Catalysis
Features include:
Asymmetric Synthesis
Metal and Phosphine
Mediated Transformations
(AtaPhos)2PdCl2, a non-proprietary catalyst for N-Heterocyclic Carbenes
Suzuki-Miyaura cross-coupling reactions
Metal Organic Frameworks
(MOFs)
Catalytic Deprotection with
DEPRO™ Catalyst Kit
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The cover graphic represents the three-dimensional structure of (AtaPhos)2PdCl2, a non-proprietary
catalyst for Suzuki-Miyaura cross-coupling reactions, which has been demonstrated to be broadly All prices are subject to change without notice.
effective in historically challenging couplings. The palladium is represented in red, the phosphines
in yellow, the chlorides in blue, and the nitrogen in green. The hydrogen atoms have been omitted ChemFiles (ISSN 1933–9658) is a publication of
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Asymmetric Synthesis Ph
Asymmetric Synthesis
the bidentate ligand (bis(hydroxamic acid)) would be chelating to the 91%, 97% ee 84%, 97% ee 73%, 95% ee 79%, 95% ee
(0 °C)
metal, this deceleration effect could be resolved. Additionally, it was
hypothesized that a larger R group would prevent the carbonyl oxygen Scheme 1
coordination to the metal by favoring a conformation in which the
carbonyl group was directed towards the cyclohexane (Figure 1). Thus,
Ph
an ideal catalyst system was designed via control of the coordination O
Ph
number as well as the steric environment.
N
O
The use of bis(hydroxamic acid) based ligands in combination with O
V (OiPr)
N
VO(O-iPr)3 proved effective in the efficient asymmetric epoxidation
Ph
of various allylic alcohols (Scheme 1). Using only 1 mol% of the O
Ph
catalyst, Yamamoto and co-workers demonstrated a variety of allylic (1 mol%)
alcohols could be converted to the enantiopure epoxides with excellent OH OH O
OH
TBHP (70% aq), CH2Cl2 +
enantioselectivity. Ph Ph
0 °C Ph
This methodology was also applied in the kinetic resolution of allylic 1 51% conversion
racemic 95% ee 93% ee
alcohol 1, which resulted in high enantioselectivities of the epoxy
alcohol as well as the allylic alcohol (Scheme 2).1 Scheme 2
R = C2H5 R = C2H5
95% ee, 51% yield 95% ee, 48% yield
R = C4H9 R = C4H9
96% ee, 51% yield 96% ee, 48% yield
Scheme 4
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O OH
2 98
SO2 O OH
N
3 92
Ru
N Cl
H2 4 OH
O O OH
(0.5 mol%) CH3
CH3 4 91
IPA, KOH Cl
Cl rt, 19 h
95%, 93% ee
O OH
Scheme 5
5 90
H3CO H3CO
4 (0.4 mol%)
Table 1
N NH
H3CO HCO2H-Et3N (5:2), CH3CN H3CO
CH3 28 °C, 3 h CH3
>99%, 95% ee
Scheme 6
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(1R,2R)-N,N′-Dihydroxy-N,N′-bis(diphenylacetyl)-1,2- 8 (1R,2R)-N,N′-Dihydroxy-N,N′-bis(3,3,3-triphenyl- 8
cyclohexanediamine, 97% propionyl)-1,2-cyclohexanediamine, 95%
(1R,2R)-N,N′-Dihydroxy-N,N′-bis(diphenylacetyl)-cyclo Ph (1R,2R)-N,N′-Dihydroxy-N,N′-bis(triphenylpropionyl)- O
Ph
Ph
hexane-1,2-diamine; (R)-CBHA-DPA; (1R,2R)-N,N′-1,2-cyclo O
Ph
cyclohexane-1,2-diamine; N,N′-(1R,2R)-1,2-cyclohexane Ph
N
hexanediylbis[N-hydroxy-α-phenyl-benzeneacetamide] N diylbis[N-hydroxy-β,β-diphenylbenzenepropanamide]; OH
OH OH
[860036‑16‑4] OH
(R)-CBHA-TPP N Ph
N
C34H34N2O4 [860036‑29‑9] O
Ph
Ph Ph
FW 534.64 O C48H46N2O4
Ph
FW 714.89
mp.................................................................................. 200 to 205 °C mp.................................................................................. 217 to 221 °C
[α] 22
D +90.0°, c = 1 in chloroform
D +14.0°, c = 1 in chloroform
[α] 22
700592-50MG 50 mg 700541-50MG 50 mg
(1S,2S)-N,N′-Dihydroxy-N,N′-bis(diphenylacetyl)-
Asymmetric Synthesis
8 (1S,2S)-N,N′-Dihydroxy-N,N′-bis(3,3,3-triphenyl- 8
