of the conjugated system. potential of the starting species between
Thus, ‘‘σ -dimers’’ of pyrrole oligomers are (>1.6 V versus Ag/AgCl) prevents any for-
more stable than the corresponding thio- mation of conducting polymeric material.
phene oligomers; and the chain length cri- The reason is that under these condi-
terion proves greater stability – that means tions nucleophilic substitution reactions
a lower tendency for proton release – of between the respective base and the highly
such intermediates for an increasing chain reactive cations take place or the formation
of neutral radicals leads to unknown side of these species takes place between the
products [21, 28d, 39]. radical cations (RR coupling). It is also
Recently, the discussion about the for- noteworthy that the dimerization step is,
mation of π- or σ -dimers as intermediates in principle, chemically reversible. After
of the oligomerization has intensified. the reduction of the dimer, the starting
Thus, on the basis of concentration and species is regenerated. Moreover, no pro-
temperature-dependent UV–vis and ESR tons are eliminated from the dicationic
data, Miller et al. have suggested that the dimer. Owing to the electron-donating
radical cations of substituted oligothio- amino nitrogens, the acidity of the dimer
phenes may form π-dimers [40]. Other is so weak that rearomatization from the
authors have subsequently reached similar dicationic σ -dimer to the neutral biphenyl
conclusions [41]. In all cases, voltammetric cannot take place and can be achieved only
analysis indicates the reversible forma- after the addition of a strong base. A similar
tion of radical cations without chemical tendency can be observed in the formation
follow-up steps. Accordingly, it has been of conducting oligomers and polymers.
concluded that weakly interacting π-mers The stability of the ‘‘σ -dimers’’ increases
form rapidly and also decay relatively with the length of the growing chain.
quickly in the experimental timescale. In the past, some authors [46] have
Very recent cyclic voltammetric stud- questioned the radical–radical coupling
ies of the oxidation of diphenylpolyenes, (RR) mechanism on the ground that the
oligophenylenevinylenes, and oligothio- strong coulomb repulsion between small
phenes have indicated strong changes cation radicals renders a direct dimeriza-
of the voltammetric response as a function of such particles improbable. Instead,
tion of temperature, concentration, and they postulated a radical–substrate cou-
scan rate. A detailed evaluation of all pling (RS). An electrophilic attack by the
data gave clear evidence that the for- radical cation on the neutral monomer
mation of the radical ions is followed or oligomer produces the single-charged
by rapid reversible dimerization between coupling product, which eliminates its
oligomer chains, accompanied by the protons only after a further charge trans-
formation of a σ -bond [42]. Moreover, fer, becoming a neutral oligomer. How-
applying NMR measurements, A. Merz ever, the principal objection to the RR
et al. could show that the radical cations path – the strong Coulombic repulsion
of 5,5 diphenyl-3,3 ,4,4 -tetramethoxy-2,2 - between charged particles – is not con-
bipyrrole reversibly dimerize and form vincing for reactions in solution. Using
a σ -dimer in solution, the equilib- the Debye–Smoluchovski theory [47], it
rium constant of which is temperature- has been shown that even small ionic
dependent [43]. Similarly, by oxidizing molecules that are equally charged are
1,3,5 tripyrrolidinobenzene, Effenberger able to dimerize at a diffusion-controlled
et al. succeeded in isolating a dimeric rate [48]. Recently, applying the oligomer
σ -complex and, by using X-ray structure approach, several authors have demon-
analysis, were able to unequivocally prove strated that the ‘‘dimerization’’ reactions
the existence of the σ -bond in the of heterocyclic monomers and oligomers
solid state [44]. Using cyclic voltamme- involve coupling between two electrogen-
try and spectroscopic techniques, Heinze erated cation radicals rather than with the
et al. [45] could show that the dimerization starting molecule [28, 32, 33, 42, 43, 45].
Careful quantitative kinetic studies of the the typical t −1/2 drop. In potentiodynamic
coupling steps of oligomeric pyrroles and experiments, the observed oxidation cur-
thiophenes have confirmed this mecha- rents, as well as the visible changes on
nistic pattern [49]. In addition, quantum the electrode surface, are dependent on
chemical studies reveal that the dimer- the scan rate. The slower the scan rate,
ization of two radical cations becomes the more visible the electrode coating and
perfectly feasible when solvent effects are the greater the rise in the oxidation cur-
included [50]. rent [56]. The electrodeposition process
can be also monitored by spectroelectro-
16.2.2 chemical in situ techniques [57]. Especially
Solid-state Processes useful are ellipsometric studies [58] com-
bined with time-resolved UV–vis spec-
Despite the vast quantity of data on troscopy [59, 60]. Measurements of the
electropolymerization, relatively little is deposition of oligothiophenes reveal that
known about the processes involved in the during the starting period of electrolysis
deposition of oligomers (polymers) on the only species in the solution phase are
electrode, that is, the heterogeneous phase generated and that the growth of the nu-
transition. Research – voltammetric, po- clei is not a simple three-dimensional
tential, and current step experiments – has deposition process but a fairly com-
concentrated largely on the induction stage plex one.
of film formation of PPy [6, 51], PTh [21, The literature contains descriptions of
52], and PANI [53]. In all these studies, trace-crossings or nucleation loops that
it has been overlooked that electropoly- normally appear on the reverse sweeps
merization is not comparable with the of the first cycle in all voltammograms,
electrocrystallization of inorganic metal- provided the scan reversal lies close to
lic phases and oxide films [54]. Thus, two- the peak potential [51a]. This has been in-
or three-dimensional growth mechanisms terpreted as the start of the nucleation
have been postulated on the basis that process of the corresponding polymer.
the initial deposition steps involve one- or A strong argument for this assumption
two-electron transfers of a soluted species has been that this effect always appears
and the subsequent formation of ad- in voltammetric experiments with freshly
molecules at the electrode surface, which polished electrodes and only in the re-
may form clusters and nuclei through verse sweep of the first cycle [6, 51,
surface diffusion. These phenomena are 61]. Such behavior is similar in this re-
still unresolved. spect to the electrochemical deposition of
Electropolymerization begins with the metal on a foreign substrate, in which
formation of oligomers in solution. Above an overpotential is required for nucle-
a critical chain length, insoluble oligomers ation, after which further growth of the
form, which deposit themselves on the metallic layer occurs at the characteristic
electrode surface [55]. Two additional redox potential of the metal, leading to a
findings support this thesis. In potential trace-crossing in the reverse sweep. How-
step experiments, optical signals indicat- ever, recent voltammetric studies have
ing the deposition of oligomers on the shown that such trace-crossings still ap-
electrode only change when the current pear even if deposition processes or in-
on the i–t curve starts to rise again after soluble film formation cannot be detected
under any conditions, even at high con- radical cations such as pyrrole or thio-
centrations [33a]. Moreover, the potentio- phene (see Scheme 2, Eqs. 2–7).
dynamic electropolymerization of pyrrole
or substituted derivatives at high concen- −e
M slow M+• (2)
trations produces the trace-crossing, even
after the electrode has become polymer- 2M+• [DimH2]2+ (3)
coated [62]. This is inconsistent with an
Base
interpretation based on the nucleation- [DimH2]2+ Dim (4)
−2H+
and-growth mechanism. Normally, during
−e
multisweep experiments trace-crossing Dim Dim•+ (5)
disappears because of the fact that the
−e
growing polymer layer produces a sig- Dim•+ Dim2+ (6)
nificant cathodic current in the reverse
voltammetric sweep. +
By contrast, experimental data support Dim2+ + M Dim•+ + M• (7)
the view that the additional anodic cur-
Symproportionation reactions occur be-
rent observed in the reverse sweep results
tween dications of the dimer and the
from slow follow-up or symproportiona-
neutral monomeric starting species. Al-
tion reactions occurring in the diffusion
though the thermodynamic equilibrium
layer in front of the electrode. In the early
lies on the left side, the fast coupling re-
1970s, Feldberg [63] demonstrated the the-
action of M+• shifts the reaction to the
oretical possibility of trace-crossing in ECE
right side and generates an additional
reactions (electrochemical, chemical, elec-
flux of oxidizable species which results
trochemical) involving slow rate constants
in a strong trace-crossing (Fig. 3). Simu-
for the chemical step. This is one process
lations which have been carried out for a
that may take place during the oligomeriza- vast number of different rate parameters
tion of the monomeric starting species in and mechanistic variants show that both
solution. Trace-crossing results from the symproportionation reactions and slow
slow formation of a neutral tetramer or oc- eliminations of protons from the dihy-
tamer (k ≈ 104 M−1 s−1 ) in the diffusion drodimer explain the trace-crossing [33a,
layer and its subsequent oxidation to its 64, 65]. Up to now, all available results
mono- or dication. The rate-determining indicate that the so-called nucleation loop
step is the slow elimination of protons in cyclic voltammetry is not the result of
from charged σ -intermediates. a nucleation step but of homogeneous
The fact that extensive trace-crossing is follow-up reactions of soluble oligomers
also observed during generation and depo- in the diffusion layer.
sition of oligomers has stimulated further Galvanostatic, potentiostatic, or poten-
explanations [64]. A very realistic mecha- tiodynamic techniques can be used to elec-
nism that is in excellent agreement with tropolymerize suitable monomeric species
experimental data is based on the assump- and form the corresponding film on
tion of homogeneous symproportionation the electrode. The potentiodynamic ex-
reactions (Eq. 7) taking place after the periment, in particular, provides useful
generation and oxidation of dimers that information on the growth rate of conduct-
are formed by the coupling of monomeric ing polymers. The increase in current with
40
CH3O OCH3
N
CH2
20
[µA]
I
−0.6 0.0 0.6

E (vs Ag/AgCl)
[V]
Fig. 3 Multisweep cyclic voltammogram (6 scans): trace-crossing effect during
potentiodynamic polymerization of N-benzyl-3,4-dimethoxy-pyrrole in acetonitrile, 0.1 M
TBAPF6 , +1% H2 O, v = 200 mV s−1 , T = 298 K.
each cycle of a multisweep cyclic voltam- the monomer and short oligomers are ox-
mogram (CV) is a direct measure of the idized (Fig. 5). In general, no deposition
increase in the surface of the redoxactive is observed outside of this range. Surpris-
polymer and, hence, a measure of relative ingly, lowering the temperature raises the
growth rates (Fig. 4). efficiency of deposition owing to the fact
The relative growth rate per cycle v is that the solubility of the soluble oligomers
calculated from the anodic peak current decreases [66].
of the respective polymer oxidation using However, despite all these observations,
Eq. (8) it is still unclear which additional coupling
pol steps take place after the nucleation of
k · ipa an oligomeric layer on the electrode. In
v= (8)
(n − 1) the literature, experimental data have been
presented to support the view that, with
where k is a proportionality constant. The the formation of an oxidized ‘‘prefilm’’,
parameter v is by its nature a function of the process gradually transforms into
the conditions of polymerization and, thus, one in which the chain growth can
must be standardized to v0 , in relation to take place on the surface immediately
which only one growth parameter may be by coupling of the monomer cation
changed [38]. Quartz microbalance mea- radical and the oxidized chain in the
surements reveal that deposition occurs film [67]. However, the assumption of
preferably in the potential range where heterogeneous coupling of monomers
Fig. 4 Potentiodynamic growth of a

E Mon polypyrrole film in acetonitrile (+1%
15. Cycle
pa
H2 O), v = 0.1 V s−1 , T = 298 K,
E pol
pa
number of cycles n = 15, Epamon = 1.0 V
pol
versus Ag/AgCl, Epa = 0.31 V
versus Ag/AgCl.
i Pol
pa
1. Cycle
8 µA
−1.2 −0.8 −0.4 0.0 0.4 0.8 1.2

