Enantioselective reduction of ketones with NaBH 4/diglyme possibly catalysed by trialkyl borate: optically active sec-alcohols from prochiral ketones with catalytic (−)-menthol: autocatalysis option

Abstract

Ketones can be reduced with NaBH 4 in diglyme without an apparent proton source, but putatively catalysed by a trialkyl borate. This can be initially derived in situ from NaBH 4 and an alcohol, although the reaction becomes increasingly autocatalytic with time. With (−)-menthol as the initiating alcohol, the enantioselective reductions of a range of prochiral ketones in quantitative yields and moderate ees (generally 58–87%) were realised (the autocatalysis was demonstrated in two cases; catalysis by tris-(−)-menthyl borate was demonstrated in one case). The mechanism may involve either the activation of the substrate (electrophilically) or of the hydride reagent (nucleophilically). This method offers a relatively simple and inexpensive approach to a key transformation in asymmetric synthesis.