1,2-cyclohexanediamine, 97% propionyl)-1,2-cyclohexanediamine, 95%
(1S,2S)-N,N′-Dihydroxy-N,N′-bis(diphenylacetyl)-cyclo Ph
(1S,2S)-N,N′-Dihydroxy-N,N′-bis(triphenylpropionyl)- Ph
O O
hexane-1,2-diamine; (S)-CBHA-DPA; (1S,2S)-N,N′-1,2-cyclo Ph cyclohexane-1,2-diamine; (S)-CBHA-TPP; N,N′-(1S,2S)- Ph
N Ph
hexanediylbis[N-hydroxy-α-phenyl-benzeneacetamide] N
OH 1,2-cyclohexanediylbis[N-hydroxy-β,β-diphenylbenzene OH
C34H34N2O4 OH propanamide] N
OH
Ph
N
FW 534.64 Ph C48H46N2O4 Ph
O O
Ph
Ph FW 714.89
mp.................................................................................. 217 to 221 °C
mp.................................................................................. 199 to 204 °C
[α] 22
D −14.0°, c = 1 in chloroform
D -79.0°, c = 1 in chloroform
[α] 22
700533-50MG 50 mg
700576-50MG 50 mg
Vanadium(V) oxytriisopropoxide
(1R,2R)-N,N′-Dihydroxy-N,N′-bis(bis(3,5-dimethyl- 8
phenyl)acetyl)-1,2-cyclohexanediamine, 97% Triisopropoxyvanadium(V) oxide; Vanadium(V) trisiso CH3
O
CH3
[α] 22
D +76.0°, c = 1 in chloroform tert-Butyl hydroperoxide solution
700584-50MG 50 mg
TBHP H3C O
OH
[75‑91‑2] H3C CH3
(1S,2S)-N,N′-Dihydroxy-N,N′-bis(bis(3,5-dimethylphenyl) 8
Merck 13,1569; Beil. 1,IV,1616
acetyl)-1,2-cyclohexanediamine, 97%
C4H10O2
(1S,2S)-N,N′-Dihydroxy-N,N′-bis(3,5-dimethyl H3C CH3
FW 90.12
diphenylacetyl)-cyclohexane-diamine; 5.0-6.0 M in nonane
(S)-CBHA-DMDA; N,N′-(1S,2S)-1,2-cyclo CH3
O water.............................................................................................<4%
hexanediylbis[α-(3,5-dimethylphenyl)-N-hydroxy-
3,5-dimethylbenzeneacetamide] N density......................................................................0.817 g/mL, 25 °C
OH
CH3
C42H50N2O4 CH3 n 20 ............................................................................................. 1.399
OH D
FW 646.86 N
418064-50ML 50 mL
O CH3
Cumene hydroperoxide, 80%
α,α-Dimethylbenzyl hydroperoxide H3C CH3
H3C CH3 OH
[80‑15‑9] O
mp.................................................................................. 186 to 190 °C Beil. 6,IV,3221
[α] 22
D −76°, c = 1 in chloroform
C9H12O2
700568-50MG 50 mg
FW 152.19
bp........................................................................100-101 °C/8 mmHg
vd......................................................................................... 5.4 (vs air)
vp.........................................................................<0.03 mmHg (20 °C)
technical grade
density........................................................................1.03 g/mL, 25 °C
n 20
D ........................................................................................... 1.5210
247502-5G 5 g
247502-100G 100 g
247502-500G 500 g
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product synthesis. Olsson et al. reported the use of a palladium 40-60 °C, 16-24 h
pincer complex in combination with diboronic acid for the boronation KHF2
of readily available allylic alcohols. Under mild conditions, a variety
of allylic alcohols were reacted with 5 mol% catalyst to yield the
R BF3K
corresponding boronic acids, which were converted to the more
stable trifluoroborate salt derivatives in good yields. Considering the O
widely available nature of allylic alcohols, the mildness of the reaction
Scheme 2
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FW 258.04 Cl
Di-μ-chlorobis[(1,2,5,6-η)-1,5-cyclooctadiene]
Cl
dirhodium; Bis(1,5-cyclooctadiene)dirhodium(I) Rh Rh
dichloride; 1,5-Cyclooctadienerhodium(I) Cl
chloride dimer; Rhodium(I) chloride
1,5-Cyclooctadiene complex dimer
[12092‑47‑6]
C16H24Cl2Rh2
FW 493.08
mp.................................................................................... 243 °C (dec.)
