2622
A. Blanrue, R. Wilhelm
LETTER
Table 2 Cyanosilylation of Aldehydes in CH2Cl2 at Room Temper- aldehydes were tested with the new catalytic system. Hex-
ature with Catalyst 1 (10 Mol%) after 100% Conversion
anal (5l) gave the product 6l in 45% yield after 40 hours
(entry 12, Table 2) and with cyclohexanecarbaldehyde
(5m) the desired product 6m was furnished in 62% yield
after 40 hours (entry 13, Table 2).
Entry Aldehyde
Product Time
(h)
Yield
(%)a
1
2
5a
5b
5c
5d
5e
5f
Benzaldehyde
6a
6b
6c
6d
6e
6f
16
16
16
16
16
15
39
39
16
55
23
40
40
99
82
81
89
83
99
99
65
80
82
96
45
62
In conclusion we have shown that imidazolinium-car-
bodithioate zwitterions are good organocatalysts in the si-
lylcyanation of aldehydes giving the product in very good
yields. The catalysts can be easily recovered. Present
work within the group is investigating the behavior of
asymmetric analogues of the zwitterions as organocata-
lysts.
3-Nitrobenzaldehyde
2-Chlorobenzaldehyde
2,4-Dichlorobenzaldehyde
2,6-Dichlorobenzaldehyde
2-Naphthaldehyde
3
4
5
6
7
5g
5h
5i
1-Naphthaldehyde
6g
6h
6i
General Experimental Procedure
A mixture of 1 mmol of aldehyde, 2 equiv of trimethylsilylcyanide
(0.27 mL) and 10 mol% catalyst in 1 mL CH2Cl2 was stirred under
nitrogen. The reaction was monitored by TLC until all aldehyde was
consumed. After 16–55 h the solvent was evaporated and the crude
product was purified by column chromatography (petrol ether–
EtOAc 9:1) to give the desired compounds as slightly yellow liquids
(yields: 45–99%). As a second fraction the catalyst was isolated as
a deep red crystalline solid (92% yield) after changing the mobile
phase to CH2Cl2.
8
4-Methylbenzaldehyde
2-Methylbenzaldehyde
4-Methoxybenzaldehyde
2-Methoxybenzaldehyde
Hexanal
9
10
11
12
13
5j
6j
5k
5l
6k
6l
5m Cyclohexanecarbaldehyde
6m
a Isolated yields after silica gel chromatography.
Acknowledgment
Financial support by Fonds der Chemischen Industrie, BMBF, DFG
and Nieders. Vorab der Volkswagen Stiftung is gratefully acknow-
ledged.
zwitterion 1 the starting material was all consumed and
the expected product was isolated in 99% yield (entry 1,
Table 1).
The catalyst 2 gave after 16 hours a yield of 11% and 3 a
yield of 53%, yet not all of the aldehyde was consumed
(entries 2 and 3, Table 1). Compound 4 showed no cata-
lytic activity at all (entry 4, Table 1). A blind reaction was
also carried out and as expected no conversion was detect-
ed (entry 5, Table 1). The catalysts were recovered during
flash column chromatography.
References
(1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
John Wiley and Sons: New York, 1994. (b) Jacobsen, E. N.;
Pfaltz, A.; Yamamoto, H. Comprehensive Asymmetric
Catalysis; Springer: Heidelberg, 1999. (c) Schinzer, D.
Selectivities in Lewis Acid Promoted Reactions; Kluwer
Academic Publishers: Dordrecht, 1989.
(2) For a review see: Dalko, P. I.; Moisan, L. Angew. Chem. Int.
Ed. 2001, 40, 3726.
With the found conditions various aldehydes were tested
using catalyst 1. The results are shown in Table 2. Next to
benzaldehyde (5a) the electron deficient benzylic alde-
hydes 5b–f were used and gave after 16 hours the desired
products in good yields between 81% and 99% (entries 2–
6). Even the more sterical hindered 2,6-dichlorobenzalde-
hyde (5e) gave the product 6e in a good yield of 83% (en-
try 5, Table 2). When 1-naphthaldehyde (5g) was applied,
the reaction time increased to 39 hours in order to observe
100% conversion. The product 6g was obtained in an ex-
cellent yield of 99% (entry 7, Table 2). With the electron-
rich benzaldehydes 5i–k good yields between 80% and
96% were also obtained (entries 9–11, Table 2), but the
reaction times needed for total conversion were longer in
the case of 4-methoxybenzaldehyde (5j) with 55 hours
and 2-methoxybenzaldehyde (5k) with 23 hours. 4-Meth-
ylbenzaldehyde (5h) was an exception and gave after a re-
action time of 39 hours only a yield of 65% (entry 8,
Table 2). A repeat of this reaction gave the same result. 2-
Methylbenzaldehyde (5i) yielded 6i in 80% after 16 hours
(entry 9, Table 2). Finally, the reactivities of two aliphatic
(3) For a few recent examples see: (a) List, B.; Lerner, R. A.;
Barbas, C. F. III. J. Am. Chem. Soc. 2000, 122, 2395.
(b) Sakthivel, K.; Notz, W.; Bui, T.; Barbas, C. F. III. J. Am.
Chem. Soc. 2000, 123, 5260. (c) Merino, P.; Tejero, T.
Angew. Chem. Int. Ed. 2004, 43, 2995. (d) Bøgevig, A.;
Poulsen, T. B.; Zhuang, W.; Jørgensen, K. A. Synlett 2004,
1915. (e) Pojarliev, P.; Biller, W. T.; Martin, H. J.; List, B.
Synlett 2004, 1903. (f) Córdova, A. Synlett 2003, 1651. (g)
For a brief review see: Duthaler, R. O. Angew. Chem. Int.
Ed. 2003, 42, 975.
(4) For a few recent examples see: (a) Northrup, A. B.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2002, 124, 2458.
(b) Zhuang, W.; Saaby, S.; Jørgensen, K. A. Angew. Chem.
Int. Ed. 2004, 43, 4476. (c) Cobb, A. J. A.; Shaw, D. M.;
Ley, S. V. Synlett 2004, 558. (d) Ramachary, D. B.;
Chowdari, N. S.; Barbas, C. F. III. Synlett 2004, 1910.
(5) For a few recent examples see: (a) Schuster, T.; Bauch, M.;
Dürner, G.; Göbel, M. W. Org. Lett. 2000, 2, 179. (b) Joly,
G. D.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 4102.
(c) Huang, J.; Unni, A. K.; Thadani, A. N.; Rawal, V. H.
Nature 2003, 424, 146. (d) Braddock, D. C.; MacGilp, I. D.;
Perry, B. G. Synlett 2003, 1121. (e) Iyer, M. S.; Gigstad, K.
M.; Namdev, N. D.; Lipton, M. J. Am. Chem. Soc. 1996, 118,
Synlett 2004, No. 14, 2621–2623 © Thieme Stuttgart · New York