Baker's yeast-mediated preparation of optically active aryl alcohols and diols for the synthesis of chiral hydroxy acids

Abstract

Baker's yeast reduction of 1-(4-methoxyphenyl)propan-2-one, 4-phenylbutan-2-one, and 2-hydroxy-1-(4-methoxyphenyl)ethanone (p-methoxyphenacyl alcohol), afforded in good yield and high optical purity the corresponding (S)-alcohols and the (R)-diol, but only after careful investigation of incubation conditions. Protection of the above hydroxy compounds, and ruthenium tetraoxide oxidation of their acetates, afforded the corresponding acetoxy acids in good yield and high optical purity. (S)-1-(p-Methoxyphenyl)ethane-1,2-diol could be prepared either by baker's yeast incubation of the acetate of p-methoxyphenacyl alcohol or 2-acetoxy-1-(4-methoxyphenyl)ethanone (24% yield, 82% ee) or from its (R)-enantiomer via a Mitsonobu reaction on its mono t-butyldimethylsilyl ether.