E (vs Ag/AgCl)
[V]
or dimers with the existing layer of for instance, allows the reversible genera-
oligomers seems rather improbable, as tion of trications or even tetracations. This
the oligomers in the film are not highly stability disappears when the temperature
reactive and the rate constants for the is raised. If, in the case of H-T8 -H, the
dimerization of monomers or dimers are switching potential is set in the ascent of
very high. the anodic trication wave at 1.25 V, two
A few years ago, solid-state voltammet- new waves appear – one in the anodic,
ric measurements on sexiphenylene layers the second one in the cathodic scan – and
revealed for the first time that the material gradually increase, while the original sig-
‘‘polymerizes’’ upon p-doping in the solid nals for redox processes of the starting
state on the electrode [68]. It was shown material decrease (Fig. 6).
that sexiphenylene dimerizes at low oxi- The resulting isopotential point con-
dation potentials, while at high potentials firms that H-T8 -H reacts to produce a
long chains are produced and cross-linking new electroactive species without side re-
steps become more and more predomi- actions. The optical absorption of the
nant [69]. Since then, further solid-state electrochemically generated product is red-
experiments with monodisperse oligothio- shifted and its cathodic peak potentials
phenes have confirmed these early results upon discharging (reduction) lie negative
and provided new insights into the general to those of the educt, indicating that the
polymerization mechanism of conducting product consists of larger molecules with
polymers [36]. a more extended redox system. If exper-
The application of low-temperature iments are carried out at higher sweep
voltammetry to octathiophene (H-T8 -H), rates (v > 100 m V s−1 ), broad waves are
200
150
100
[µA]
I
50
−50
−1.0 −0.5 0.0 0.5 1.0

E (vs Ag/AgCl)
(a) [V]
−1000
Frequency
[Hz]
−2000
−3000
−4000
−1.0 −0.5 0.0 0.5 1.0

E (vs Ag/AgCl)
(b) [V]
−1000
Frequency
[Hz]
−2000
−3000
−4000
0 2 4 6 8 10 12
Charge
(c) [mC]
Fig. 5 Quartz crystal microbalance measurements during potentiodynamic
polymerization of 4,4 -dimethoxy-bithiophene in CH2 Cl2 , 0.1 M TBAPF6 ,
v = 0.01 V s−1 : (a) cyclic voltammetry; (b) frequency-potential plot showing
mass changes as a function of the applied potential; (c) frequency charge plot
showing mass changes as a function of charge consumed during
potentiodynamic cycling.
Fig. 6 Potentiodynamically generated

solid-state coupling of octathiophene:
(a) cyclic voltammogram of H-T8 -H,
Eλ = 1.07 V; (b) cyclic voltammetry
during coupling, Eλ = 1.25 V; (c) cyclic
voltammogram of H-T16 -H,
Eλ = 1.25 V. The resulting
sexidecithiophene forms a stable
σ -‘‘dimer’’ after oxidation. Experimental
conditions: CH2 Cl2 /TBAPF6 , T = 268 K.
(a) [From Ref. [36].]
short-chain oligomers, such as sexithio-

phene or sexideciphenylene, leading to
dodecathiophene and -phenylene. All these
materials can be polymerized further at
higher formation potentials. The num-
(b)
ber of coupling steps depends strongly
on the applied potential. At the end of
(c) such processes, the voltammograms have
0.0 0.5 1.0 the typical shape of those of conducting
E (vs Ag/AgCl) polymers in general, that is, they exhibit
[V] the characteristic current plateau and high
current waves at different potentials at the
onset of charging and the end of discharg-
observed during the cathodic reverse scan ing. Under these conditions, the average
at potentials around 0 V. This is typical functionality may be larger than the lim-
for the discharging of protons formed dur- iting value for infinite chains (f = 2).
ing the process. The coulometric analysis From this, however, it must be concluded
of the voltammograms shows that one that chain-lengthening steps as well as
charge is lost per molecule (by proton coupling reactions between the chains
cleavage) in the condensation reaction. take place, leading to a network with σ -
The average functionality of a monomer interchain bonds (sp3 –sp3 ) and regular
unit, f , has been calculated from coulo- bonds between sp2 –sp2 centers. All these
metric data. The resulting values of f < experiments give no indication of a poly-
2, together with all other observations, mer of infinite length. On the basis of IR
give clear evidence that the short-chain data, Furukawa et al. concluded from stud-
H-T8 -H dimerizes quantitatively in this ies of thiophene oxidation that the degree
solid-state reaction, forming an isomer of of polymerization is rather low, ranging
sexidecithiophene. This product may be from 10 to 35 [70]. For the conjugation
α, α -, α, β -, or β, β - coupled. In any length of PTh, a number of ca. 11 has been
case, the hysteresis between the charg- estimated [71].
ing and discharging steps is characteristic In very recent publications, it was shown
of the formation of σ -intermediates dur- that the quality of the polymerization
ing the polymerization process. Analogous process and the structure of the result-
reactions have been observed for other ing polymers strongly depend on the
formation potential applied during the formation of PPy (III). In highly acidic
electrochemical experiments [26, 37, 62, solutions at low formation potentials, a
72]. Thus, in the case of polypyrrole, two passivating film is generated (PPy (IV)).
variants showing well-shaped voltammo- PPy was the first conducting polymer
grams can be clearly distinguished. PPy to be structurally analyzed. The discovery
(I), which is the dominant component that α, α -disubstituted pyrrole did not
of polypyrrole, normally prepared under polymerize led to the conclusion that the
mild conditions at a formation potential
of 0.9 V versus Ag/AgCl, has an oxida-
tion wave at 0.0 V and a reduction wave
at −0.28 V. (Fig. 7) It turned out that the
material obtained is weakly cross-linked
and contains σ -interchain bonds and reg-
ular bonds between the chains. PPy (II)
which is generated at very low forma-
tion potentials of +0.75 V or less has a PPy (I)
sharper wave at ca. −0.23 V and a fairly
broad much weaker reduction wave at
−0.37 V. PPy (II) is a material which con-
tains linear chain sequences with eight
units and is cross-linked via σ -bonds. This
establishes unconventional properties of
the polymers such as a cation exchange
mechanism during charging and discharg-
ing. A third variant is PPy (III). It is a
partially conjugated polymer with both sat-
urated pyrrolidine and unsaturated rings
PPy (II)
in a polymeric network. The acid cat-
alyzed trimerization of pyrrole and the
follow-up electrochemical and chemical
reactions [73] play a crucial role in the
Fig. 7 PPy variants generated by

galvanostatic or potentiodynamic
techniques. PPy (I) is formed in
acetonitrile with 1% water. The average
conjugation length is about 30 units. PPy (III)
The material is weakly cross-linked. PPy
(II) is formed at low oxidation potentials
(≤0.75 V versus Ag/AgCl)or low current
densities (6 µA cm−2 ). It consists of
short chains with σ -dimers in the
charged state. PPy (III) showing
symmetric voltammograms during
charging and discharging cycles is a −1.2 −0.8 −0.4 0.0 0.4 0.8 1.2
strongly cross-linked material. [From E (vs Ag/AgCl)
Ref. [73].] [V]
pyrrole units in PPy are α-linked [74]. suitable for characterizing structural prop-
Magic angle spinning 13 C-NMR data erties. These comprise surface techniques,
supported the view that the pyrrole units such as XPS, AES (Auger electron spec-
are linked chiefly in the α, α -position, troscopy), or ATR (attenuated total re-
although α, β bondings are also found [75]. flection [IR] spectroscopy), on the one
On the other hand, already in 1984, XPS hand, and the usual methods of structural
measurements of PPy revealed that a full analysis, such as NMR, ESR, and X-ray
one-third of the pyrrole rings in a chain diffraction techniques, on the other [79].
are irregularly bonded [76]. During the 1980s, the chain length
Similarly, a chain structure with pre- criterion was the most important factor
dominantly α, α -coupling between the related to the structural characterization
monomer units was postulated for poly- of conducting polymers. The importance
thiophene (PTh) on the basis of spectro- of this parameter lies in the consider-
scopic findings and mechanistic studies. able influence of the electric as well as
IR measurements of uncharged, chem- the electrochemical properties of conduct-
ically produced examples, in particular, ing polymers. However, the molecular
clearly revealed that α, α -bonding pre- weight techniques normally used in poly-
dominated in the polymers produced from mer chemistry cannot be employed on
α, α -dibromothiophene, 2,2’-bithiophene,
account of extreme insolubility of the
or 3-methylthiophene [4, 77]. The IR
materials. A comparison between spec-
data correlated very well with 13 C-NMR
troscopic findings (XPS, UPS, EES) for
measurements, which similarly confirm
PPy and model calculations has led some
the dominance of α, α -bonding in P3-
researchers to conclude that 10 is the
MeTh [78]. In agreement with these find-
minimum number of monomeric units
ings, the electrochemical oxidation of
in a PPy chain, with the maximum
3,3 ;5,5 -tetramethyl-2,2 -bithiophene un-
within one order of magnitude higher [76,
ambiguously demonstrated that the non-
blocked outer β-position is nonreac- 80]. By electropolymerizing α, α -tritium
tive [42c]. However, it should be noted labeled β, β -dimethylpyrrole and compar-
that the coupling steps of thiophene ing the tritium activity in the monomer
oligomers may involve interchain re- and the polymer, Nazzal and Street ob-
actions leading to a polymeric net- tained molecular weights which indicate
work. The reactivity of such oligomers chain lengths of between 100 and 1000
depends on their respective charging pyrrole units [81]. By contrast, the oligomer
level. approach has shown that oligomerization
All these data show that only small in solution produces soluble oligomers
changes of the polymerization parame- with chain lengths between 8 to 12
ters may lead to characteristic differences units. During solid-state polymerization
in the resulting structures of conduct- in dependence on the applied electrode
ing polymers. Structural properties – for potential, linear chains up to 30 units
example, regularity and homogeneity of as well as cross-linked networks are
chain structures, but also chain length play generated [25, 69]. Thus, the real chain
an important role in our understanding of length is still unclear but cross-linking ef-
the properties of such materials. Spectro- fects may contribute to high molecular
scopic methods have proved particularly weights.
16.3 Redox Processes in Conducting Polymers 625
16.3 with identical peak potentials and current

Redox Processes in Conducting Polymers levels (Fig. 8).
The current in the reversible case is then
Conducting polymers, provided they are
chemically produced, are initially insula- n2 F 2 AT v · exp
i= , (9)
tors. Their metallike properties, that is, RT (1 + exp )2
their high conductivity and optic reflectiv-
where = (nF /RT )(E − E 0 ), and T =
ity, only become obvious after ‘‘doping’’.
0 + R correspond to the total surface
Even in the earliest stages of research on
covered with reduced and oxidized sites.
these materials, it was clear that these
The other parameters have their usual
processes were not comparable with the
meanings. Apart from the mirror sym-
classic doping of inorganic semiconduc-
metry of the waves, it is also characteristic
tors. Rather, they correspond to oxidation
that, in contrast to measurements obtained
in the case of p-doping or reduction in the
with soluble redox systems, current i and
case of n-doping. Suitable redox reagents
the scan rate v are directly proportional to
are either chemical electron acceptors,
each other.
such as iodine, or electron donors, such
The above statements are valid for
as potassium naphthalide; or the process
monomolecular layers only. In the case
may be electrochemically induced via an
of polymer films with layer thickness
electrochemical cell. Because of the redox
into the µ-range, as are usually pro-
reaction, the polymer chain is negatively
duced by electropolymerization, it must
charged in the case of reduction and posi-
be taken into account that charge trans-
tively charged in the case of oxidation. To
port is dependent on both the electron
maintain electroneutrality, the appropriate
exchange reactions between neighboring
counterions diffuse into the polymer dur-
oxidized and reduced sites and the flux of
ing charging and out of the polymer during
counterions in keeping with the principle
discharging.
of electroneutrality [84, 85]. Although the
The knowledge that conducting poly-
mers can be charged, that is, oxidized and
reduced, raised the question of possible
Ep = E 0
applications, such as the construction of a
polymer battery, at an early stage [82]. But i
basic research was long unable to explain
the charge storage mechanism. Theoreti- ip
cal concepts that describe the voltammetric
response during charging and discharging
of redoxactive films were developed more
than two decades ago [83]. In the ideal case,
reversible cyclic voltammograms (CVs)
should show completely symmetrical and
mirror-image cathodic and anodic waves
−0.2 0.0 0.2