227951-500MG 500 mg
227951-5G 5 g
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1,3,5-Triaza-7-phosphaadamantane, 97% 8
1,3,5-Triaza-7-phosphatricyclo[3.3.1.13.7]decane; PTA; NSC N
266642 N N
[53597‑69‑6] P
C6H12N3P
FW 157.15
mp.................................................................................. 244 to 250 °C
695467-500MG 500 mg
695467-2G 2 g
CH3
Hydroformylation P
Ph
H3C O
Despite a long-standing belief that formyl groups cannot be generated O CH3
O
at quaternary carbon centers via hydroformylation, Clarke and Roff CH3
CHO
(1 mol%)
have developed a method utilizing 1,3,5,7-tetramethyl-6-phenyl-2,4,8- NC(H2C)2 CO2Me NC(H2C)2 CO2Me
[Rh(acac)(CO)2] (0.2%)
trioxa-6-phosphaadamantane, an air-stable phosphane ligand, which 50 °C, 50 bar, 70 h
inhibited hydrogenation and provided excellent levels of regioselectivity Scheme 5
(for quaternary versus linear regioisomer) (Scheme 5).4
References: (1) Olsson, V. J. et al. J. Am. Chem. Soc. 2006, 128, 4588. (2) Lewis, J. C. et al.
J. Am. Chem. Soc. 2008, 130, 2493. (3) He, Z. et al. Adv. Synth. Catal. 2006, 348, 413. (4)
Clarke, M. L.; Roff, G. J. Chem.-Eur. J. 2006, 12, 7978.
1,3,5,7-Tetramethyl-6-phenyl-2,4,8-trioxa-6- 8
phosphaadamante, 97%
me
CgPPh; 1,3,5,7-Tetramethyl-8-phenyl-2,4,6- CH3
Ph
trioxa-8-phosphatricyclo[3.3.1.13,7]decane P
O
[97739‑46‑3] H3C
O CH3
C16H21O3P O
CH3
FW 292.31
mp.................................................................................. 106 to 111 °C
695459-100MG 100 mg
695459-500MG 500 mg
695459-2G 2 g
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BRIDP Catalysts O O
Researchers at Takasago developed two phosphine-based ligands
O
for the Buchwald-Hartwig amination reaction with successful results 2 Br
O
for the cross-coupling of a wide array of amines and aryl halides. N 91
These ligands exhibit several noteworthy advantages, with regard to
efficiency and turnover numbers, as well as the ability to access biaryls
substituted with a nitrogen atom. H3C
2 Cl N 94a
Cl
P
N N
(10 mol%) H
3 Cl N CH3 95a
Pd(dba)2 (5 mol%) N
Cl + NH2 1
R R2
R1 R2 NaOtBu, toluene, 105 °C
a
H OMe H H xylene in place of toluene, 120 °C, 3 h
N N N
Table 3
97% 93% 87%
Scheme 6
CH3
P
CH3
Cl (2 mol%) N
P
[(π-allyl)PdCl]2 (0.5 mol%)
Cl + 3 eq N H N
NaO-t-Bu, xylene
Cl N
120 °C, 3 h
(4 mol%)
Pd(OAc)2 (1 mol%)
NH + Br N
NaO-t-Bu, toluene
100 °C, 3 h 67%
97%
Scheme 7
Scheme 8
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2-Chloro-1,3-bis(2,6-diisopropylphenyl)-1,3,2-diaza- 8 Cy-vBRIDP 8
phospholidine Dicyclohexyl(1-methyl-2,2-diphenylvinyl)
[314730‑65‑9] i-Pr i-Pr phosphine; 2-(Dicyclohexylphosphino)-1,1- CH3
C26H38ClN2P N N
diphenyl-1-propene
P
FW 445.02 P [384842‑24‑4]
Cl i-Pr
i-Pr C27H35P
mp.................................................................................. 212 to 220 °C FW 390.54
694207-250MG 250 mg
mp.................................................................................. 124 to 130 °C
694207-1G 1 g 702943-100MG 100 mg
702943-500MG 500 mg
Cy-cBRIDP 8
1-(Dicyclohexylphosphino)-2,2-Diphenyl-
1-methylcyclopropane; Dicyclohexyl(2,2- CH3
702951-100MG 100 mg
702951-500MG 500 mg
Hartwig and co-workers have reported the use of the electron-rich [84680‑95‑5] t-Bu
C26H44FeP2 P
and bulky ligand 1,1’-bis(di-tert-butylphosphino)ferrocene for the t-Bu
Fe
amination of aryl halides and for the first amination of aryl tosylates. FW 474.42 t-Bu
P
The amination of various amines with aryl chlorides, iodides, and t-Bu
tosylates was effected using this novel ligand in combination with a
mp...................................................................................... 73 to 75 °C
palladium source affording the coupled products in excellent yield.
