rate of each diastereomer with a reducing agent (dynamic
kinetic resolution). In contrast, reduction of R-alkylated
â-ketosulfoxides under similar basic conditions shows
only low stereoselectivity.3 There is no report on the
reduction of R-alkylated â-ketosulfoxides with DIBAL
through a dynamic kinetic resolution pathway. Recently,
we have reported reactions of the R-sulfinyl carbanion
of â-(trimethylsilyl)ethyl sulfoxide as a powerful chiral
inducer,6,7 in which Si-O interaction in the transition
state has been demonstrated. We now report a highly
stereoselective reduction of R-(trimethylsilyl)methyl-â-
ketosulfoxides that proceeds through a dynamic kinetic
resolution pathway, involving a transition state stabilized
by the Si-O interaction.
We examined the reaction of the R-sulfinyl carbanion,
derived from p-tolyl â-(trimethylsilyl)ethyl sulfoxide 1,6a
with various esters and subsequent in situ reduction of
the produced R-(trimethylsilyl)methyl-â-ketosulfoxides 4
with various reducing agents. We also studied a similar
reaction of R-alkyl p-tolyl sulfoxides 2 and 3. The results
are summarized in Table 1.
Asym m etr ic Red u ction of
r-(Tr im eth ylsilyl)m eth yl-â-k etosu lfoxid e
w ith DIBAL u n d er Ba sic Con d ition s
Shuichi Nakamura, J un-ichi Nakayama, and
Takeshi Toru*
Department of Applied Chemistry, Nagoya Institute of
Technology, Gokiso, Showa-ku, Nagoya, 466-8555, J apan
toru@ach.nitech.ac.jp
Received March 5, 2003
Abstr a ct: The reaction of the R-carbanion of p-tolyl 2-(tri-
methylsilyl)ethyl sulfoxide with esters followed by reduction
with DIBAL gave R-(trimethylsilyl)methyl-â-hydroxysulfox-
ides with high stereoselectivity. The stereoselective reaction
was demonstrated to proceed through a dynamic kinetic
resolution pathway via a six-membered cyclic transition
state involving Si-O interaction. These reactions provide a
convenient route for the synthesis of optically pure allylic
alcohols.
A THF solution of â-(trimethylsilyl)ethyl sulfoxide 1
was treated with LDA (1.3 equiv)8 at -78 °C and
subsequently reacted with ethyl benzoate (1.5 equiv),
forming â-ketosulfoxide 4a . Without isolation of 4a ,
DIBAL (1.6 equiv) was added to this solution at -78 °C.
A single diastereomer 5a A out of four possible diaster-
eomeric â-hydroxysulfoxides 5a shown in Scheme 1 was
formed in 60% yield.9 The unreduced â-ketosulfoxide 4a
was isolated in 38% yield in a syn/anti ratio of 79:21
(entry 1). On the other hand, the one-pot reduction of 4a
with other reducing agents such as LiAlH4, L-selectride,
and NaBH4 gave two diastereomeric products 5a A and
5a B but with low stereoselectivities (entries 2-4). The
reaction of 1 with other esters and subsequent reduction
with DIBAL also gave â-hydroxysulfoxides 5bA-d A as
single diastereomers together with unreduced â-ketosul-
foxides 4b-d (entries 5-7). In contrast to the highly
stereochemical outcome in the reduction of R-(trimeth-
ylsilyl)methyl-â-ketosulfoxides 4a-d, reduction of R-alkyl-
â-ketosulfoxides 4e and 4f with DIBAL showed low
stereoselectivity on the carbon R to the sulfinyl group
giving the diastereomeric products 5e and 5f in an A/C
ratio of 74:26 and 72:28, respectively (entries 8 and 9).11
It is well-known that reduction of â-ketosulfoxides with
diisobutylaluminum hydride (DIBAL) gives â-hydrox-
ysulfoxides with high diastereoselectivity.1 The DIBAL
reduction of a diastereomeric mixture of R-substituted
â-ketosulfoxides, which possibly affords four diastereo-
meric isomers, shows high selectivity with respect to
carbonyl face selection, but the products are generally
obtained as an inseparable mixture of the diastereo-
mers.2,3 This often becomes a disadvantage of the above
type of reduction in terms of the stereoselective synthesis
of â-hydroxysulfoxides. Highly stereocontrolled synthesis
of R-substituted â-hydroxysulfoxides has been partly
achieved: Ogura4 and Guanti5 with their co-workers have
independently reported that reduction of R-(alkylthio)-
â-ketosulfoxides with NaBH4 or LiAlH4 in the presence
of tertiary amines such as triethylamine gives the
products with high stereoselectivity. They have assumed
that the highly diastereoselective outcome can be as-
cribed to the rapid equilibrium between the diastereo-
meric R-substituted â-ketosulfoxides through abstraction
and addition of an R-proton as well as to the reaction
* To whom correspondence should be addressed. Phone/Fax:
(+)81-52-735-5217.