Fig. 8 Theoretical cyclic
voltammogram for a redoxactive film (E − E 0)
with noninteracting sites. [V]
molecular mechanisms of these processes when polymeric films are produced under
are not yet understood in all their detail, mild conditions at low formation poten-
their phenomenology can be adequately tials [4, 5, 11c, 19, 34, 74]. Characteristic
described by the laws of diffusion. All vari- features of these systems are, in the case
ants of the diffusion mass transport are of the p-doping, a steep anodic wave at
possible from the finite limiting case to the start of charging, followed by a broad
semi-infinite diffusion, depending on film flat plateau as potential increases. In the
thickness, the values of the formal dif- reverse scan, a potential-shifted cathodic
fusion coefficients, and the experimental wave appears at the negative end of the
timescales used. For voltammetric experi- capacity-like plateau.
ments, this implies that as the sweep rate The conspicuous separation between the
increases there must be a shift from mirror cathodic and anodic peak potentials (hys-
symmetrical CV diagrams with i propor- teresis) was initially interpreted in terms
tional to v to the classic, asymmetrical of the simple theory of redox polymers
voltammograms with i proportional v 1/2 . as a kinetic effect of slow heterogeneous
Although the potentiodynamic charging charge transfer; the thermodynamic redox
and discharging of conducting polymers potential of the whole system was calcu-
produces voltammograms of very different lated from the mean value between Epa
shape depending on type and polymer- and Epc [5, 7a, 86]. As a simplification,
ization conditions, one frequently finds it was assumed that the interaction be-
CV diagrams (Figs. 7, 9) with a very sim- tween the charged oligomeric segments
ilar shape. This is particularly the case was negligible. These redox data correlate
Epa
PPy
E0
Epc
−1.0 −0.5 0.0 0.5 1.0 1.5

E (vs Ag/AgCl)
[V]
Fig. 9 Cyclic voltammogram for the oxidation of polypyrrole,
v = 0.5 mV s−1 , T = 298 K.
well with potential values obtained by resistivity is inversely related to the amount
extrapolation from quantum mechanical of (oxidizing) charge [93]. In a neutral poly-
calculations [87] and redox potential mea- mer, the initial resistivity may be large
surements [29, 88, 89] on oligomers of enough to produce a significant iR drop
defined chain length. As expected, with in- thereby delaying the onset of oxidation. A
creasing conjugation length, the respective small amount of oxidation can cause a re-
oxidation and reduction potentials shift to- duction in resistivity and the charge will
wards lower energy values. However, the flow at some later stages of the scan.
small discrepancy between the measured Another concept has been developed
and the extrapolated Epa values gave rise on a refined model based on two-step
to the opinion that the conjugation length redox systems typical for organic com-
of the neutral polymer covered only 5 to 10 pounds [94]. This concept treats a polymer
monomeric units [88]. chain with the degree of polymerization
Furthermore, from quantum mechan- n as x weakly interacting segments con-
ical findings, it was concluded that the taining k monomeric units, each of which
onset potentials measured in the poly- can be charged up to a diionic state in
mers reflected only the initial ionization of two redox steps with different potentials
such systems and that further ionization (1 < k n, x ∗ k = n).
steps had be linked to structural changes
in the system [87]. Substitution effects, −xe
too, influence the position of the oxida- Mn −
−
−−−
1+
− (Mk )x , (10)
tion potentials of the polymers. Whereas E10
electron-donating substituents lower oxi- −xe
dation potentials just as they do in the −−
(Mk 1+ )x −−−
2+
− (Mk )x . (11)
E20
monomers, the electron-withdrawing sub-
stituents raise them. The fact that in the
majority of cases there is a linear rela- This concept implies negligible interaction
tion between the oxidation potentials for energies between the segments; conse-
the monomers and the polymers shows quently, the essential determinant of the
that the substituents’ effects are primarily position of the redox potentials must be
of an electronic nature [79, 90, 91]. Feld- the structure of the so-called effectively
berg and Rubinstein [92] offered another conjugated segments (ECS) [95].
explanation for the typical separation be- These ideas developed by chemists
tween anodic and cathodic peak potentials resemble the bipolaron model, which
of conducting polymers. In their opinion, presents the solid-state physicist’s view
the hysteresis is not due to a classic square of the electronic properties of doped
scheme involving a heterogeneous and ho- conducting polymers [96]. The model was
mogeneous kinetics but due to N-shaped originally constructed to characterize de-
free energy curves as a consequence of fects in inorganic solids. In chemical
phase transitions in the polymer. Later terminology, bipolarons are equivalent to
on, Gottesfeld et al. presented a model diionic states of a system (S = 0) after
in which they explained the hysteresis oxidation or reduction from the neutral
by consideration of resistive effects in the state. The transition from the neutral
polymer film. They suggested that the elec- state to the bipolaron takes place via
trochemistry is reversible and that the film the polaron state (= monoion, S = 1/2,
ESR signal) and, thus, corresponds se- Removing a second electron from the
quentially as well to redox transitions polymer segment results not in two po-
observed in two-step redox systems. In larons, but in the bipolaron, which is
contrast to normal redox processes, how- predicted to be energetically more favored
ever, additional local distortions occur in than the polaron. The reason for this lies in
the chain during the charging of the the respective structural relaxations: that
polymer. Already in the first step, the for the bipolaron is considerably greater
formation of polarons, there is a gain of than that for the polaron. The ionization
relaxation energy Erel. . This is released energy required to remove a second elec-
by structural relaxation after ionization, tron decreases, or the electron affinity for
for which a vertical Franck–Condon- taking up a second electron increases. In
like ionization energy EIP−v is neces- addition, it is assumed that the locally dis-
sary. Erel. corresponds to the bonding torted bipolaron state comprises only four
energy of the polaron [96]. The struc- or five units of a chain segment (Fig. 10).
tural relaxation causes a local distor- The energy gain of the bipolaron com-
tion of the chain in the vicinity of the pared with two polarons is said to be
charge, whereby the twisted benzoid- about 0.45 eV in the case of polypyrrole [97]
like structure of the affected segments and 0.35 eV in the case of polyparapheny-
transforms into a quinoid-like structure lene [96a]. In terms of redox energies,
in which the single bonds between the this means that the redox potentials E20
monomeric units shorten and assume for bipolaron formation should be much
double-bonding character. lower than the potential E10 for polaron
X X X X
X X X X
−e E 01
X X • X X
X X X X
Polaron
(monoion)
−e E 02
X X X X
X X X X
Bipolaron
(diion)
Fig. 10 Formation of the bipolaron (= diion) state in PPy or PTh
upon oxidation. In the model, it is assumed that the ionized states are
stabilized by a local geometrical distortion from a benzoid-like to a
quinoid-like structure. Hereby, one bipolaron should
thermodynamically become more stable than two polarons despite the
Coulombic repulsion between two similar charges.
formation. The model is based on the ideal oligomers and polymers. Thus, the spectra
assumption that the chain length of the of short oligomers of thiophenes are very
linear polymer is infinite, which results, as similar to those of polymers [104]. The
far as electronic properties are concerned, long-wavelength transitions of oligomers
in a band structure. During charging, po- are continuously shifted to lower energies
laron and bipolaron states develop in the as a function of chainlength. Only the in-
bandgap region, which leads to character- tensities of the band increases because
istic optical transitions. of the fact that the transition moment is
Whereas the intermediate existence of polarized parallel to the chain, the band
polarons (= radical ions) has been un- shapes do not change on going from
equivocally proved by ESR measurements oligomers to polymers. Consequently,
and optical absorption spectra, up to now there is no necessity to apply the band
the existence of bipolarons has been only model (bipolaron model) instead of well-
indirectly deduced from the absence of established ‘‘molecule’’ models. Finally,
the ESR signal and the disappearance of the fact that the chain lengths of con-
the visible polaron band from the optical ducting polymers do not exceed numbers
absorption spectra [98, 99]. On the other of 30 to 50 supports the view that these
hand, spinfree – diionic charge – states in materials should be handled as molecular
aromatics, whose optical properties bear systems [70, 71, 104d, 105].
a remarkably resemblance to the predic- A major barrier to a conclusive inter-
tions of the bipolaron model, have long pretation of voltammetric data on con-
been known [100]. Theoretical calculations jugated conducting polymers was the
of optical transitions in conjugated (chain- lack of measurements for well-defined
like) systems show that transitions of model systems. A very important step was
radical ions or diions are in principle sim- the measurement of charging/discharging
ilar to those predicted by the bipolaron behavior of oligomers of the phenylene-
model [101]. A strong argument against vinylene type [89a, 106] as well as of
the validity of the bipolaron model is the conjugated oligomers in different chain-
fact that conductivity in highly doped poly- like series [5, 24, 107]. All these data clearly
mers decreases drastically [102]. (Fig. 11) demonstrate that the redox behavior of
According to the predictions of the model, such oligomers and polymers depend on
the conductivity should increase at a the chain length of the systems (Fig. 10).
higher doping level, owing to better over- They complement theoretical and exper-
lap between the bipolaron and the valence imental results already presented in the
band [96c]. So far, electrochemical mea- older literature [87, 88, 108].
surements have not provided any direct The following trends have been estab-
proof for the formation of a bipolaron state lished as a function of increasing chain
in conjugated oligomers and polymers. length. Firstly, redox states of identical
Similarly, electrochemical and ESR spec- charge (e.g., mono- or diion) shift towards
troscopic studies by Nechtschein et al. in- lower energies. Obviously, the redox ener-
dicate that the bipolaron state is not much gies of different states gradually approach
more stable than the polaron state [103]. a common convergence limit with in-
Additional strong arguments against the creasing chain length. Secondly, adding
validity of the bipolaron model are re- successive monomeric subunits in the
sulting from optical UV–vis spectra of molecular chain enlarges the number of
H3CO
S
S
n
OCH3
1 µA
−1.0 −0.5 0.0 0.5 1.0 1.5 2.0 2.5

