Catalytic asymmetric borane reduction of prochiral ketones by the use of chiral β-diamines

Article abstract of DOI:10.1246/cl.2000.990

The catalytic asymmetric borane reduction of prochiral ketones was examined in the presence of chiral β-diamines. Chiral secondary alcohols were obtained with modest to high enantiomeric excesses (up to 92% ee) using (S)-2-[(p-trifluoromethyl)anilinomethyl]indoline.

Full text of DOI:10.1246/cl.2000.990

990
Chemistry Letters 2000
Catalytic Asymmetric Borane Reduction of Prochiral Ketones by the Use of
Chiral β-Diamines
Masatoshi Asami,* Shinsuke Sato, and Hiroyasu Watanabe
Department of Chemistry and Biotechnology, Faculty of Engineering, Yokohama National University,
Tokiwadai, Hodogaya-ku, Yokohama 240-8501
(Received June 7, 2000; CL-000552)
The catalytic asymmetric borane reduction of prochiral
equiv of 1 and 0.60 equiv of borane–THF complex. (R)-1-
ketones was examined in the presence of chiral β-diamines.
Chiral secondary alcohols were obtained with modest to high
enantiomeric excesses (up to 92% ee) using (S)-2-[(p-trifluoro-
methyl)anilinomethyl]indoline.
Phenylethanol was obtained after stirring for 16 h at room tem-
perature in good yield (93%) with low ee (14% ee). When (S)-2-
(anilinomethyl)indoline (2a)9 was used instead of 1, the reaction
proceeded rapidly and the enantioselectivity was dramatically
increased to 83% (R). However (S)-2-(cyclohexylamino-
methyl)indoline (3)9 required long reaction time and showed low
selectivity (9% ee). Thus it is noteworthy that the aromatic rings
on both nitrogen atoms of diamine are necessary to achieve both
high catalytic activity and high selectivity (Table 1).
Next, the substituent effect of the aromatic ring of the side
chain of diamine 29 was examined. The results are summarized
in Table 2. The selectivity was decreased when sterically hin-
dered diamine 2b or 2c was used (Entries 2,3). Diamine 2d or
2e having trifluoromethyl group(s) gave improved selectivity
(Entries 4,5). The best result (88%, 92% ee) was obtained
when the reaction was carried out at lower temperature (–15
°C) for 2 h using 0.15 equiv of 2d and 1.0 equiv of
borane–THF complex (Entry 6).
The preparation of enantiomerically enriched secondary
alcohols by catalytic enantioselective borane reduction of
prochiral ketones has been studied extensively after the original
studies of Itsuno et al.1 and Corey et al..2 Usually the reaction
is promoted effectively by the chiral catalyst generated by the
reaction of borane and chiral amino alcohols,3 sulfoximines,4
phosphinamides,5 or a mercapto alcohol.6 There have been no
reports using chiral β-diamines for the modification of borane
to the best of our knowledge. Thus we examined the effective-
ness of chiral β-diamines in the reaction as we have been study-
ing asymmetric reactions by the use of chiral β-diamines
derived from (S)-proline7 or (S)-2-indolinecarboxylic acid.8
Here we wish to report that the selectivity of the reaction large-
ly depends on the structure of the diamine and high selectivity
(up to 92% ee) was achieved in the case of aromatic ketones
using (S)-2-[(p-trifluoromethyl)anilinomethyl]indoline.
In the first place, an enantioselective reduction of acetophe-
none was examined in the presence of a catalytic amount of (S)-2-
(anilinomethyl)pyrrolidine (1), which was effective for the modi-
fication of lithium aluminum hydride in our previous work.7a The
reaction was carried out in THF at room temperature using 0.10
Then asymmetric reduction of other prochiral ketones was
carried out under the optimized reaction conditions. As shown
in Table 3, relatively high enantioselectivities were achieved for
aromatic ketones.
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
