Enantioselective reduction of α-substituted ketones mediated by the boronate ester TarB-NO2

A facile and mild reduction procedure is reported for the preparation of chiral secondary alcohols prepared from alpha-substituted ketones using sodium borohydride and the chiral boronate ester (L)-TarB-NO2. Direct reduction of substituted ketones bearing Lewis basic heteroatoms generally provided secondary alcohols of only modest enantiomeric excess likely due to either competition between the target carbonyl and the functionalized sidechains at the Lewis acidic boron atom in TarB-NO2 or the added steric bulk of the alpha-sidechain. As an alternative method, these substrates were synthesized using TarB-NO2 via a two-step procedure involving the reduction of an alpha-halo ketone to a chiral terminal epoxide, followed by regioselective/regiospecific epoxide opening by various nucleophiles. This procedure provides access to a variety of functionalized secondary alcohols including beta-hydroxy ethers, thioethers, nitriles, and amines with enantiomeric excesses of 94% and yields up to 98%. (C) 2010 Elsevier Ltd. All rights reserved.