E (vs Ag/AgCl)
[V]
3.5 E-2
I
II
1/R [s]
I
II
0.0
−1.0 1.0 3.0
E
[V]
Fig. 11 Cyclic voltammetry and in situ conductivity measurements of
poly-(4,4 -dimethoxy-bithiophene) in CH2 Cl2 , 0.1 M TBAPF6 , v = 5 mV s−1 , T = 273 K:
(a) cyclic voltammogram containing a background curve without polymer;
(b) conductance as function of potential, measured during potentiodynamic cycling.
accessible redox states, and thirdly, the states. All experimental data reveal – in
energy gap widens considerably between excellent agreement with quantum me-
the lowest and the highest charged states. chanical calculations – that the generation
This is a consequence of the Coulom- of higher redox states essentially requires
bic repulsion created by every new excess more or at least the same energy (in the
charge introduced into the system and con- case of long conjugated chains with n ≥ 8)
tradicts the predictions of the bipolaron than the formation of the monoionic (po-
model. Moreover, in experiments in so- laron) state.
lution, the stabilization of diionic states For real polymer systems – characte-
does not increase relative to monoionic rized by a more or less broad distribution
of molecular weight and, depending on the species reversibly dimerize and form en-
conditions of formation, various structural ergetically stabilized σ -intermediates [42,
defects – this means that at the start of 43]. Depending on the structure of the
charging there is a high density of virtually at least doubly charged σ -‘‘dimers’’, their
degenerated redox states, which generates discharging occurs at considerably lower
the peak-shaped anodic wave. As potential potentials than oxidation (or reduction) of
increases, the density of the redox states the neutral starting compound, produc-
decreases but remains finite within the ing a strong hysteresis between charg-
experimentally accessible potential range. ing and discharging of the respective
This explains the broad plateaulike waves oligomers. During the discharging pro-
that are so often characteristic of the cess, the σ -bonds between the chains
potential range following the peaklike break, and the system relaxes into its
main wave in voltammetric experiments. aromatic ground state. Even for small
Unequivocal experimental evidence for equilibrium constants between dimer and
this interpretation has been obtained monomer (K < 100) under solid-state con-
from voltammetric measurements carried ditions, a predominant amount of the
out under solid-state conditions on a charged species is transformed into the
series of oligophenylenevinylenes [89b]. ‘‘dimeric’’ state, because of the high sur-
face concentrations of the oligomers or
The voltammograms clearly show that
polymers. Therefore, voltammetric solid-
with increasing chain length the waves of
state experiments very often show the
succeeding redox steps superimpose and
characteristic hysteresis between charging
finally yield peak-shaped voltammograms
and discharging. A critical evaluation of all
involving the broad current plateau at
relevant data gives evidence that σ -dimers
higher charging levels (Fig. 12).
are formed in the equilibrium state, not
It is interesting to note that all the solid-
π-dimers, as postulated in the literature
state voltammograms in this experiment,
some years ago [41, 110]. They are the
both of the monodisperse oligomers and key intermediates of the radical–radical
the polymer, again show the same hys- coupling mechanism (see Scheme 2). In
teresis as has been observed for many the past, it was assumed that the de-
polymers such as PPy or PTh (see Fig. 9). protonation of such intermediates is fast,
Originally, these phenomena were inter- leading to a rearomaticized coupling prod-
preted as redox-related structural changes uct. All recent measurements carried out
within the solid film. It was assumed that with linear thiophene oligomers reveal that
during charging the polymeric chains sta- the deprotonation rate constants become
bilized through transition from a benzoid considerably smaller than the coupling
into a quinoid-like structure and become rate constants as the chain length of
planar and that, therefore, the discharging the oligomer increases [111]. Thus, the
process occurs at a considerably lower po- hexathiophene, and even more so, the oc-
tential. Obviously, this seemed to be the tathiophene, coupling products are stable
missing link in the evidence of the bipo- as long as the oligomers are only weakly
laron model [68, 5, 107b,c, 109]. charged (y ∼ 0.1). Besides the hysteresis,
However, quite another picture results these new findings explain all important
from recent studies of soluble oligomers, electrochemical, electronic, and optical
which clearly show that their oxidized properties of conducting polymers. They
0.2 µA
n=3
0.1 µA
n=4
0.005 µA
n=5
−3.5 −3.0 −2.5 −2.0 −1.5

n=6
E (vs Ag/AgCl)
(a) [V]
0.01 µA
n = ? (∞)
−3.5 −3.0 −2.5 −2.0 −1.5 −1.0

E (vs Ag/AgCl)
(b) [V]
Fig. 12 Reduction of oligophenylenevinylenes (OPV) (a) in solution THF, 0.1 M
TBAPF6 and (b) in the solid-state DMA, 0.1 M TBABr T = 208 K, v = 0.1 V s−1 .
The vertical dashed line indicates the convergence limit of E01 for the OPVs in
solution. The number of redox states increases as a function of chain length. For
OPV with n = 6, a heptaanion formation is observed. [From Ref. [80b].]
overcome the massive, and frequently crit- models correlated with periodic lattice
icized, inconsistencies of the bipolaron properties as applied in the case of crys-
model [40, 5, 112–114]. A major advan- talline solids. It should be kept in mind
tage of this new view on the properties that conducting polymers are amorphous
of conducting polymers is its excellent materials.
agreement with findings in (physical) Closely connected with the problems
organic chemistry, without reference to of the charge storage mechanism is the
question to what extent one must and but is also influenced by environmental pa-
can distinguish between faradaic and ca- rameters such as the solvent or supporting
pacitive processes during charging and electrolyte [119–123].
discharging [7a, 33c, 115–117]. Feldberg, From the respective doping levels one
in particular, holds that it is hardly possi- can deduce that, on the oxidation of PPy,
ble to draw such a distinction, and that the and often on that of PTh as well, every third
capacitive charge portion is proportional to or fourth heterocycle is charged, whereas
the amount of the oxidized polymer [118]. in the case of PPP (poly-p-phenylene) pro-
He concludes from a comparison with vided that the experiments take place in
optical data that the faradaic oxidation common solvents such as propylene car-
processes in CV experiments are essen- bonate, only every sixth monomeric unit
tially limited to the range of the ‘‘peak- is charged [121]. In contrast, if one uses
shaped’’ anodic wave, whereas the adjoin- SO2 , a solvent with low nucleophilicity,
ing broad anodic tail represents the large PPP can be reversibly oxidized to a doping
double-layer capacity of the system. The level of 0.24, which corresponds formally
solid-state experiments just mentioned to a charge on every fourth monomer
provide strong evidence that the current unit [124]. The differences in chargeabil-
plateau is due to faradaic processes [89b]. ity of PPP and PPy are explained by the
high oxidation potential of PPP. This sig-
Similar conclusions must be drawn
nificantly increases the reactivity of this
from charging/discharging experiments
system towards the solution and other nu-
with poly(4,4 -dimethoxybithiophene), in
cleophilic impurities. One should note that
which, at the end of the anodic charging in
polymers such as PA and PPP can be more
the plateaulike region, the current drops
highly charged by reduction (n-doping)
to almost zero (Fig. 11) [33c].
than by oxidation.
A further characteristic for charge stor-
Moving to a higher doping level, for
age in conducting polymers is the amount
example, 0.5, forces a charge in every
of doping and insertion. This gives second monomeric subunit, which, of
the mole fraction of the corresponding course, induces a coulombic repulsion.
monomers, whose charge is compensated Therefore, to achieve this, a higher elec-
by incorporated counterions; in the case trode potential must be applied. And
of p-doping (oxidation), the counterions this, normally, results in overoxidation
are anions. The doping level is deter- effects [125]. Through the overoxidation
mined either by elementary analysis or process, a degradation of the polymer
by coulometric measurements. However, occurs, often induced by nucleophilic sol-
these measuring techniques may pro- vents such as water or nitriles. Therefore,
duce different results, as the elementary overoxidized materials can be discharged
analysis cannot distinguish an additional only to a limited extent, which is a serious
solvent portion or organic coions, such as drawback for applications. In principle, a
tetraalkylammonium ions, and coulome- doping level of 1 should be possible. That
try also includes the capacitive charging. means that every monomeric unit bears a
The optimum doping level for PPy or PTh positive charge after doping. Up to now,
is about 0.33, but can have very much lower only the very stable poly(4,4-dimethoxy-
values. This depends, inter alia, on struc- bithiophene) system has been charged up
ture and the applied charging potential, to this doping level [33c]. A characteristic
feature of such a perfectly charged system positive potentials than those observed in
is that the faradaic current drops to zero the steady state within a voltammetric mul-
after passing the highest available redox tisweep experiment. Memory effects have
state. (Fig. 11) been observed in different materials, for
A very important electrochemical phe- example, polypyrrole, polythiophene, and
nomenon, which is not well understood, PANI. It is a very general property of
is the so-called memory effect. This means conducting polymers. In the literature, dif-
that the charging/discharging response of ferent explanations have been presented.
a conducting polymer film depends on the Heinze et al. [107b] suggested a relaxation
history of previous electrochemical events. from a twisted to a planar form during
Thus, the first voltammetric cycle ob- charging and vice versa during discharg-
tained after the electroactive film has been ing. Zotti et al. discussed an expulsion of
held in its neutral state differs markedly solvent leading to a shrinkage of the poly-
in shape and peak position from subse- meric matrix [127] and Baudoin attributed
quent ones [126]. Obviously, the waiting the relaxation to the ion pair content
time in the neutral state of the system of the film [128]. In a subsequent study,
is the main factor determining the ex- Nechtschein and Odin showed that the
tent of a relaxation process. During this ion pair formation is inconsistent with data
waiting time, which extends over several obtained in different electrolytes [129]. In
decades of time (1–105 s), the polymer addition, they found that the relaxation
slowly relaxes into an equilibrium state. does not depend on whether the poten-
(Fig. 13) After relaxation, the first oxida- tial is imposed or left free during the
tion wave of the polymer appears at more relaxation. In a similar model, Otero and
coworkers modified these interpretations
and suggested that when a polymer film is
oxidized, electrons are extracted from the
STW
polymeric chain generating polarons and
t = 30 s bipolarons, reorganizing double bonds
t = 300 s and angles between monomeric units
t = 3000 s given rise to conformational movements.
t = 10000 s Free volume is generated and counterions
and solvent penetrate by diffusion con-
50 µA trol from the solution: the polymer swells.
If the oxidized polymer is reduced by a
potential sweep, opposite processes take
place and the polymer shrinks; meanwhile,
counterions move toward the solution by
Fig. 13 Memory effect in cyclic
voltammetry: poly(3-methylthiophene)
in CH3 CN/0.1 M TBAPF6 ,
v = 20 mV s−1 . The solid line
corresponds to the steady state. The
broken lines show the voltammetric
−0.2 0.9 response after different relaxation
E (waiting) times τ at a potential of
[V] −0.200 mV. [From Ref. [128].]
diffusion control [130]. In a very recent the immobile anions, (Eqs. 12 – 13).
paper, Heinze et al. [131] presented exper-
imental details, which support the view [(PPy)4 + A− ]n + (n − m)e− −−−→
that σ -intermediates formed during the − −
m[(PPy)m+
4n mA ] + (n − m)Asol (12)
charging process are the cause for the
− − +
slow relaxation processes during discharg- [(PPy)m+
4n mA ] + me + mM −−−→
ing. It is well known that σ -intermediates
(PPy)4n + m[M+ , A− ]film (13)
are formed during charging of conducting
polymers with high rates because of the
Using polymeric or large anions dur-
fact that the concentration of the charged
ing electropolymerization, a pure cation
species lies between 1 and 10 M−1 . On the transport generally results upon anodic
other hand, the stability of σ -dimers in- charging and discharging [136]. This has
creases as a function of chain length. Their been confirmed by in situ monitoring of
decay under solid-state conditions during the mass change during electrochemical
discharging may be a very slow process. switching using a quartz crystal microbal-
As already mentioned, the princi- ance [137].
ple of electroneutrality must be ful- Electrochemical measurements of PANI
filled in charged polymers. Consequently, produce a picture of the charge storage
in freshly prepared p-doped polymers, mechanism that differs fundamentally
anions must compensate the positive from that obtained using PPy or PTh.
charges within the polymeric chains. How- In the cyclic voltammetric experiment,
ever, spectroelectrochemical studies [132], one observes two reversible waves in the
electrochemical quartz crystal microbal- potential range between −0.2 and +1.2 V
ance (EQCM) measurements [133], and versus SCE. Above +1.0 V, the current
SIMS and XPS measurements [134] on decreases to zero. Capacitive currents and
the mechanism of ion transport during overoxidation effects, as in the case of PPy
charging and discharging of conducting or PTh, do not occur [138]. The striking
polymers prove that discharging involves changes in the charge, characteristic of
not only the expulsion of anions but PANI compared with PPy and PTh,
also the incorporation of cations. In the are largely explained by the nitrogen
case of small anions, this cation exchange atoms capturing a considerable part of
mechanism is surprising. Recent results the coulombic interaction between the
on structural peculiarities of PPy during charged centers.
charging [62, 72] indicate that PPy chains PANI is usually produced by the an-
‘‘dimerize’’ upon oxidation of the neu- odic oxidation of aniline in acidic aqueous
tral chains, forming σ -bonds between the solution [5, 139], but can also be pro-
chains, and that, therefore, immobile lo- duced by chemical oxidation [138b, 140].
calized charges are generated, which, in Hence, it is not surprising that the oxida-
turn, prevent any movement of the anionic tion of PANI is pH-dependent and that,
counterions [135]. In consequence, dur- therefore, in addition to electron-transfer
ing the first discharging process, mobile processes, proton-transfer reactions occur
anions slowly diffuse out of the film; in during charging. Although it is usually
the second step, cations are incorporated assumed that PANI has a chain structure
into the polymer, forming ion pairs with (emeraldine) with head–tail connections
between the aniline units [141], the exis- technical applications have grown consid-
tence of cyclic structures has also been erably. Apart from the battery electrode,
postulated in the literature [142]. However, conducting polymers are discussed as po-
the synthesis and the characterization of tential ECD, antistatic materials, anticorro-
monodisperse aniline oligomers support sives, electrocatalysts, and light-emitting
the view of a linear chain in the nonox- materials. The most advanced develop-
idized state [141]. It is generally accepted ments are the battery [82, 146], antistatic
that there are different, possibly coexist- materials [147, 20d], and light-emitting de-
ing forms of PANI, including benzoid and vices [148].
quinoid rings, free amines (NH), imines, The attraction in the development of
and protonated amines and imines [143]. a rechargeable polymer battery lies in
Depending on the pH-value of the solu- the specific weight of polymers, which
tion, different protonated structures are is considerably lower than that of ordi-
formed. In the simplest case, it is as- nary inorganic materials, as well as the
potential environmental benefit. At the be-
sumed that polycationic states are formed
ginning of the battery research, the PA cell
in the first step [144]. In the second step,
was most extensively studied [2, 10]. How-
which correlates with the second oxida-
ever, owing to its chemical instability, it
tion peak in the CV-diagram, protons
has virtually no commercial prospects. A
are eliminated and additional electrons
promising candidate for a polymer battery
are abstracted (Scheme 4). This corre-
that does not possess the typical disad-
sponds with MacDiarmid’s observations, vantages of PA is PPy [119b, 149]. Its
which show that the second redox step open circuit voltage lies near 3.5 V ver-
is strongly pH-dependent [138b]. Shack- sus Li+ /Li. Charge capacity is about 70 to
lette et al. [145] showed in a very thorough 85 A h kg−1 , and the effective energy den-
study of the phenyl-end-capped tetramer sity reaches values of 40 to 60 W h kg−1 . A
of oligoaniline that the first oxidation step crucial disadvantage of PPy is that during
involves a 2e-transfer step, leading to the discharging cations are incorporated into
emeraldine salt form in which 50% of the polymeric layer, which leads to con-
the nitrogens are oxidized. The second sumption of the electrolyte and stops the
oxidation wave also indicates a 2e-step charging /discharging process in thin layer
and varies with pH at a rate of approx- cells. The reason for this phenomenon lies
imately 120 mV/pH, which suggests a in structural peculiarities of PPy, which
deprotonation of four protons. In this case, forms σ -dimers during charging, produc-
the resulting species should be the pure ing immobile positive charges correlated
imine form. with immobile anions [133c, 150].
An important problem encountered with
polymer electrodes is that of overoxida-
16.4 tion. It occurs after reversible charging of
Applications an electrode with high oxidation potentials
and leads to the degradation of the poly-
The starting point for applications was mer. The results of thorough studies [125,
the discovery that PA can function as an 151] show that such degenerative mecha-
active electrode [2] in a rechargeable poly- nisms are promoted by the nucleophilicity
mer battery. Since then, the prospects of of the solvent.
H+
− − − − +n H+ − − −
N N N N N N N N
−n H+
H H H H n H H H H n
−2n e− +2n e−
+• − +• −
N N N N
H H H H n
−2n e−, −n H+
+
− − − − +H
N N N N
−H+
H H n
− + + −
N N N N
H H H H n
−2n e−, −4n H+ +2n e−, +4n H+
− − − −
N N N N
n
Scheme 4 Redox steps during charging/discharging of PANI.