991
References and Notes
1
2
3
S. Itsuno, K. Ito, A. Hirao, and S. Nakahama, J. Chem.
Soc., Chem. Commun., 1983, 469.
E. J. Corey, R. K. Bakshi, and S. Shibata, J. Am. Chem.
Soc., 109, 5551 (1987).
For reviews: L. Deloux and M. Srebnik, Chem. Rev., 93,
763 (1993); E. J. Corey and C. J. Helal, Angew. Chem., Int.
Ed. Engl., 37, 1986 (1998); For recent examples: P. Pinho,
D. Guijarro, and P. G. Andersson, Tetrahedron, 54, 7897
(1998); M. Shimizu, K. Tsukamoto, T. Matsutani, and T.
Fujisawa, Tetrahedron, 54, 10265 (1998); T. Yanagi, K.
Kikuchi, H. Takeuchi, T. Ishikawa, T. Nishimura, and T.
Kamijo, Chem. Lett., 1999, 1203; C. Puigjaner, A. V.
Ferran, A. Moyano, M. A. Pericàs, and A. Riera, J. Org.
Chem., 64, 7902 (1999).
4
5
6
7
C. Bolm and M. Felder, Tetrahedron Lett., 34, 6041
(1993).
M. P. Gamble, A. R. C. Smith, and M. Wills, J. Org.
Chem., 63, 6068 (1998).
T. K. Yang and D. S. Lee, Tetrahedron: Asymmetry, 10,
405 (1999).
a) M. Asami, H. Ohno, S. Kobayashi, and T. Mukaiyama,
Bull. Chem. Soc. Jpn., 51, 1869 (1978). b) M. Asami, Bull.
Chem. Soc. Jpn., 63, 721 (1990). c) M. Asami, K. Usui, S.
Higuchi, and S. Inoue, Chem. Lett., 1994, 297. d) M.
Asami, T. Ishizaki, and S. Inoue, Tetrahedron:
Asymmetry, 5, 793 (1994). e) M. Asami and S. Inoue, Bull.
Chem. Soc. Jpn., 70, 1687 (1997). f) M. Asami, S. Sato, K.
Honda, and S. Inoue, Heterocycles, 52, 1029 (2000).
M. Asami, H. Watanabe, K. Honda, and S. Inoue,
Tetrahedron: Asymmetry, 9, 4165 (1998).
At present, we assume that diazaborolidine 4 generated by
the reaction of diamine 2 and borane would be an actual cata-
lyst of the reaction. After the coordination of BH3 to the nitro-
gen atom of indoline ring of catalyst 4, ketone approaches in a
manner as shown in Scheme 1. Thus the alcohol having the
configuration shown in Table 3 was obtained preferentially.
8
9
All new compounds are fully characterized by IR, 270
MHz 1H-NMR, mass spectra and/or elemental analysis.
10 W. S. Huang, Q. S. Hu, and L. Pu, J. Org. Chem., 64, 7940
(1999).
11 Typical experimental procedure (Table 2, Entry 6) is as
follows; Under an argon atmosphere borane–THF complex
(1.0 M THF solution, 1.0 mL, 1.0 mmol) was added to a
THF (0.5 mL) solution of 2d (44 mg, 0.15 mmol) at 0 °C
and stirring was continued for 0.5 h at the temperature.
Then the reaction mixture was cooled to –15 °C and a THF
(1.5 mL) solution of acetophenone (120 mg, 1.0 mmol)
was added dropwise via syringe over two hours. The reac-
tion mixture was stirred at the temperature for further two
hours. After an addition of 1 M HCl at the temperature,
the reaction mixture was stirred at room temperature for 10
min. The reaction mixture was extracted twice with ether,
and the combined organic layers were washed with 1 M
HCl, water, and brine, successively. The organic layer was
dried over anhyd MgSO4 and the solvent was removed in
vacuo. The resulting crude product was purified by silica-
gel column chromatography (hexane:ether = 3:1), followed
by bulb-to-bulb distillation (170 °C/15 mmHg) to give (R)-
The catalytic activity of diamine 2 was increased and non-
catalytic reaction was diminished, because Lewis aciditiy of
boron atom in 4 was intensified by two aromatic rings on nitro-
gens. This effect was amplified by introducing trifluoromethyl
group on the aromatic ring.
In summary, this study revealed that a novel chiral β-
diamine derived from (S)-2-indolinecarboxylic acid, catalyzed
asymmetric borane reduction of prochiral ketones effectively,
and chiral secondary alcohols were obtained with high ee by the
reduction of aromatic ketones.
20
1-phenylethanol (108 mg, 88%, [α]D +52.5 (c 1.00,
CHCl3)). The ee was determined by HPLC analysis using
a Daicel Chiralcel OD-H column to be 92% ee.