TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 45–48
Enantioselective borane reduction of aromatic ketones catalyzed
by chiral aluminum alkoxides
I-Pin Fu and Biing-Jiun Uang*
Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 300, Republic of China
Received 6 December 2000; accepted 30 December 2000
Abstract—The asymmetric borane reduction of prochiral ketones with an alkoxide catalyst prepared in situ from aluminum
tri-iso-propoxide and (R)-binaphthol was examined. Using these conditions, alcohols were obtained in high yield and e.e.’s of up
to 83%. © 2001 Published by Elsevier Science Ltd. All rights reserved.
The synthesis of enantiomerically enriched alcohols is
an interesting challenge since they are often valuable
intermediates for the synthesis of natural products.
Among the variety of asymmetric reactions that may
lead to optically active alcohols, the enantioselective
reduction of prochiral ketones with borane and a chiral
ligand, following the pioneering works of Itsuno1 and
Corey,2 has received considerable attention.3 In a recent
study, organo-aluminum compounds have been
reported to accelerate the catalytic asymmetric borane
reduction of ketones.4 On the other hand, so far as we
know, there are no reports of using aluminum based
catalysts reported herein, which are easily obtainable
and inexpensive. Thus, we tried the asymmetric borane
reductions of acetophenone 2 using the complex A
readily generated in situ from aluminum iso-propoxide
and (R)-binaphthol 1 as catalyst (Scheme 1). A selec-
tion of results is presented in Table 1.
as in entry 9 gave only 50% yield with no enantioselec-
tivity after 24 hours (entry 10). This observation is in
agreement with those reported previously by Chan’s
group.5 It is also noteworthy that the presence of a
coordinative solvent appears to be deleterious to the
enantioselectivity of the reaction (entry 1). The selectiv-
ity was also found to be temperature dependent; when
the reaction was carried out at 0°C, phenylethanol was
obtained in only 50% yield with an e.e. of 39% after 48
hours (entry 13). Enantioselectivity also remained
unchanged when the ratio of aluminum tri-iso-propox-
ide and binaphthol was increased to 1:3 or 1:4, but
lower e.e. of 40% was obtained when the ratio was
decreased to 1:1.
To examine the efficacy of this catalytic process with
regards to substrate structure, a variety of aromatic
ketones were subject to the conditions optimized in the
case of acetophenone, and the results are summarized
in Table 2. When ketones 2–5 were subjected to reac-
tion (entries 1–4), the e.e. of the resulting alcohols
decreased as the size of the alkyl group increased,
except for propiophenone 3, which was reduced with
the highest enantioselectivity. A halogen substituent
Optimum results were obtained when the reaction was
carried out at 40°C in dichloromethane using the com-
plex prepared from 21 mol% of 1 and 10 mol% of
aluminum iso-propoxide (entry 9). Under these condi-
tions, the reaction was complete in 10 minutes and the
desired phenylethanol was isolated in 96% yield with an
e.e. of 74%. At the same time chiral ligand 1 was
recovered in 95% yield. It should be pointed out that
(R)-binaphthol alone is not a catalyst. In the absence of
aluminum iso-propoxide, the combination of (R)-
binaphthol and borane–dimethylsulfide complex for the
reduction of acetophenone under the same conditions
* Corresponding author. Tel.: 886-3-5721224; fax: 886-3-5711082;
e-mail: bjuang@mx.nthu.edu.tw
Scheme 1. Synthesis of complex A.
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