16.4 Applications
637
Apart from polymer batteries, applied 4. G. Tourillon, F. Garnier, J. Electroanal.

research on conducting polymers has Chem. 1982, 135, 173.
5. A.F. Diaz, J.A. Logan, J. Electroanal. Chem.
reached an advanced stage in the fields
1980, 111, 111.
of ECD [11, 152], antistatic layers [147], 6. A.J. Downard, D. Pletcher, J. Electroanal.
and light-emitting devices [148]. Elec- Chem. 1986, 206, 139.
trochromic displays are based on an elec- 7. (a) A.F. Diaz, J.I. Castillo, J.A. Logan, W.-Y.
trochemical reaction of a material that Lee, J. Electroanal. Chem. 1981, 129, 115;
(b) E.M. Genies, G. Bidan, A.F. Diaz, J. Elec-
displays a visual charge upon changing its troanal. Chem. 1983, 27, 330; (c) A.F. Diaz,
redox state. The advantages of using ECD J. Bargon in Handbook of Conducting Poly-
are their ease of preparation and the unifor- mers (Ed.: T.A. Skotheim), Marcel Dekker,
mity of the prepared films. Furthermore, New York, 1986, Vol. I, pp. 81–115.
ECDs have no limited visual angle, but con- 8. E.M. Genies, G. Bidan, A.F. Diaz, J. Elec-
troanal. Chem. 1983, 149, 101.
tinue to exhibit a memory function even 9. (a) K. Doblhofer, K. Rajeshwar in Handbook
after the driving voltage has been removed. of Conducting Polymers, 2nd ed.
Erasing and rewriting can be performed al- (Eds.: T.A. Skotheim, R.L. Elsenbaumer,
most at will. The suitability of PPy, PTh, J.R. Reynolds), Marcel Dekker, New
and PANI as ECD has been intensively York, 1998, pp. 531–588; (b) G.P. Evans
in Advances in Electrochemical Sciences
studied. PANI appears to be particularly and Engineering (Eds.: H. Gerischer,
promising, as its color changes during ox- C.W. Tobias), VCH Publishers, Weinheim,
idation range from yellow through green, 1990, pp. 1–74; (c) M.E.G. Lyons in
blue, and violet to brown [139c, 153]. Electroactive Polymer Chemistry (Ed.:
B. Scrosati), Chapman & Hall, London,
Baytron , a conducting polymer [154]
1994.
derived from 3,4-ethylenedioxythiophene, 10. (a) M. Maxfield, S.L. Mu, A.G. MacDiarmid,
is a commercially available product that J. Electrochem. Soc. 1985, 132, 838;
can be used as an antistatic or electrostatic (b) F. Beck in Advances in Electrochemical
coating of plastics and glass. Moreover, Science and Engineering (Eds.: R.C. Alkire,
H. Gerischer, D.M. Kolb), Wiley-VCH Pub-
it has successfully been applied as coun-
lishers, Weinheim, 1997, Vol. 5, pp.
terelectrode in capacitors and as a hole- 303–411.
injection layer in organic light-emitting 11. (a) R.J. Mortimer, Electrochim. Acta 1999,
diodes [155]. 44, 2971; (b) M.A. DePaoli, G. Casalbore-
Miceli, E.M. Girotto, W.A. Gazotti, Elec-
trochim. Acta 1999, 44, 2983; (c) F. Garnier,
References G. Tourillon, M. Gazard, J.C. Dubois, J.
Electroanal. Chem. 1983, 148, 299.
1. (a) H. Shirakawa, E.J. Louis, A.G. MacDi- 12. B.B. Wessling, Synth. Met. 1998, 93, 143.
armid, C.K. Chiang, A.J. Heeger, J. Chem. 13. (a) P.N. Bartlett, S.K. Ling-Chung, Sens. Ac-
Soc., Chem. Commun. 1977, 578; (b) C.K. tuators 1989, 20, 287; (b) J.N. Barisci,
Chiang, Y.W. Park, A.J. Heeger, H. Shi- C. Conn, G.G. Wallace, TRIP 1996, 4, 307.
rakawa, E.J. Louis, A.G. MacDiarmid, J. 14. R. Noufi, J. Electrochem. Soc. 1983, 130,
Chem. Phys. 1978, 69, 5098. 2126.
2. (a) P.J. Nigrey, A.G. MacDiarmid, A.J. 15. V.G. Kulkarni, Handbook of Conducting
Heeger, J. Chem. Soc., Chem. Commun. Polymers, 2nd ed. (Eds.: T.A. Skotheim,
1979, 594; (b) D. MacInnes Jr., M.A. Druy, R.L. Elsenbaumer, J.R. Reynolds), Marcel
P.J. Nigrey, D.P. Nairns, A.G. MacDiarmid, Dekker, New York, 1998, pp. 1059–1073.
A.J. Heeger, J. Chem. Soc., Chem. Commun. 16. (a) D. Halliday, P. Burn, D. Bradley,
1981, 317. R. Friend, O. Gelson, A. Holmes, A. Kraft,
3. A.F. Diaz, K.K. Kanazawa, G.P. Gardini, J. J. Martens, K. Pichler, Adv. Mater. 1993,
Chem. Soc., Chem. Commun. 1979, 635. 5, 41; (b) F. Hide, M.A. Diaz-Garcia,
16.4 Applications 639
B.J. Schwartz, M.R. Anderson, Q. Pei, A.J. P. Hapiot, P. Neta, J. Phys. Chem. B 1997,
Heeger, Science 1996, 273, 1833; (c) M.T. 101, 5698.
Bornius, M. Inbusekaran, J. O’Brien, 29. J. Heinze, P. Tschuncky in The Oligomer
W. Wu, Adv. Mater. 2000, 12, 1737. Approach (Eds.: K. Müllen, G. Wegner),
17. (a) W.J. Albery, A.R. Hillman, Annu. Rep. Wiley-VCH Publishers, Weinheim, 1998,
Prog. Chem., Sect. C 1981, 78, 377; pp. 479–514.
(b) R.W. Murray in Electroanalytical Chem- 30. (a) Z. Xu, D. Fichou, G. Horowitz, F. Gar-
istry (Ed.: A.J. Bard), Marcel Dekker, nier, J. Electroanal. Chem. 1989, 267,
New York, 1984, Vol. 13, pp. 191–368; 339; (b) G. Zotti, G. Schiavon, A. Berlin,
(c) A. Merz, Top. Curr. Chem. 1990, 152, G. Pagani, Synth. Met. 1993, 61, 81;
49. (c) G. Zotti, G. Schiavon, A. Berlin, G. Pa-
18. S.N. Bhadani, G. Parravano in Organic Elec- gani, Chem. Mater. 1993, 5, 430; (d) P. Gar-
trochemistry (Eds.: M.M. Baizer, H. Lund), cia, J.-M. Pernaut, P. Hapiot, V. Wintgens,
Marcel Dekker, New York, 1983, p. 995. P. Valat, F. Garnier, D. Delabouglise, J.
19. R.J. Waltman, J. Bargon, A.F. Diaz, J. Phys. Phys. Chem. 1993, 97, 513; (e) P. Hapiot,
Chem. 1983, 87, 1459. L. Gaillon, P. Audebert, J.J.E. Moreau, J.-P.
20. (a) S. Holdcroft, B.L. Funt, J. Electroanal. Lère-Porte, M.W. Chi Man, Synth. Met.
Chem. 1988, 240, 89; (b) Q. Pei, R. Qu- 1995, 72, 129.
ian, J. Electrochem. Soc. 1992, 322, 153; 31. P. Audebert, P. Hapiot, J.-M. Pernaut,
(c) W. Wernet, G. Wegner, Makromol. P. Garcia, J. Electroanal. Chem. 1993, 361,
Chem. 1987, 188, 1465; (d) L.B. Groenen- 283.
daal, F. Jonas, D. Freitag, H. Pielartzik, J.R. 32. P. Audebert, J.-M. Catel, G. Le Coustumer,
Reynolds, Adv. Mater. 2000, 12, 481. V. Duchenet, P. Hapiot, J. Phys. Chem.
21. A.J. Downard, D. Pletcher, J. Electroanal. 1995, 99, 11 923.
Chem. 1986, 206, 147. 33. (a) A. Smie, A. Synowczyk, J. Heinze,
22. (a) T. Osa, A. Yildiz, T. Kuwana, J. Am. R. Alle, P. Tschuncky, G. Götz, P. Bäuerle,
Chem. Soc. 1969, 81, 3994; (b) M. Dietrich, J. Electroanal. Chem. 1998, 452, 87;
J. Mortensen, J. Heinze, J. Chem. Soc., (b) J. Heinze, M. Dietrich, DECHEMA
Chem. Commun. 1986, 1131. Monogr. 1990, 121, 125; (c) M. Dietrich,
23. (a) C.K. Baker, J.R. Reynolds, J. Electroanal. J. Heinze, Synth. Met. 1991, 41–43, 503; (d)
Chem. 1988, 251, 307; (b) R. John, G.G. P. Tschuncky, J. Heinze, Synth. Met. 1993,
Wallace, J. Electroanal. Chem. 1991, 306, 157; 55, 1603; (e) A. Merz, S. Anikin, B. Lieser,
(c) P.M. Narula, R.E. Noftle, J. Electroanal. J. Heinze, H. John, Chem. Eur. J. 2003, 9
Chem. 1999, 464, 123. 449.
24. K. Müllen, G. Wegner, (Eds.), Electronic 34. J. Heinze, K. Hinkelmann, M. Dietrich,
Materials: The Oligomer Approach, Wiley- J. Mortensen, Ber. Bunsen-Ges. Phys. Chem.
VCH, Weinheim, 1998. 1985, 89, 1225.
25. Z.-G. Xu, G. Horowitz, J. Electroanal. Chem. 35. R.E. Niziurski-Mann, C. Scordilis-Kelley,
1992, 335, 123. T.-E. Liu, M.P. Cava, R.T. Carlin, J. Am.
26. M. Zhou, M. Pagels, B. Geschke, J. Heinze, Chem. Soc. 1993, 115, 887.
J. Phys. Chem. B 2002, 106, 10 065. 36. K. Meerholz, J. Heinze, Electrochim. Acta
27. (a) J. Heinze, Angew. Chem. 1993, 105, 1996, 41, 1839.
1337; Angew. Chem., Int. Ed. Engl. 1993, 37. M. Zhou, J. Heinze, J. Phys. Chem. B 1999,
32, 1268; (b) C. Amatore, E. Maisonhaute, 103, 8451.
G. Simonneau, Electrochem. Commun. 2000, 38. J. Heinze, K. Hinkelmann, M. Land,
2, 81. DECHEMA Monogr. 1989, 112, 75.
28. (a) C.P. Andrieux, P. Audebert, P. Hapiot, 39. (a) K. Imanishi, M. Satoh, Y. Yasuda,
J.-M. Savéant, J. Am. Chem. Soc. 1990, R. Tsushina, S. Aoki, J. Electroanal. Chem.
112, 2439; (b) C.P. Andrieux, P. Audebert, 1988, 242, 203; (b) R. Quian, Q. Pei,
P. Hapiot, J.-M. Savéant, J. Phys. Chem. Z. Huang, Makromol. Chem. 1991, 192,
1991, 95, 10158; (c) C.P. Andrieux, P. Hap- 1263; (c) C. Visy, J. Lukkari, J. Kankare,
iot, P. Audebert, L. Guyard, M. Nguyen Synth. Met. 1994, 66, 61.
Dinh An, L. Groenendaal, E.W. Meijer, 40. (a) M.G. Hill, K.R. Mann, L.L. Miller, J.-F.
Chem. Mater. 1997, 9, 723; (d) L. Guyard, Penneau, J. Am. Chem. Soc. 1992, 114, 2728;
(b) M.G. Hill, J.-F. Penneau, B. Zinger, G.K. Chandler, G.A. Gunawardena, D. Plet-