This ligand is exceptionally effective and, though the electron density 695149-250MG 250 mg
on the metal helps accelerate the oxidative addition (a necessity for 695149-1G 1 g
unactivated aryl chlorides), the electron-richness does not negatively
1,1′-Bis(di-tert-butylphosphino)ferrocene palladium 8
impact the reductive elimination since the steric bulk associated with
this ligand facilitates this last step of the catalytic cycle (Table 4).7 dichloride, 98%
References: (5) Ackermann, L. et al. Angew. Chem., Int. Ed. 2006, 45, 7627. (6) (a) Suzuki,
[95408‑45‑0] t-Bu t-Bu
P
K. et al. Adv. Synth. Catal. 2007, 349, 2089. (b) Suzuki, K. et al. Adv. Synth. Catal. 2008, C26H44Cl2FeP2Pd Cl
350, 652. (7) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 7369. FW 651.75 Fe Pd
Cl
P
t-Bu
t-Bu
702005-250MG 250 mg
Cl H
N 702005-1G 1 g
NH2Bu Bu 1 mol% Pd(dba)
3 57
110 °C, 24h
CH3 CH3 1,1′-Bis(di-cyclohexylphosphino)ferrocene palladium 8
dichloride, 98%
4 NH2Ph NC NC 79
2 mol% Pd(dba)2 [917511‑90‑1]
OTs N Ph 110 °C, 16h
H C34H52Cl2FeP2Pd
FW 755.90 P
Cl
CH3 CH3 Pd
1 mol% Pd(dba)2 Fe
NH2Bu Bu Cl
5 49
H3C I H3C NH rt, 7h P
Table 4
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References: (8) Gonzalez-Bobes, F.; Fu, G. C. J. Am. Chem. Soc. 2006, 128, 5360. (9) (a) H3C
Singer, R. A. et al. Tetrahedron Lett. 2006, 47, 3727. (b) Singer, R. A. et al. Synthesis 2003,
7 Cl N 99
1727. (c) Guram, A. S. et al. Org. Lett. 2006, 8, 1787.
N
H3CS H3C
H3CO
NiCl2 •glyme (6 mol%)
Ralkyl Cl + (HO)2B R1 Ralkyl R1 8 Cl N OCH3 98
prolinol (12 mol%) N
KHMDS (2 equiv) H3CO
i-PrOH, 60 °C
1 Cl B(OH)2 80
10 Cl CH3 96
S
Cl
2 Me H3C B(OH)2 74
Me
CH3
N
11 Br OCH3 93
Cl N
3 F B(OH)2 46a H3C
CH3
OTBS
CH3
4 O Cl F3 C B(OH)2 79 N
12 Br F 95
N
H3C
aYield of trans isomer CH3
Table 5 Table 6
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Visit sigma-aldrich.com/chirosolv
ChiroSolv Resolving Kits for ChiroSolv Resolving Kits for
for more information.
Liquid Racemates Solid Racemates
681431 Acid Series 1 698881 Acid Series 1
681423 Acid Series 2 699527 Acid Series 2
681415 Acid Series 3 698873 Acid Series 3
699217 Acid Series 4 699225 Acid Series 4
681407 Base Series 1 699233 Base Series 1
681393 Base Series 2 698938 Base Series 2
681377 Base Series 3 698946 Base Series 3
699241 Base Series 4 698954 Base Series 4
sigma-aldrich.com
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Gold Catalysis
The Friedel-Crafts reaction is well-documented in organic chemistry;
however, one major limitation is the common use of strong acids.
There have been studies on the use of stoichiometric and catalytic metals O O
P
to accelerate this important class of reactions. Since gold catalysts can O
Au Cl
be considered as metallic sources of H+, several research groups have MeO2C CO2Me MeO2C CO2Me
successfully demonstrated the utility of Au(I) catalysts for Friedel-Crafts-
(3-10 mol%)
type reactions. Tarselli and Gagne recently reported an efficient and
functional-group-tolerant method for the cyclization of 4-allenyl arenes AgSbF6 (5 mol%) R
0.2M CH2Cl2
to afford benzocycles in the presence of chloro(triphenylphosphite) R
6-16 h
gold. The reaction was generally amenable with electron-rich arenes,
CO2Me CO2Me
but heterocyclic aromatic compounds with coordinating abilities such as CO2Me
MeO2C MeO2C
MeO2C CO2Me
MeO2C
triazoles, isoxazoles, and oxazoles led to catalyst poisoning. On the other
Metal and Phosphine Mediated Transformations
MeO
hand, the reaction was tolerant of functional groups and moieties such N
as ethers, acetals, and pyrroles (Scheme 9).10 MeO O
OMe O
Echavarren and co-workers used a Au(I) catalyst to effect the
transformation of substrate 4 to 5. This reaction proceeds through a 79% 59% 93% 87%
Scheme 10
t-Bu
t-Bu t-Bu
O O
P
t-Bu AuCl
O
t-Bu
t-Bu
6
Z + NuH (5 mol%) Z
R2
1 AgSbF6 (5 mol%) R1
R
CH2Cl2 H Nu
R2
T (°C),