(6) (a) Kusuda, S.; Ueno, Y.; Toru, T. Tetrahedron 1994, 50, 1045-
1062. (b) Toru, T.; Nakamura, S.; Takemoto, H.; Ueno, Y. Synlett 1997,
449-450. (c) Nakamura, S.; Watanabe, Y.; Toru, T. J . Chem. Soc.,
Perkin Trans. 1 1999, 3403-3404. (d) Ghorai, B. K.; Herndon, J . W.;
Lam, Y. Org. Lett. 2001, 3, 3535-3538. (e) Nakamura, S.; Uchiyama,
Y.; Ishikawa, S.; Fukinbara, R.; Watanabe, Y.; Toru, T. Tetrahedron
Lett. 2002, 43, 2381-2383. (f) Chambert, S.; De´sire´, L.; De´cout, J .-L.
Synthesis 2002, 2319-2334.
(7) (a) Nakamura, S.; Takemoto, H.; Ueno, Y.; Toru, T.; Kakumoto,
T.; Hagiwara, T. J . Org. Chem. 2000, 65, 469-474. (b) Nakamura, S.;
Watanabe, Y.; Toru, T. J . Org. Chem. 2000, 65, 1758-1766. (c)
Nakamura, S.;. Toru, T. J . Synth. Org. Chem., J pn. 2002, 60, 115-
124.
(1) (a) Solladie´, G.; Demailly, G.; Greck, C. Tetrahedron Lett. 1985,
26, 435-438. (b) Kosugi, H.; Konta, H.; Uda, H. J . Chem. Soc., Chem.
Commun. 1985, 211-213. (c) Solladie´-Cavallo, A.; Suffert, J .; Adib.
A.; Solladie´, G. Tetrahedron Lett. 1990, 31, 6649-6652.
(2) (a) Carreno, M. C.; Ruano, J . L. G.; Martin, A. M.; Pedregal, C.;
Rodrigues, J . H.; Rubio, A.; Sanchez, J .; Solladie´, G. J . Org. Chem.
1990, 55, 2120-2128. (b) Bueno, A. B.; Carreno, M. C.; Ruano, J . L.
G.; Pena, B.; Rubio, A.; Hoyos, M. A. Tetrahedron 1994, 50, 9355-
9364. (c) Ruano, J . L. G.; Maestro, M. C.; Sanchez, F. Tetrahedron:
Asymmetry 1995, 6, 2299-2312. (d) Ruano, J . L. G.; Maestro, M. C.;
Barros, D.; Gonzalez, A. M. Tetrahedron: Asymmetry 1996, 7, 1819-
1828.
(8) Larger amount of LDA lowered the yield of 5a .
(3) Barros, D.; Carreno, M. C.; Ruano, J . L. G.; Maestro, M. C.
Tetrahedron Lett. 1992, 33, 2733-2736.
(9) To confirm the product distribution, four diastereomeric isomers
5a A-D were separately prepared by the reaction of the R-carbanion
derived from the corresponding â-hydroxysulfoxide with (iodomethyl)-
trimethylsilane.
(4) Ogura, K.; Fujita, M.; Inaba, T.; Takahashi, K.; Iida, H.
Tetrahedron Lett. 1983, 24, 503-506.
(5) Guanti, G.; Narisano, E.; Pero, F.; Banfi, L.; Scolastico, C. J .
Chem. Soc., Perkin Trans. 1 1984, 189-193.
(10) Absolute configuration of 5c was determined by comparison of
the 1H NMR spectral data with the reported data; see ref 3.
10.1021/jo034285k CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/07/2003
5766
J . Org. Chem. 2003, 68, 5766-5768