DEDICATED TO PROFESSOR HC BROWN ON HIS ... - Sigma-Aldrich

orane reductions 29,30 of 1,4-diphenyl-1,4butanedione
and its reduction with 4 31
produced the corresponding 1,4-diol with
high ee’s and de’s (eq 4).
3.2. α-Halo and α-Sulfonyloxy
Ketones
The asymmetric reductions of α-bromoand
α-chloroacetophenone, among the
α-halo ketones, have been the most studied
(eq 5). Reductions with 4, 9 5, 32 and most of
the oxazaborolidine- and other-ligandcatalyzed
reductions19,22,23,25b,33,34 provided 2halo-1-phenylethanols
with high ee’s. The
chiral borohydrides 1 and 2 afforded 77%
and 92% ee’s, respectively. 6,7 Reductions of
trihalomethyl ketones with 11c/CB or with 4
afforded the corresponding trihalomethyl
Styrene Oxide
Reduction Conditions Yield (%) % ee
1 (1.1 equiv), -78 °C 82 77, S
2 (1.1 equiv), -78 °C 99 92, S
4 (1.2 equiv), -25 °C 90 96, R
5 (neat), rt 91 96, R
11a (0.02 equiv), BH3:THF (0.5 equiv), rt 97 96, S
13a (0.1 equiv), BMS (0.5 equiv), -20 °C >90 92, S
15b (0.1 equiv), BH3:THF (0.8 equiv), -20 °C >90 96, S
16 (0.1 equiv), BMS (1.2 equiv), rt 84 84, S
17 (0.1 equiv), BMS (1.0 equiv), 110 °C 91 94, S
19a (0.15 equiv), NaBH4–TMSCl, 65 °C 98 96, S
Trihalomethyl Carbinols
X R Reduction Conditions Yield (%) % ee
F aryl 11c (0.1 equiv), CB (1.5 equiv),
PhMe, -78 °C or -20 °C >90 94-100, R
F aryl 4 (neat, 1.1 equiv), 25 °C 48-93 78-90, S
F alkyl 4 (neat, 1.1 equiv), 25 °C 70-87 87-96, S
Cl aryl 11c (0.1 equiv), CB (2.0 equiv),
PhMe–THF, -70 °C 64-74 >98, R
Cl alkyl 11c (0.1 equiv), CB (1.5 equiv),
PhMe, -78 °C to 23 °C 94-97 92-98, R
CB = catecholborane
carbinols in 78–100% ee’s (eq 6). 35,36a 4 was
also effectively employed for preparing
1,1,1-trifluorooxirane in high ee by reduction
of 1-bromo-3,3,3-trifluoropropanone (eq 7). 36b
Optically active halohydrins or styrene
oxide derivatives, obtained by reduction of
α-halo ketones, have been widely used as
key intermediates in the synthesis of many
chiral drugs containing the β-amino alcohol
moiety (Figure 5). Examples of such drugs
include: (R)-denopamine (21), 37 (R)-isoproterenol
(22), 38 (R)-salmeterol (23), 39 and
(R,R)-formoterol (24). 40 However, the use
of α-halo ketones as starting materials
in commercial applications has severe
drawbacks: α-halo ketones cause skin and
eye irritation and are unstable to light. These
disadvantages were successfully overcome
by using the more stable and nonirritating
α-sulfonyloxy ketones. The CBS oxazaborolidine-catalyzed
reduction of α-sulfonyloxy
ketones using BACH-EI TM as the
hydride source provided the corresponding
1,2-diol monosulfonates and terminal
epoxides in very high ee’s (eq 8). 20e The
reduction with 4 also afforded high
enantioselectivities. 41 Using this methodology,
chiral drugs such as (R)-21, (R)-nifenalol
(25), and (R)-pronethalol (26) were prepared
highly enantioselectively by direct amination
of the corresponding optically active 1,2-diol
monosulfonates. 42 Moreover, enantiopure
(1S,2R)-indene oxide (27)—which is a key
starting material for the synthesis of
indinavir (28), a highly effective HIV
protease inhibitor—has been efficiently
prepared by the same reduction from
2-(p-toluenesulfonyloxy)-1-indanone (eq 9). 20f
VOL. 35, NO. 1 • 2002
eq 5
eq 6
eq 7
7