entry enyne NuH product % yield
time (h)
NC
NC
1 Z = NTs, R1=Ph, R2 = H 23, 48 49
N Z NH
H
H Ph
MeO
MeO
2 1 2 -50, 5 63
Z = C(CO2Me)2, R = R = Me
N Z NH
H
H
OMe H
OMe
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(Acetonitrile)[(2-biphenyl)di-tert-butylphosphine] 8 Bis(3,5-dimethylphenyl)chlorophosphine 8
gold(I) hexafluoroantimonate [74289‑57‑9] Cl
density......................................................................1.102 g/mL, 25 °C
mp.............................................................................198 to 203 °C (D) n 20
D ............................................................................................. 1.606
Chloro[tris(2,4-di-tert-butylphenyl)phosphite]gold 8
[Tris(2,4-di-tert-butylphenyl)phosphite]gold t-Bu
chloride
New Ligands
[915299‑24‑0] t-Bu t-Bu Di-tert-butylcyclohexylphosphine, 95% 8
C42H63AuClO3P O O
P [436865‑11‑1] H3C
FW 879.34 Au Cl H3C CH3
t-Bu
O C14H29P
P CH3
t-Bu
FW 228.35
H3C CH3
t-Bu
Dicyclohexyl-(2,6-diisopropylphenyl)phosphine, 97% 8
New Phosphine Precursors C24H39P
Bis(3,5-di-tert-butyl-4-methoxyphenyl)phosphine 8
FW 358.54 i-Pr i-Pr
P
C30H47O2P t-Bu
H
P t-Bu
FW 470.67
H3CO OCH3 mp.................................................................................... 96 to 100 °C
t-Bu t-Bu
698814-250MG 250 mg
mp.................................................................................. 114 to 119 °C
698814-1G 1 g
kanata purity
Triisopropylphosphonium tetrafluoroborate, 97% 8
694673-100MG 100 mg [121099‑07‑8] H3C CH3
694673-500MG 500 mg C9H22BF4P H
H3C P CH3 BF4-
Bis(3,5-di(trifluoromethyl)phenyl)phosphine 8 FW 248.05 CH3 CH3
[166172‑69‑6] F3C
H
P CF3 698466-500MG 500 mg
C16H7F12P
FW 458.18 2-(2-(Diphenylphosphino)ethyl)pyridine 8
CF3 CF3 [10150‑27‑3]
mp...................................................................................... 69 to 73 °C C19H18NP N P
Ph
FW 291.33 Ph
kanata purity
mp...................................................................................... 58 to 62 °C
695335-100MG 100 mg
695335-500MG 500 mg kanata purity
695599-100MG 100 mg
Bis(3,5-di(trifluoromethyl)phenyl)chlorophosphine 8
695599-500MG 500 mg
[142421‑57‑6] Cl
C16H6ClF12P F3C P CF3
FW 492.63
CF3 CF3
New Palladium Complexes
mp...................................................................................... 25 to 29 °C (1,3-Bis(diphenylphosphino)propane)palladium(II) 8
kanata purity chloride
Dichloro[1,3-bis(diphenylphosphino)propane] Ph
694746-100MG 100 mg P Ph
palladium(II)
694746-500MG 500 mg Pd Cl
[59831‑02‑6] P
Ph Ph Cl
C27H26Cl2P2Pd
FW 589.77
696676-500MG 500 mg
696676-2G 2 g
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N-Heterocyclic Carbenes
Enyne Cyclizations
Echavarren and co-workers have also demonstrated the utility of
Au-NHCs in the reactions of 1,6-enynes. They determined that
the outcome of the cyclization of 1,6-enyne 1 (Scheme 1) was
dependent on the ligand coordinated to the metal. When 2 was used N N
SnBu3
R1
R1 + N2 CO2R R1 R2
N N +
+ N2 CO2Et PhI NTs
Au
Cl Ts
2 CO2R CO2Et N
(5 mol%) SnBu3 R2
O O R1
COPh R1 R1
COPh
TsN TsN
Ph Ph
TsN COPh COPh
Ph AgSbF6 (5 mol%) +
Ph
1 CH2Cl2, 0.5 h
H
H Ph Scheme 4
99% (98:2)
Scheme 1
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Nolan and co-workers have described the use of the Cu-Imes carbene
complex 5 in the olefination of aldehydes (and ketones) in the
N N
presence of PPh3, i-PrOH, and TMSCHN2. While similar olefinations
have been reported using Wilkinson’s catalyst, the Cu-alternative offers Cu
Cl
a more economical solution. The functional group compatibility is quite 5
good, allowing for the formation of functionalized aliphatic olefins, (5 mol%)
O
dienes, and styrenes containing nitro (notoriously deleterious to these TMSCHN2 (1.4 eq)
N-Heterocyclic Carbenes
Org. Lett. 2007, 9, 2653. (3) (a) Díez-González, S. et al. Organometallics, 2006, 25, 2355.
