Title:Preparation of Optically Active Biphenyl Compounds via an Albumin-
Mediated Asymmetric Nitroaldol Reaction
Volume: 19
Issue: 2
Author(s): Kazutsugu Matsumoto*, Ryota Kitabayashi, Naoki Fukuchi and Noriyuki Suka
Affiliation:
- Department of Chemistry and Life Science, Meisei University, 2-1-1 Hodokubo, Hino, Tokyo 191-8506, Japan
Keywords:
Asymmetric nitroaldol reaction, biocatalysis, human serum albumin, 2-nitro alcohols, optically active biaryl compounds, reaction in water.
Abstract: Human serum albumin (HSA) was found to catalyze the asymmetric nitroaldol reaction
of biphenyl aldehydes with nitromethane to afford the corresponding optically active 2-nitro alcohols.
Careful optimization of the conditions for the reaction of 4-phenylbenzaldehyde with nitromethane
in water at a neutral pH improved both the reactivity and the enantioselectivity. Finally,
the reaction of 4-phenylbenzaldehyde (56 mg, 0.30 mmol) in nitromethane (2.8 mL) and water (1.1
mL) using HSA (68 mg) at 5 °C for 240 h gave (R)-1-([1,1'-biphenyl]-4-yl)-2-nitroethanol in 71%
yield (52 mg), with an ee up to 85% ee. Subsequent recrystallization improved the ee up to 95%.
The reaction was useful in a preparative-scale operation, and the biocatalyst could be reused several
times. The procedure was also applicable to other substrates with different substitution patterns.
Although the nitroaldol reaction of 2-phenylbenzaldehyde with nitromethane proceeded with low
enantioselectivity to afford the corresponding (R)-2-nitroalcohols (35% ee), the reactions of the
substrates bearing Br, Me, OMe, or CN group at the 4'-position of the benzene ring gave the corresponding
optically active compounds with high enantioselectivities (80-88% ee).