K.R. Mann, L.L. Miller, Chem. Mater. 1992, cher, J. Electroanal. Chem. 1984, 177, 229;
4, 1106; (c) B. Zinger, K.R. Mann, M.G. Hill, (c) M. Satoh, K. Imanishi, K. Yoshino,
L.L. Miller Chem. Mater. 1992, 4, 1113; J. Electroanal. Chem. 1991, 317, 139;
(d) L.L. Miller, K.R. Mann, Acc. Chem. Res. (d) Y. Wei, C.-C. Chan, J. Tian, G.W.
1996, 29, 417; (e) Y. Yu, E. Gunic, B. Zinger, Jang, K.F. Hsueh, Chem. Mater. 1991, 3,
L.L. Miller, J. Am. Chem. Soc. 1996, 118, 888; (e) B.R. Scharifker, E. Garcia-Pastoriza,
1013. W. Marino, J. Electroanal. Chem. 1991, 300,
41. (a) P. Bäuerle, U. Segelbacher, A. Maier, 85; (f) J.Y. Qiu, J.R. Reynolds, J. Polym. Sci.,
M. Mehring, J. Am. Chem. Soc. 1993, Part A: Polym. Chem. 1992, 30, 1315; (g)
115, 10 217; (b) P. Bäuerle, U. Segelbacher, G. Casalbore-Miceli, N. Camaione, A. Geri,
K.U. Gaudl, D. Huttenlocher, M. Mehring, A. Berlin, R. Campesato, Electrochim. Acta
Angew. Chem. Int. Ed. Engl. 1993, 32, 1999, 44, 4781.
76; (c) U. Segelbacher, N.S. Sariciftci, 47. P. Debye, Trans. Electrochem. Soc. 1942, 82,
A. Grupp, P. Bäuerle, M. Mehring, Synth. 265.
Met. 1993, 55–57, 4728; (d) J.A.E.H. Haare, 48. (a) M. Eigen, W. Kruse, G. Maas,
L. Groenendaal, E.E. Havinga, R.A.J. Jan- L. DeMayer in Progress in Reaction Kinetics
ssen, E.E. Meijer, Angew. Chem., Int. Ed. (Ed.: C. Porter), Pergamon Press, Oxford,
Engl. 1996, 35, 7638; (e) P. Hapiot, P. Au- 1964, pp. 284–318, Vol. 2; (b) J. Heinze
debert, K. Monnier, J.-M. Pernaut, P. Gar- in Microelectrodes: Theory and Applications,
cia, Chem. Mater. 1994, 6, 1549; (f) J.J. NATO ASI Series (Eds.: I. Montenegro,
Aperloo, R.A.J. Janssen, P.R.L. Malenfant, M.A. Queiros, J.L. Daschbach), Kluwer
L. Groenendaal, J.N.J. Fedet, J. Am. Chem. Academic Publishers, Dordrecht, 1991,
Vol. 197, pp. 283–294.
Soc. 2000, 122, 7042.
49. (a) P. Audebert, P. Hapiot, Synth Met. 1995,
42. (a) A. Smie, J. Heinze, Angew. Chem., Int.
75, 95; (b) P. Audebert, J.-M. Catel, G. Le
Ed. Engl. 1997, 36, 363; (b) J. Heinze,
Coustumer, V. Duchenet, P. Hapiot, J.
P. Tschuncky, A. Smie, J. Solid State
Phys. Chem. B 1998, 102, 8661.
Electrochem. 1998, 2, 102; (c) P. Tschuncky,
50. J.-C. Lacroix, F. Maurel, P.-C. Lacaze, J. Am.
J. Heinze, A. Smie, G. Engelmann, G. Ko-
Chem. Soc. 2001, 123, 1989.
ßmehl, J. Electroanal. Chem. 1997, 433, 223.
51. (a) S. Asavapiriyanont, G.K. Chandler, G.A.
43. A. Merz, J. Kronberger, L. Dunsch, A. Neu- Gunawardena, D. Pletcher, J. Electroanal.
deck, A. Petr, L. Parkanyi, Angew. Chem. Chem. 1984, 177, 245; (b) P.G. Pickup, R.A.
1999, 111, 1533; Angew. Chem., Int. Ed. Engl. Osteryoung, J. Am. Chem. Soc. 1984, 106,
1999, 38, 1442. 2294.
44. (a) F. Effenberger, K.-E. Mack, R. Niess, 52. A.R. Hillman, E.F. Mallen, J. Electroanal.
F. Reisinger, A. Steinbach, W.-D. Stohrer, Chem. 1987, 220, 351.
J.J. Srezowski, I. Rommel, A. Maier, J. Org. 53. A. Thyssen, A. Borgarding, J.W. Schultze,
Chem. 1988, 53, 4379–4386; (b) F. Effen- Chem. Macromol. Symp. 1987, 8, 143.
berger, F. Reisinger, K.H. Schönwälder, 54. (a) M. Fleischmann, H.R. Thirsk in Ad-
P. Bäuerle, J.J. Stezowski, K.H. Jogun, vances in Electrochemistry and Electrochem-
K. Schöllkopf, W.-D. Stohrer, J. Am. Chem. ical Engineering (Ed.: P. Delahay), Wiley-
Soc. 1987, 109, 882–892; (c) F. Effenberger, Interscience, New York, 1963, Vol. 3, p. 123;
W.-D. Stohrer, K.-E. Mack, F. Reisinger, (b) J.W. Schultze, M.M. Lohrengel, D. Roß,
W. Seufert, H.E.A. Kramer, R. Föll, E. Vo- Electrochim. Acta 1978, 28, 973.
gelmann, J. Am. Chem. Soc. 1990, 112, 55. J. Lukkari, M. Alanko, V. Pitkänen, K. Klee-
4849–4857; (d) F. Effenberger, P. Bäuerle, mola, J. Kankare, J. Phys. Chem. 1994, 98,
W. Seufert, W.-D. Stohrer, Chem. Ber. 1990, 8525.
123, 193–200; (e) F. Effenberger, Acc. Chem. 56. P. Lang, F. Chao, M. Costa, F. Garnier,
Res. 1989, 22, 27–35. Polymer 1987, 18, 668.
45. J. Heinze, C. Willman, P. Bäuerle, Angew. 57. A.O. Patil, A.J. Heeger, F. Wudl, Chem. Rev.
Chem., Int. Ed. 2001, 40, 2861. 1988, 88, 183.
46. (a) T. Inoue, T. Yamase, Bull. Chem. Soc. 58. A. Hamnett, A.R. Hillman, J. Electrochem.
Jpn. 1983, 56, 985; (b) S. Asavapiriyanont, Soc. 1988, 135, 2517.
59. (a) A.R. Hillman, E.F. Mallen, H.A. Ham- J. Phys. Chem. 1983, 87, 2289; (c) H. Neuge-
nett, J. Electroanal. Chem. 1988, 244, 353; bauer, G. Nauer, A. Neckel, G. Tourillon, F.
(b) A.R. Hillman, E.F. Mallen, J. Electroanal. Garnier, P. Lang, J. Phys. Chem. 1984, 88,
Chem. 1988, 243, 403. 652.
60. D.D. Cunningham, A. Galal, C.V. Pham, 78. H. Hotta, T. Hosaka, W. Shimotsuma, J.
E.T. Lewis, A. Burkhardt, L. Laguren- Chem. Phys. 1984, 80, 954.
Davidson, A. Nkansah, O.J. Ataman, 79. T.A. Skotheim, R.L. Elsenbaumer, J.R.
H. Zimmer, H.B. Mark Jr., J. Electrochem. Reynolds, (Eds.), Handbook of Conducting
Soc. 1988, 135, 2750. Polymers, 2nd ed., Marcel Dekker, New
61. R.E. Noftle, D. Pletcher, J. Electroanal. York, 1998.
Chem. 1987, 227, 229. 80. (a) W.K. Ford, C.B. Duke, W.R. Salaneck, J.
62. M. Zhou, J. Heinze, Electrochim. Acta 1999, Chem. Phys. 1982, 77, 5030; (b) J.J. Ritsko,
44, 1733. J. Fink, G. Crecelius, Solid State Commun.
63. S.W. Feldberg, J. Phys. Chem. 1971, 75, 1983, 46, 477.
2377. 81. A. Nazzal, G.B. Street, J. Chem. Soc., Chem.
64. J. Heinze, A. Rasche, H. John, M. Pagels, Commun. 1984, 83.
publication in preparation. 82. F. Beck in Advances in Electrochemical
65. O. Hammerich, R.M. Henriksen, F.S. Science and Engineering (Eds.: C. Alkire,
Kumounah, G.H. Hansen, T. Lund, 200 H. Gerischer, D.M. Kolb, C.W. Tobias),
ECS Meeting, San Francisco, September Wiley-VCH, Weinheim, 1997, Vol. 5, pp.
2–7 2001, Abstract 1169. 303–411.
66. C. Kvarnström, R. Bilger, A. Ivaska, J. 83. (a) A.T. Hubbard, F.C. Anson in Electroan-
alytical Chemistry (Ed.: A.J. Bard), Marcel
Heinze, Electrochim. Acta 1998, 43, 355.
Dekker, New York, 1970, p. 129, Vol. 4;
67. (a) C. Visy, J. Lukkari, J. Kankare, Synth.
(b) R.F. Lane, A.T. Hubbard, J. Phys. Chem.
Met. 1997, 87, 81; (b) B.R. Scharifker,
1973, 77, 1401; (c) E. Laviron, J. Electroanal.
D.J. Fermı́n, J. Electroanal. Chem. 1994, 365,
Chem. 1979, 100, 263; (d) H. Angerstein-
35.
Kozlowska, J. Klinger, B.E. Conway, J. Elec-
68. K. Meerholz, J. Heinze, Angew. Chem., Int.
troanal. Chem. 1977, 75, 45, 61.
Ed. Engl. 1990, 29, 692; Angew. Chem. 1990,
84. (a) F.B. Kaufman, A.H. Schroeder, E.M.
102, 655.
Engler, S.R. Kramer, J.Q. Chambers, J. Am.
69. K. Meerholz, J. Heinze, Synth. Met. 1993, Chem. Soc. 1980, 102, 483; (b) P. Daum, J.R.
55–57, 5040. Lenhard, D.R. Rolison, R.W. Murray, J. Am.
70. M. Akimoto, Y. Furukawa, H. Takeuchi, Chem. Soc. 1980, 102, 4649; (c) P. Daum,
I. Harada, Y. Soma, M. Soma, Synth. Met. R.W. Murray, J. Phys. Chem. 1981, 85, 389.
1986, 15, 353. 85. K. Doblhofer, K. Braun, R. Lange, J. Elec-
71. G. Zotti, G. Schiavon, A. Berlin, G. Pagani, troanal. Chem. 1986, 206, 93.
Chem. Mater. 1993, 5, 620. 86. E.M. Genies, A.A. Syed, Synth. Met. 1984,
72. M. Zhou, J. Heinze, J. Phys. Chem. B 1999, 10, 21.
103, 8443. 87. J.L. Brédas, R. Silbey, D.S. Boudreaux, R.R.
73. M. Zhou, V. Rang, J. Heinze, Acta Chem. Chance, J. Am. Chem. Soc. 1983, 105, 6555.
Scand. 1999, 53, 1059. 88. A.F. Diaz, J. Crowley, J. Bargon, G.P.
74. (a) A.F. Diaz, A. Martinez, K.K. Kanazawa, Gardini, J.B. Torrance, J. Electroanal. Chem.
M. Salmon, J. Electroanal. Chem. 1981, 130, 1981, 121, 355.
181; (b) T.C. Clarke, J.F. Scott, G.B. Street, 89. (a) J. Heinze, J. Mortensen, K. Müllen,
IBM J. Res. Dev. 1983, 27, 313. R. Schenk, J. Chem. Soc., Chem. Commun.
75. G.B. Street in Handbook of Conducting Poly- 1987, 701; (b) K. Meerholz, H. Gregorius,
mers (Ed.: T.A. Skotheim), Marcel Dekker, K. Müllen, J. Heinze, Adv. Mater. 1994, 6,
New York, 1986, pp. 265–291. 671.
76. P. Pfluger, G.B. Street, J. Chem. Phys. 1984, 90. M. Salmon, M.E. Carbajal, J.C. Juarez, A.F.
80, 544. Diaz, M.C. Rock, J. Electrochem. Soc. 1984,
77. (a) T. Yamamoto, K. Sanechika, A. Ya- 131, 1802.
mamoto, J. Polym. Sci., Polym. Lett. Ed. 91. G. Tourillon, F. Garnier, J. Electroanal.
1980, 18, 9; (b) G. Tourillon, F. Garnier, Chem. 1984, 161, 51.
92. S.W. Feldberg, I. Rubinstein, J. Electroanal. M. Hmyene, F. Deloffre, G. Horowitz,

