Diastereoselective reduction of chiral α-ketoamides derived from (S)-proline esters with sodium borohydride. Preparation of optically active α-hydroxy acids

Abstract

Diastereoselective reductions of chiral α-ketoamides (3) derived from (S)-proline esters (2) with sodium borohydride were examined. Hydrolysis of the reduction products afforded optically active α-hydroxy acids (5) in good enantiomeric excesses (e.e.). The most influential factor of the asymmetric induction was the effect of using a mixed hydroxylic and non-hydroxylic solvent. The degree of asymmetric induction varied considerably with the ratio of alcohol and tetrahydrofuran (THF) in the mixed solvent. With aromatic ketoamides (3), higher asymmetric induction occurred in a mixed alcohol–THF solvent than in the corresponding individual solvents.