(b) Díez-González, S.; Nolan, S. P. Acc. Chem. Res. 2008, 41, 349. (c) Jurkauskas, V. et al. Boc
N
Org. Lett. 2003, 5, 2417. (d) Lebel, H. et al. J. Org. Chem. 2007, 72, 144. (e) Trost, B. M.;
Dong, G. J. Am. Chem. Soc. 2006, 128, 6054. (f) Fructos, M. R. et al. J. Am. Chem. Soc.
2004, 126, 10846. (g) Kaur H. et al. Organometallics 2004, 23, 1157. (h) Díez-González,
74% 88%
S.; Nolan, S. P. Aldrichimica Acta 2008, 41, 43. (4) Lebel, H. et al. J. Org. Chem. 2007,
72, 144.
Scheme 5
i-Pr i-Pr
1,3-Bis(2,4,6-trimethylphenyl)imidazol-2-ylidene gold(I) 8
N N
chloride, 95%
Cu
Chloro[1,3-bis(2,4,6-trimethylphenyl)imidazol- CH3 H3C i-Pr
Cl
i-Pr
mp............................................................................................. 298 °C
696277-100MG 100 mg
696277-500MG 500 mg
[1,3-Bis(2,6-diisopropylphenyl)imidazol-2-ylidene] 8
copper(I) chloride
[578743‑87‑0] i-Pr
C27H36ClCuN2
N
FW 487.59 i-Pr
N CuCl
i-Pr i-Pr
mp........................................................................................... >300 °C
696307-250MG 250 mg
696307-1G 1 g
Bis[1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene] 8
copper(I) tetrafluoroborate
C42H48BCuF4N4 CH3 CH3
FW 759.21
CH3
H3C H3C CH3
N N
Cu BF4-
N N
H3C CH3 CH3
H3C
CH3 CH3
696242-250MG 250 mg
696242-1G 1 g
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com. 17
$
696250-100MG 100 mg
tetrafluoroborate, 95%
696250-500MG 500 mg SIMes-HBF4; 4,5-Dihydro-1,3-bis(2,4,6-trimethylphenyl)- CH3
1H-imidazolium tetrafluoroborate(1-); 4,5-Dihydro- H3C
N-Heterocyclic Carbenes
[244187‑81‑3] C27H39BF4N2
N
C27H36N2 i-Pr FW 478.42
FW 388.59 N
mp................................................................................................ >300
i-Pr i-Pr
693553-1G 1 g
693553-5G 5 g
mp.................................................................................. 213 to 217 °C
696196-250MG 250 mg
1,3-Di-tert-butylimidazolinium tetrafluoroborate, 95%
696196-1G 1 g 1,3-Bis(tert-butyl)-4,5-dihydro-1H-imidazolium tetrafluoro t-Bu
N+
borate; N,N′-Bis(tert-butyl)dihydroimidazolium tetrafluoro BF4-
1,3-Dicyclohexylimidazolium tetrafluoroborate salt, 97% borate N
t-Bu
[286014‑38‑8] [137581‑21‑6]
C15H25BF4N2 C11H23N2 · BF4
FW 320.18 N FW 270.12
N BF4- 659991-1G 1 g
659991-5G 5 g
18 sigma-aldrich.com TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit sigma-aldrich.com/chemicalsynthesis.
$
Metal Organic Frameworks (MOFs) ZIF-8 (sold by Aldrich under the name Basolite™ Z1200, 691348) and
ZIF-69, which is useful for CO2 storage.8 The high thermal stability
Stephen Caskey, Ph.D. of ZIFs points to the potential for application as solid supports for
Scientist, New Product Research catalysis. Several MOFs have already been examined as solid supports,
Sigma-Aldrich Corporation analogous to alumina, silica, or activated carbon, for heterogeneous
catalysts to improve surface areas and enhance recyclability. Férey and
Metal-organic frameworks (MOFs) are a relatively new class of porous,
co-workers recently reported the preparation of Pd-impregrenated MIL-
crystalline materials with a broad range of applications. MOFs are
101, a Cr-based MOF, that showed good activity and recyclability for
composed of metal ions or clusters, which act as the joints, bound
the Heck reaction of iodobenzene with acrylic acid (Scheme 3).9
by multidirectional organic ligands, which act as linkers in the
network structure. These networks can be 1-D, 2-D, or 3-D extended, References: (1) Chui, S. S.-Y. et al. Science 1999, 283, 1148. (2) Wong-Foy, A. G. et al.
periodic structures. The joints and linkers assemble in such a way that J. Am. Chem. Soc. 2006, 128, 3494. (3) (a) Alaerts, L. et al. Angew. Chem., Int. Ed. 2007,
regular arrays are formed resulting in robust (often porous) materials 46, 4293. (b) Alaerts, L. et al. J. Am. Chem. Soc. 2008, 130, 14170. (c) Finsy, V. et al.