Chem. 1988, 240, 1. P. Srivastava, F. Garnier, Adv. Mater. 1994,
93. S. Gottesfeld, A. Redondo, I. Rubinstein, 6, 277; (c) A. Sassella, R. Tubino, A. Bor-
S.W. Feldberg, J. Electroanal. Chem. 1989, ghesi, C. Botta, S. Destri, W. Porzio, G. Bar-
265, 15. barella, Synth. Met. 1999, 101, 538; (d) E.E
94. K. Deuchert, G. Hünig, Angew. Chem., Int. Havinga, I. Rotte, E.W. Meijer, W. ten
Ed. Engl. 1978, 17, 875. Hoewe, H. Wynberg, Synth. Met. 1991, 41,
95. (a) H.-H. Hörhold, V. Scherf, R. Stockmann, 473; (e) J. Roncali, Chem. Rev. 1992, 92,
D. Weiß, Z. Chem. 1987, 26, 126; (b) E.M. 711; (f) N. Hosaka, H. Tachibana, N. Shiga,
Genies, J.-M. Pernaut, J. Electroanal. Chem. M. Matsumoto, Y. Tokura, Synth. Met.
1985, 191, 111. 1999, 101, 212; (g) M. Trznadel, A. Prón,
96. (a) J.L. Brédas, R.R. Chance, R. Silbey, Phys. M. Zagorska, Synth. Met. 1999, 101, 118;
Rev. 1982, B26, 5843; (b) J.L. Brédas, (h) E.E. Havinga, C.M.J. Mutsaers, L.W.
B. Thémans, J.M. André, Phys. Rev. 1983, Jenneskens, Chem. Mater. 1996, 8 769.
B27, 7827; (c) J.L. Brédas, G.B. Street, Acc. 105. (a) D. Iarossi, A. Mucci, L. Schenetti,
Chem. Res. 1985, 18, 308; (d) J.L. Brédas R. Seeber, F. Goldoni, M. Affronte, F. Na-
in Handbook of Conducting Polymers (Ed.: va, Macromolecules 1999, 32, 1390; (b)
T.A. Skotheim), Marcel Dekker, New York, D. Delabouglise, R. Garreau, M. Lemaire,
1986, pp. 859–913. New J. Chem. 1988, 12, 155.
97. J.L. Brédas, J.C. Scott, K. Yakushi, G.B. 106. (a) A. Bohnen, H.J. Räder, K. Müllen,
Street, Phys. Rev. 1984, B30, 1023. Synth. Met. 1992, 47, 37; (b) R. Schenk,
98. (a) J.C. Scott, P. Pfluger, M.T. Krounbi, G.B. H. Gregorius, K. Meerholz, J. Heinze,
Street, Phys. Rev. 1983, B28, 2140; (b) J.C. K. Müllen, J. Am. Chem. Soc. 1991, 113,
Scott, J.L. Brédas, K. Yakushi, P. Pfluger, 2634.
G.B. Street, Synth. Met. 1984, 9, 165. 107. (a) M. Baumgarten, K. Müllen, Top. Curr.
99. (a) J.H. Kaufman, N. Colaneri, J.C. Scott, Chem. 1992, 169, 1; (b) J. Heinze, M. Stö-
K.K. Kanazawa, G.B. Street, Mol. Cryst. Liq. rzbach, J. Mortensen, Ber. Bunsen-Ges.
Cryst. 1985, 118, 171; (b) I. Kulszewicz- Phys. Chem. 1987, 91, 960; (c) J. Heinze,
Bajer, M. Zagorska, F. Genoud, J. Kruszka, J. Mortensen, M. Störzbach in Electrochem-
K. Stocka, A. Pron, M. Nechtschein, Synth. ical Properties of Conducting Polymers
Met. 1990, 35, 129; (c) G. Zotti, G. Schiavon, (Eds.: H. Kuzmany, M. Mehring, S. Roth),
Synth. Met. 1989, 31, 347. Springer, Berlin, 1987, pp. 385–390.
100. (a) J. Heinze, H.W. Zimmermann, Ber. 108. G.J. Hoijtink in Advances in Electrochem-
Bunsen-Ges. Phys. Chem. 1977, 78, 321; istry and Electrochemical Engineering (Ed.:
(b) D. Distler, G. Hohlneicher, Ber. Bunsen- P. Delahay), Wiley-Interscience, New York,
Ges. Phys. Chem. 1970, 74, 960; (c) G.J. 1970, Vol. 7.
Hoijtink, P.J. Zandstra, Mol. Phys. 1960, 109. J. Heinze, Synth. Met. 1991, 41–43, 2805.
3, 371. 110. (a) G. Zotti, G. Schiavon, A. Berlin, G. Pa-
101 P. Cársky, R. Zahradnik, Top. Curr. Chem. gani, Chem. Mater. 1993, 5, 620; (b) G. Zotti,
1973, 43, 1. A. Berlin, G. Pagani, G. Schiavon, S. Zec-
102. (a) J. Heinze, K. Meerholz, A. Smie, to chin, Adv. Mater. 1993, 6, 231.
be published; (b) D. Ofer, T.M. Swager, 111. J. Heinze, H. John, D. Weiß, to be pub-
M.S. Wrighton, Chem. Mater. 1995, 7, 418; lished.
(c) D. Ofer, R.M. Crooks, M.S. Wrighton, J. 112. Y. Furukawa, J. Phys. Chem. 1996, 100,
Am. Chem. Soc. 1990, 112, 7869. 15644.
103. (a) M. Nechtschein, F. Devreux, F. Genoud, 113. A.J.W. Tol, Synth. Met. 1995, 74, 95.
E. Vieil, J.-M. Pernaut, E. Genies, Synth. 114. A.J.W. Tol, Chem. Phys. 1996, 208, 73.
Met. 1986, 15, 59; (b) F. Genoud, M. 115. J. Heinze, M. Dietrich, J. Mortensen,
Guglielmi, M. Nechtschein, E. Genies, Makromol. Chem., Macromol. Symp. 1987,
M. Salmon, Phys. Rev. Lett. 1985, 55, 118. 8, 73.
104. (a) H. Nakanishi, S. Sumi, S. Ueno, K. Ta- 116. (a) J. Tanguy, N. Mermilliod, M. Hoclet,
kimiya Y. Aso, T. Otsuboo, K Komaguchi, J. Electrochem. Soc. 1987, 134, 795;
M. Shiotani, N. Ohta, Synth. Met. 2001, 119, (b) J. Tanguy, N. Mermilliod, M. Hoclet,
413; (b) A. Yassar, P. Valat, V. Wintgens, Synth. Met. 1987, 18, 7; (c) J. Tanguy,
M. Slama, M. Hoclet, J.L. Baudouin, Synth. 134. (a) F. Chao, J.L. Baudoin, M. Costa, P. Lang,
Met. 1989, 28C, 145. Makromol. Chem. Macromol. Symp. 1987,
117. R.C.M. Jakobs, L.J.J. Janssen, E. Baren- 8, 173; (b) Q.-X. Zhou, C.J. Kolaskie, L.L.
drecht, Recl. Trav. Chim. Pays-Bas 1984, 103, Miller, J. Electroanal. Chem. 1987, 223, 283.
275. 135. J. Heinze, M. Zhou, B. Geschke, M. Pagels,
118. S.W. Feldberg, J. Am. Chem. Soc. 1984, 106, J. Phys. Chem. B 2002, 106, 10065.
4671. 136. (a) T. Shimidzu, A. Ohtani, T. Iyoda,
119. (a) G. Tourillon, F. Garnier, J. Phys. Chem. K. Honda, J. Electroanal. Chem. 1987, 224,
1983, 87, 2289; (b) R. Bittihn, G. Ely, 123; (b) F.F. Fan, A.J. Bard, J. Electrochem.
F. Woeffler, H. Münstedt, H. Naarmann, Soc. 1987, 133, 301.
D. Nägele, Makromol. Chem., Macromol. 137. (a) M. Lien, W.H. Smyrl, M. Morita, J. Elec-
Symp. 1987, 8, 51; (c) M. Salmon, A.F. Diaz, troanal. Chem. 1991, 309, 333; (b) C. Zhong,
A.J. Logan, M. Krounbi, J. Bargon, Mol. K. Doblhofer, Electrochim. Acta 1990 35,
Cryst. Liq. Cryst. 1982, 83, 1297. 1971.
120. T.C. Chung, J.H. Kaufman, A.J. Heeger, 138. (a) A. Kitani, J. Izumi, J. Yano, Y. Hiromoto,
F. Wudl, Phys. Rev. 1984, 30B, 702. K. Sasaki, Bull. Soc. Chem. Jpn. 1984,
121. R.L. Elsenbaumer, L.W. Shacklette in 57, 2254; (b) W.-S. Huang, B.D. Humphrey,
Handbook of Conducting Polymers (Ed.: T.A. A.G. MacDiarmid, J. Chem. Soc., Faraday
Skotheim), Marcel Dekker, New York, 1986, Trans. 1 1981, 82, 2385; (c) J. Heinze,
p. 213. J. Mortensen, K. Hinkelmann, Synth. Met.
122. F. Beck, M. Oberst, B. Braun, DECHEMA 1981, 21, 209.
Monogr. 1987, 109, 457. 139. (a) R. Noufi, A.J. Nozik, J. White, L.F.
123. A.G. MacDiarmid, M.R. Maxfield in Electro- Warren, J. Electrochem. Soc. 1981, 129, 2261;
chemical Science and Technology of Polymers (b) E.M. Genies, C. Tsintavis, J. Electroanal.
(Ed.: R.G. Linford.), Elsevier Applied Sci- Chem. 1986, 200, 127; (c) T. Kobayashi,
ence, London, 1987, pp. 67–101. H. Yoneyama, H. Tamura, J. Electroanal.
124. M. Dietrich, J. Mortensen, J. Heinze, J. Chem. 1984, 161, 419.
Chem. Soc., Chem. Commun. 1986, 1131. 140. R. DeSurville, M. Jozefowicz, L.T. Yu,
125. (a) F. Beck, P. Braun, M. Oberst, Ber. J. Perichon, R. Buvet, Electrochim. Acta
Bunsen-Ges. Phys. Chem. 1987, 91, 967; (b) 1968, 13, 1451.
B. Krische, M. Zagorska, Synth. Met. 1989, 141. F. Wudl, R.O. Angus Jr., F.L. Lu, P.M.
28C, 257. Allemand, D.J. Vachon, M. Nowak, Z.X.
126. (a) B. Villeret, M. Nechtschein, Phys. Rev. Liu, A.J. Heeger, J. Am. Chem. Soc. 1987,
Lett. 1989, 63, 1285; (b) M. Nechtschein, 109, 3677.
Synth. Met. 1990, 35, 129. 142. L. Dunsch, J. Electroanal. Chem. 1975, 61,
127. G. Zotti, G. Schiavon, Synth. Met. 1989, 31, 61.
347. 143. J.C. Chiang, A.G. MacDiarmid, Synth. Met.
128. J.L. Baudoin, F. Chao, M. Costa, J. Chim. 1986, 13, 193.
Phys. 1989, 86, 181. 144. D.S Boudreaux, R.R. Chance, J.F. Wolf,
129. C. Odin, M. Nechtschein, Synth. Met. 1991, L.W. Shacklette, J.L. Brédas, B. Thémans,
44, 177. J.M. André, R. Silbey, J. Chem. Phys. 1988,
130. (a) H. Grande, T.F. Otero, Electrochim. Acta 85, 4584.
1999, 44, 1893; (b) T.F. Otero, H. Grande, 145. L. W. Shacklette, F. F. Wolf, S. Gould, R. H.
J. Rodrigez, J. Phys. Chem. B 1997, 101, Baughman, J. Chem. Phys. 1988, 88, 3955.
8525. 146. P. Novak, K. Müller, K.S.V. Santhanam,
131. M. Pagels, J. Heinze, B. Geschke, V. Rang, O. Haas, Chem. Rev. 1997, 97, 207.
Electrochim. Acta 2001, 46, 3943. 147. H.H. Kuhn, A.D. Child in Handbook of
132. E.M. Genies, J.-M. Pernaut, Synth. Met. Conducting Polymers (Eds.: T.A. Skotheim,
1984, 10, 117. R.L. Elsenbaumer, J.R. Reynolds), Marcel
133. (a) J.H. Kaufman, K.K. Kanazawa, G.B. Dekker, New York, 1998, pp. 993–1013.
Street, Phys. Rev. Lett. 1984, 53, 2461; (b) 148. (a) R.H. Friend, N.C. Greenham in Hand-
S. Servagent, E. Vieil, J. Electroanal. Chem. book of Conducting Polymers (Eds.: T.A.
1990, 280, 227; (c) J. Heinze, R. Bilger, Ber. Skotheim, R.L. Elsenbaumer, J.R. Rey-
Bunsen-Ges. Phys. Chem. 1993, 97, 502. nolds), Marcel Dekker, New York, 1998,
pp. 823–845; (b) G. Leising, S. Tasch, Dekker, New York, 1986, pp. 673–687;
W. Graupner in Handbook of Conduct- (b) H. Yoneyama, K. Wakomoto,
ing Polymers (Eds.: T. A. Skotheim, H. Tamura, J. Electrochem. Soc. 1985, 132,
R.L. Elsenbaumer, J.R. Reynolds), Marcel 2414.
Dekker, New York, 1998, pp. 847–880. 153. (a) A. Kitani, J. Yano, K. Sasaki, J. Electro-
149. (a) S. Panero, P. Prosperi, F. Bonino, anal. Chem. 1986, 209, 227; (b) M. Kaneko,
B. Scrosati, Electrochim. Acta 1993, 32, H. Nakamura, Makromol. Chem., Rapid
1007; (b) T. Osaka, K. Naoi, S. Ogano, Commun. 1987, 8, 179.
S. Nakamara, J. Electrochem. Soc. 1993, 134, 154. M. Dietrich, J. Heinze, G. Heywang,
2096. F. Jonas, J. Electroanal. Chem. 1994, 369,
150. (a) F. Beck, M. Dahlhaus, J. Electroanal. 87.
Chem. 1993, 357, 289; (b) M. Hepel, Elec- 155. (a) Baytronics, Ed. 08/99, Order No.
trochim. Acta 1996, 41, 63. CH201303; (b) D. Quitens (Agfa-Gevaert),
151. K.H. Dietz, F. Beck, J. Appl. Electrochem. European Patent EP 0593111, 1994;
1987, 15, 159. (c) J. Friedrich, R. Dhein (Bayer) German
152. (a) M. Gazard in Handbook of Conduct- Patent DE 4229192, 1994.
ing Polymers (Ed.: T. Skotheim), Marcel

