+

Carbon-Carbon Bond
Formation
+
C-C Bond formation
Hydrogen on a carbons to a carbonyl is
sufficiently acidic to be removed by a
strong base
O
C R'
R
H
+ Common bases: NaH, EtONa, NaNH2
Thestrong base LDA (lithium diisopropylamide)
able to form an enolates ion.
H
Li + N

Buyllithium Diisopropylamine
(BuLi) THF (pKa = 38)

Li
+ N

Butane Lithium diisopropylamine

(pKa = 50) [LDA or LiN(iPr)2]
+ -Hydrogen was removed by a strong base such as
LDA to form enolates ion.

The resulting anion is stabilized by resonance to

the carbonyl

O H O O
C C C C C C
R R R

B: Resonance structures for the delocalized enolates

Example:
 when ketone is not symmetrical, either -carbon
can be removed using base. This enolate is more stable
because the double bond is
more highly substituted. It is the
predominant enolate at
equilibrium.
Thermodynamic
enolate

kinetic
enolate
This enolate is formed faster
because the hindered strong
base removes the less
hindered proton faster.
+
Regioselectivity of enolate
formation
With the use of a bulky base, the less hindered hydrogen is
removed more rapidly, and the major product is the less
substituted enolate anion
+ Alkylation of enolates
Important in forming a carbon-carbon bond

Work well for primary alkyl halide, allylic and benzylic

halide (not work for tertiary halides)

O O O
LDA, THF R'' X
R o R R
H(R') -78 C H(R') H(R')
(formation of the R''
kinetic enolate)
Example;
 Two different products can be formed if the ketone is not
symmetrical
Enolate vs enamine
 Aldehydes & ketones react with
1o amines (and ammonia) to form imines
o
2 amines to form enamines
Alkylation of enamines

H+, H2O
+ Alkylation of hydrazones
Hydrazone anions are more reactive than corresponding
ketone or aldehyde enolate

Drawback:can be difficult to hydrolyze

+ Alkylation of heteroatom
stabilized anion
sulfones
+ Alkylation of heteroatom
stabilized anion
sulfoxides
+
C=C bond formation
1. Aldol condensation

2. Claisen condensation

3. Claisen rearrangement

4. Wittiq reaction

5. Peterson Olefination

6. Julia-Lythgoe Olefination

7. Mannich reaction
+
C=C bond formation
Aldol condensation

Addition between
2 aldehyde/ketone
+
claisen condensation

Addition-elimination
between 2 ester
+
claisen rearrangement
Allyl aryl ethers undergo a thermal rearrangement (200 -250
C ) to give ortho-allylphenols.

This reaction is an intramolecular process, result in alkylation

of the phenol in an ortho position

A sigmatropic rearangement is a reaction is which a bond

break (bond to allylic carbon) migrates from one end of a
system to the other.

Allyl aryl ethers ortho-allylphenols

+

A similar rearrangement takes place with allyl vinyl ether

a ,-unsaturated ketone or aldehyde results
+ Problems:
What products are expected from claisen
rearrangement of the following compound?
+
Wittig reaction
An aldehyde and ketone react with phosphorus ylides to
produced alkenes
Ylides is a neutral molecules with adjacent positive and
negative charges
R R" R R"
O + (C6H5)3P C C C
R' R" R' R"
aldehyde phosphorus ylide alkene
or ketone (or phosphorane) [(E) & (Z) isomers]
+
O P(C6H5)3

triphenyl-
phosphine
oxide
 Synthesis of Phosphorus ylides

R" R"
(C6H5)3P: + CH X (C6H5)3P CH X
R"' R"'
triphenyl- an alkyltriphenylphos-
phosphine phonium halide
 Mechanism of the Wittig reaction
R" R' R"
R R'
C + :C R"' R C C R"'
:O: P(C6H5)3 :O P(C6H5)3

:
aldehyde ylide oxaphosphetane
or ketone
R' R"
:

O P(C6H5)3 + C C
:

R R"
triphenylphosphine alkene
oxide (+ diastereomer)
Problems:
What products are expected from wittig reaction of
the following compound?
+
Peterson olefination
the preparation of alkenes from -silylcarbanions and
carbonyl compound.

Peterson olefination offers the possibility of improving the

yield of the desired alkene stereoisomer by careful
separation of the two diastereomeric -hydroxy silanes and
subsequently performing two different eliminations.

Remove Me3SiO
+
+
Julia-Lythgoe Olefination
The Julia-Lythgoe olefination involves the nucleophilic
addition of lithiosulfones to carbonyl compounds, acylation,
and reductive treatment of the resulting -acyloxysulfones

Sodium amalgam or samarium diiodide is generally used for

the reduction.
+
Carbonyl Coupling Reactions
(McMurry Reaction)
the reaction of two carbonyl groups to establish a new
double bond.

reductive coupling of carbonyls with low valent transition

metals, Ti(0) or Ti(II), to give olefins

excellent method for the preparation of strained (highly

substituted) olefins - Intramolecular coupling gives cyclic
olefins

the (E)-isomer of product is favored over the (Z)-isomer

TiCl3 and LiAlH4

(Z)-isomer (E)-isomer
+ Mechanism:

Examples:
+
Mannich reaction

Mannich reaction is a condensation reaction in which a non-

enolizable aldehyde,1o or 2o amine and a enolizable carbonyl
compounds reacts to yield a amino methylated products.

This reaction is also called amino alkylation.

The product obtained in this reaction is -amino carbonyl

compound which is also called Mannich base.
+
+ Examples:

Problems:

?
+ Final exam Jan 2013

Provide a reasonable mechanism for the following

transformations.