J. Am. Chem. Soc. 2008, 130, 7110. (4) Horike, S. et al. J. Am. Chem. Soc. 2008, 130,
analogous to zeolites. MOFs are the highest reported surface area 5854. (5) Ritter, S. Chem. Eng. News 2008, 86(16), 8. (6) Schlichte, K. et al. Microporous
C300, 688614).6
Scheme 2
ZIFs
O Pd on MOF O
New MOF materials termed zeolitic imidazolate frameworks (ZIFs) I +
OH DMA
are generated from metal ions and imidazolate anions.7 The bonding 120 °C OH
angles of the imidazolate are thought to mimic the bonding angles 5h ≥ 95% conversion
about Si-O bonds found in zeolites; thus, ZIFs and zeolites tend to Scheme 3
form closely related structures. ZIFs involve M-N bonds instead of M-O
bonds. The thermal stability of ZIFs are reported to be higher than
most MOFs, up to ca. 500 ºC, however, organic components are still
present, which limit the stability. Some of the most important ZIFs are
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com. 19
$
C8H5AlO5 [554‑95‑0]
FW 208.10 Beil. 9,IV,3747 O O
C9H6O6
bulk density............................................................................0.4 g/cm3 OH OH
FW 210.14
BET surf. area.............................................................. 1100-1500 m2/g mp........................................................................................... >300 °C
particle size distribution................................................31.55 μm (D50) acetic acid.....................................................................................<5%
688738-10G 10 g
482749-100G 100 g
688738-100G 100 g
482749-500G 500 g
688738-500G 500 g
Terephthalic acid, 98%
Basolite™ C 300 8
Benzene-1,4-dicarboxylic acid O
Metal Organic Frameworks (MOFs)
C8H12N4Zn Beil. 9,921 OH
FW 229.60 C12H8O4 HO
FW 216.19 O
bulk density..........................................................................0.35 g/cm3
mp........................................................................................... >300 °C
BET surf. area.............................................................. 1300-1800 m2/g
particle size.......................................................................4.9 μm (D50) 523763-5G 5 g
1,3,5-Tris(4-carboxyphenyl)benzene, ≥98% 8
690872-10G 10 g
690872-100G 100 g 4,4′,4′′,-Benzene-1,3,5-triyl-tris(benzoic acid) O OH
C3H4N2 O O
FW 68.08 mp.................................................................................. 322 to 327 °C
pKa (25 °C)................................................................................... 6.95 solvent ≤20 wt. %
mp...................................................................................... 88 to 91 °C
686859-1G 1 g
bp............................................................................................. 256 °C
vp..............................................................................<1 mmHg (20 °C)
2-Methylimidazole, 99%
2-Methylglyoxaline N
ReagentPlus® [693‑98‑1] CH3
N
H
I202-1G 1 g Beil. 23,V,5,35
I202-5G 5 g C4H6N2
I202-100G 100 g FW 82.10
I202-500G 500 g mp.................................................................................. 142 to 143 °C
I202-2KG 2 kg bp...................................................................................... 267-268 °C
vp................................................................................<1 mmHg (0 °C)
M50850-100G 100 g
M50850-500G 500 g
20 sigma-aldrich.com TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit sigma-aldrich.com/chemicalsynthesis.
$
Catalytic Deprotection—DEPRO™
Catalyst Kit/Catalytic Deprotection N-debenzylation with L-(-)-N-Benzyl-α-methylbenzylamine
H2 Uptake (ml)
100
In the manufacture of pharmaceuticals and fine chemicals there is
often a requirement for a protection strategy to minimize possible 80
side reactions during a synthesis. Small, easily removed protecting
groups (PG), available for a range of functional groups, is highly 60
desired. One such easily removed PG is derived from the facile catalytic
40
Model Reactions
Two model reactions were selected and investigated; the debenzylation
of 2,3,4,6-tetra-O-benzyl-D-glucopyranose, and the debenzylation of
N-benzyl N-α-methylbenzylamine.
Sigma-Aldrich’s ChemBlogs
Standard reaction conditions for deprotection of the glucopyranose
sugar were 25oC, 3 bar hydrogen pressure using a 5 weight percent An industry-first for open scientific discussion.
catalyst loading based on substrate (for 5% Pd/C catalysts). Standard
reaction conditions for deprotection of the amine were 50oC, 3 bar
hydrogen pressure with a 5 weight percent catalyst loading based on
substrate (for 5% Pd/C catalysts). Catalysts with higher percent metal
loadings were evaluated on an equal metal basis. Screening reactions
were carried out in an Argonaut Endeavor™ 8 x 10 ml reactor system.