Organic Electrochemistry

Diunggah oleh

Informasi Dokumen

Hak Cipta

Format Tersedia

Bagikan dokumen Ini

Bagikan atau Tanam Dokumen

Opsi Berbagi

Apakah menurut Anda dokumen ini bermanfaat?

Apakah konten ini tidak pantas?

Hak Cipta:

Format Tersedia

Organic Electrochemistry

Diunggah oleh

Hak Cipta:

Format Tersedia

1

1.2 Why and How to Investigate Mechanisms of Electroorganic Reactions 4

1.3 How to Gain Access to Kinetics, Thermodynamics, and Mechanisms

1.3.3 Some Mechanistic Examples . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

1.4 How to Gain Additional Information about Electroorganic Reaction

1.1 molecular electrochemistry [1] or dynamic

Adsorption Diffusion layer Bulk

1.2.3 proﬁle. In general, the electrode is located

Fig. 2 Schematic representation of experimental set-up for

potentiostat in a three-electrode arrange- transport (diffusion) limited region. After

if the extrapolated Anson plot lines do not than chronoamperometry. Again, n, A, or

commercial instruments, and provide a Besides determination of n, A, or D,

current The fact that transport limits the rate

with tend denoting the time when the 1.3

• Concentration: The dependence of re- or are caused by non-Faradaic pro-

equation (7). Alternatively, a combination is assumed to be 0.5 in organic electrode

0 Fig. 9 Typical cyclic

redox-active units, which undergo ET at (for an oxidation; extension to reduction is

Fig. 11 The square scheme

1.3.3.3 Preequilibria to ETs Kinetics and thermodynamics will inﬂu-

the electroactive A leads to an increase mechanisms, simulation is an indispens-

R Quartz crystal with

Fig. 14 Set-up of an electrogravimetric experiment with an

diffusion components parallel to the sur- 1.4.3

ﬁlm formation on electrodes, support use in electroorganic chemistry. These

2.2 Target and Scale of the Investigations . . . . . . . . . . . . . . . . . . . . . 30

2.3 Principles of Electrochemical Cell Operation . . . . . . . . . . . . . . . . 31

2.4 Components of Electroorganic Reaction Systems . . . . . . . . . . . . . 38

2.5 Electrochemical Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

2.1 the beginning, literature data about com-

the oxidation at the anode and the re- 2.2

2 can be oxidized, increasing the current F = Faraday constant). The equilibrium

2.3.2.1.2 Overvoltage To obtain a cell only by diffusion and not by convection

oxidation of reactant 2, thick dotted lines, 2.3.2.1.5 Possible Problems in Electroor-

Anodic equilibrium potential

(possibly increased by gas bubbles)

Fig. 2 Composition of the cell voltage (not in real scale).

especially at constant concentrations ow- such as concentrations of reactants and

Fig. 3 Scheme of potentiostatic

with a reference electrode (RE, see

2.4.1 subsequent chemical reactions. All these

• Anodic oxidation of carboxylates in aqueous solution via decarboxylation

• Cathodic reduction of acrylonitrile in aqueous solution

Hg, Pb, C, Cd NC−(CH2)4−CN

2.4.1.1.3 Platinum, Platinum Metals or Anode A nickel anode forms in aqueous

Anode (lead dioxide) On lead as anode 2.4.1.1.7 Mercury

suitable electrode constructions. Its tech- machining (diamond tools necessary). It is

and therefore carbon can be a useful applications especially metals such as

Diamond coating (boron doped) A new

Solvent Abbreviation ε Potential limit [V]

1,2-Dimethoxyethane – 3.5 −3.0a +0.7a

2.4.2.2 Supporting Electrolytes But usually an inert supporting elec-

Tab. 2 Potential limits of some anions and cations of supporting

Ion Electrode Potential limit [V]

J− Pt anode 0.30a 0.20

a Resulting from standard potentials.

• low toxicity, and operation conditions, it may be

of polyethylene or polypropylene are cheap membrane (anion-exchange membrane),

With a small pressing force, a leakproof Various ﬂuoropolymer equipment, for

6 Fig. 4 Leakproof ﬁxing of PTFE tube in

Fig. 6 (From Ref. [4]) Positioning of the W

Fig. 12 Capillary gap cell (From

cathodes. The small electrode distance en-

2.5.2.4.3 Swiss Roll Cell This cell has