J . Org. Chem. 2001, 66, 303-304
303
Sch em e 1. Asym m etr ic Red u ction of Keton es by
Asym m etr ic Bor a n e Red u ction of P r och ir a l
Keton es by P olym er -Su p p or ted Ch ir a l
Su lfon a m id es
Hom ogen ou s Ch ir a l Su lfon a m id e 2.
J ian-bing Hu, Gang Zhao,* Gao-sheng Yang, and
Zuo-ding Ding
Shanghai Institute of Organic Chemistry, Chinese Academy
of Science, 354 Fenglin Lu, Shanghai 200032, China
zhaog@pub.sioc.ac.cn
Received May 22, 2000
Polymer-supported (PS) sulfonamides have been pre-
pared by treating polymeric sulfonyl chlorides with (S)-
diphenylprolinol. The PS sulfonamides were investigated
as catalysts for the reduction of ketones by borane-
dimethyl sulfide complex. When the reductions were
conducted in refluxing THF with 15mol % 1f as catalyst,
excellent chemical yields and enantiomeric excess were
obtained. In addition to being recyclable, the catalyst
provided greater enantioselectivity than the homoge-
neous catalyst 2.
Sch em e 2 . P r ep a r a tion of P olym er -Su p p or ted
Ch ir a l Su lfon a m id es
The enantioselective reduction of prochiral ketones by
chiral catalysts and reagents has received intensive
interests in the past 20 years.1 A variety of homogeneous
chiral catalysts and reagents have been developed for the
reduction.2 However, the recovery and purification of
these catalysts and reagents are problematic. Immobili-
zation of chiral catalysts or reagents offers a solution to
the problem. The intrinsic advantages of polymer-sup-
ported catalysts are that they can be used in excess and
recovered by filtration at the end of reaction without loss
of activity.3 Several polymer-supported catalysts derived
from chiral amino alcohol have been developed for
reductions, but only few of them have displayed a high
enantioselectivity due to the polymer matrix restricting
the mobility of the catalytic site.4
Recently, we reported that the reduction of aromatic
ketones using a catalytic amount (10 mol %) of homoge-
neous chiral sulfonamides provided secondary alcohols
with 55-91% ee5 (Scheme 1). We demonstrated that
stereoselectivity is temperature dependent, with higher
reaction temperatures preferable (refluxing toluene).
Under the optimal reaction conditions, homogeneous
sulfonamide 2 was applied to the reductions of acetophe-
none and R-bromoacetophenone to give 55% ee and 85%
ee, respectively.
Resu lts a n d Discu ssion
Syn th esis of Ca ta lysts. The preparation of 1 is a two-
step sequence starting from styrene-divinylbenzene
cross-linked polymers (1% or 2% divinylbenzene) (Scheme
2). Initially, chlorosulfonylation of the polymer beads was
performed as described in the literature.6 We made an
effort to maximize the amount of loading sites in the
beads in order to increased the density of reactive sites,
but full chlorosulfonylation of 3 was not achieved. Ir-
respective of the cross-linking in the original resin (1 or
2%), the post-sulfonylated resin has 4.1-4.7 mmol/g of
available sulfonyl chloride. The second step, the synthesis
of the polymer-supported chiral sulfonamides was ac-
complished by treating 4 with an excess of (s)-diphenyl-
prolinol in the presence of Et3N in CH2Cl2.
In this paper, we report asymmetric reduction of
prochiral ketones in the presence of polymer-supported
chiral sulfonamides 1 as catalysts.
Exa m in a tion of Rea ction Con d ition s. It is well-
known that the stereoselectivity of reduction is effected
profoundly by solvent, temperature and the amount of
catalyst. To examine these effects, the reduction of
acetophenone was investigated at various reaction condi-
tions. Two solvents (THF and toluene) and a wide range
of 1% and 2% cross-linked polystyrene resins with
different degrees of functionalization were investigated.
Typical procedure for the reduction: BH3‚SMe2 (0.11
mmol) was added to a suspension of the catalyst in THF
(5 mL). The suspension was stirred and refluxed for 1h.
Then a THF (5 mL) solution of acetophenone (0.121 g,
0.1 mmol) was added slowly in 30 min. After the reaction
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A.; Owa, M.; Kanda, N.; Nakahama, S. Ibid 1985, 2615. (c) Itsuno, S.;
Sakuri, Y.; Shimizu, K.; Ito, K. Ibid 1990, 1859. (d) Caze, C.; EI Moualij,
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Asymmetry 1999, 10, 4307.
(6) Emerson, D. W.; Emerson, R. R.; J oshi, S. C.; Sorensen, E. M.;
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10.1021/jo000779v CCC: $20.00 © 2001 American Chemical Society
Published on Web 12/01/2000