Practical and efficient procedure for the in situ preparation of B-alkoxyoxazaborolidines. Enantioselective reduction of prochiral ketones

Article abstract of DOI:10.3390/50300495

A new method for the in situ elaboration of B-alkoxyoxazaborolidines is presented. Their use in the enantioselective reduction of prochiral aromatic ketones provides excellent chemical and optical yields of chiral alcohols.

Full text of DOI:10.3390/50300495

495
Molecules 2000, 5
Practical and Efficient Procedure for the In Situ Preparation of
B-Alkoxyoxazaborolidines. Enantioselective Reduction of
Prochiral Ketones
Viviana L. Ponzo and Teodoro S. Kaufman
Instituto de Química Orgánica de Síntesis -IQUIOS-(CONICET-UNR) and Facultad de Ciencias Bio-
químicas y Farmacéuticas, Universidad Nacional de Rosario, P.O.B. 991, 2000 Rosario, Argentina
E-mail: tkaufman@agatha.unr.edu.ar
Abstract: A new method for the in situ elaboration of B-alkoxyoxazaborolidines is pre-
sented. Their use in the enantioselective reduction of prochiral aromatic ketones provides
excellent chemical and optical yields of chiral alcohols.
Since the development of Corey [1], the B-alkyloxazaborolidines (OAB) have gained reputation as
efficient catalysts in the enantioselective reduction of prochiral ketones. In addition to provide alcohols
in high optical purity [2], they can be employed in small quantities and their reaction mechanism al-
lows the prediction of the stereochemistry of the newly generated chiral center.
Numerous OAB synthesized from different aminoalcohols have been reported [3], however the
most used OAB is that derived from α,α-diphenylpyrrolidinemethanol (8) developed by Corey.
In spite of the advantages of this new type of catalysts, the various methods described for their ob-
tention, many times discourage their use, being time consuming [4] or requiring extensive separation
steps prior to their use [5].
In order to avoid these inconvenients, we decided to study the synthesis of B-
alkoxyoxazaborolidines, reacting alkyl borates with 8 by analogy with the strategies reported for the
elaboration of alkyl-OAB, and then to evaluate the ability of the product to enantioselectively reduce
prochiral aromatic ketones.
In this communication we introduce a new, practical and efficient method for the in situ elaboration
of B-alkoxyoxazaborolidines employing inexpensive reagents and avoiding separation steps which
could alter the optical quality of the reduction.
We also demonstrate the efficiency and capability of the B-alkoxyoxazaborolidines as catalysts
through the reduction of several substituted acetophenones. The enantioselectivity obtained is gener-
ally comparable to that observed with the B-methyloxazaborolidine developed by Corey.

496
Molecules 2000, 5
Ph
Ph
N
H
Ph
H
N
Ph
BH3.SMe2
OH
8
[(RO)3B]
ROH
O
B
ArMe, 1h 34 C
OR
1 R= Me
2 R= Et
3 R= 1-Pr
4 R=2-Pr
5 R= 1-Bu
6 R= 1-Oct
7 R= c-Hex
1a-7a
B-alkoxyoxazaborolidines
Product
B-alkoxy-OAB
ee(%)
Yield (%)
R-1-(3,4-dimethoxyphenyl)ethanol
R-1-(4-acetoxy-3-methoxyphenyl)ethanol
R-1-(4-hydroxy-3-methoxyphenyl)ethanol
R-1-(2,4-dimethoxyphenyl)ethanol
R-1(4-nitrophenyl)ethanol
>95
97
>93
≈100
98
1a-7a
5a
>98
90
6a
6a
≈100
≈100
≈100
98
>95
95
6a
R-1(4-aminophenyl)ethanol
6a
R-1(4-bromophenyl)ethanol
97
6a
Acknowledgements: To Fundación Antorchas, CONICET, SECyT-UNR, AUGM and ANPCyT for
grants received. VLP thanks CONICET for a fellowship.
References and Notes
1. Corey, E. J.; Shibata, S.; Bakshi, R. J. Am. Chem. Soc. 1987, 109, 5551.
2. Corey, E. J.; Helal, C. Angew. Chem. Int. Ed. Eng. 1998, 37, 1986.
3. Wallbaum, S.; Martens, J. Tetrahedron: Asymmetry 1992, 3, 1475.
4. Corey, E. J.; Bakshi, R. Tetrahedron Lett. 1990, 31, 611.
5. Mathre, D.; Jones, T.; Xavier, L.; Blacklock, L. T.; Reamer, R.; Mohan, J.; Turner Jones, T.;
Hoogsteen, K.; Baum, M.; Grabowski, E. J. J. Org. Chem. 1991, 56, 751.
6. Masui, M.; Shiori, T. Synlett 1997, 273.