Reactions, products and byproducts were monitored by hydrogen
uptake, GC and/or HPLC.
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com. 21
$
Solvent Effects
Solvent choice is critical for any deprotection reaction. For amine Hydrogenation of N-Benzyl-N-α-methylbenzylamine at 50°C,
deprotection, the free amine products are well known to strongly 3 bar hydrogen pressure with various catalysts in ethanol
adsorb at active sites, inhibiting or even completely poisoning the 45
catalyst. For each of the O-debenzylation and N-debenzylation
reactions a series of commonly employed solvents, THF, ethanol, 40
ethyl acetate, acetic acid, and solvent mixtures were screened under 35
H2 Uptake (mL)
standard reaction conditions using several of the top performing 30
catalysts. Results were in general independent of specific catalyst type.
25
For the O-debenzylation, reaction rates were fastest in THF, slightly
20
slower in ethanol and acetic acid, and slowest in ethyl acetate.
Reaction rates were generally linear with all reactions ultimately 15
producing the completely debenzylated product.
Catalytic Deprotection—DEPRO™ Catalyst Kit/Catalytic Deprotection
10
For the N-debenzylation, reaction rates were fastest in ethanol and 5
slowest in THF (Figure 2). The presence of acid served to prevent 0
catalyst inhibition through protonation of the amine product. 0 30 60 90 120 150 180
Time (min)
Catalyst Design Effects
DEPRO-901 DEPRO-904 DEPRO-905 DEPRO-903
The performance of a Pd/C catalyst is affected by the nature of the DEPRO-906 DEPRO-902 Pearlman's
underlying carbon support, the size and location of the deposited
metal particulates, the active metal precursor, the metal oxidation
Figure 2
state and the method of catalyst preparation. Metal particulates can
be made to distribute preferentially at the exterior surface of the
support (an eggshell or surface loaded catalyst) or be evenly dispersed Deprotection kit I for N-O debenzylation 8
throughout the support structure (a standard or uniform catalyst).
Deposited metal may be either in a reduced or unreduced form. Deprotection kit I for N-O debenzylation
22 sigma-aldrich.com TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit sigma-aldrich.com/chemicalsynthesis.
PTS Amphiphile for Metathesis and
Cross-Coupling in Water
Recently introduced by Professor Bruce Lipshutz of the reaction mixture with EtOAc-hexane or deposition
UC-Santa Barbara, polyoxyethanyl α-tocopheryl sebacate onto a bed of silica gel and elution with EtOAc. In most
(PTS) is a nonionic amphiphile that is proving to be a examples studied, PTS outperformed other non-ionic
versatile “solubilizer” for organic molecules in water.1 amphiphiles such as Triton®-X100 and Brij® 30.
Lipophilic substrates and catalysts can efficiently enter
the micelles formed by PTS in water leading to important O
cross-coupling reactions at room temperature without the O O
H
O
need for a co-solvent. O
4 n
O
To use, one simply places the requisite amount of PTS
(15 wt% in water) into a test tube with a stir bar and PTS (n = ca. 13)
adds the organic substrate(s) and catalyst. Reactions 698717
are generally complete within 3–24 hours and can be
accelerated if needed upon mild heating to 40–50 °C.
Work-up is also very simple involving either extraction of
Sonogashira Coupling6
References: (1) Sold under license from Zymes, LLC. (2) Lipshutz, B. H. et al. Org. Lett. 2008, 10, 1325. (3) Lipshutz, B. H. et al. Adv. Synth. Catal. 2008, 350, 953. (4) (a) Lipshutz, B. H. et al. Org. Lett.
2008, 10, 1333. (b) Lipshutz, B. H.; Abela, A. R. Org. Lett. 2008, 10, 5329. (5) (a) Lipshutz, B. H.; Taft, B. R. Org. Lett. 2008, 10, 1329. (b) Neither acrylates nor styrenes any longer require 15 wt% PTS/
water in coupling to aryl iodides; see Lipshutz, B. H.; Ghorai, S. Aldrichimica Acta, 2008, 41, 59. (6) Lipshutz, B. H. et al. Org. Lett. 2008, 10, 3793.
Triton® and Brij® are registered trademarks of ICI Americas, Inc. and Union Carbide Corporation, respectively.
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and its affiliate Sigma-Aldrich Biotechnology, L.P. Sigma brand products are sold through Sigma-Aldrich, Inc. Sigma-Aldrich, Inc. warrants that its products conform to the information
contained in this and other Sigma-Aldrich publications. Purchaser must determine the suitability of the product(s) for their particular use. Additional terms and conditions may apply.
Please see reverse side of the invoice or packing slip. Eppendorf® is a registered trademark of Eppendorf-Netheler-Hinz GmbH. Sepharose® is a registered trademark of GE Healthcare.
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