Enantioselective Synthesis of α-Hydroxy Amides and β-Amino Alcohols from α-Keto Amides

Abstract

Synthesis of enantiomerically enriched α-hydroxy amides and β-amino alcohols has been accomplished by enantioselective reduction of α-keto amides with hydrosilanes. A series of α-keto amides were reduced in the presence of chiral Cu(II)/(S)-DTBM-SEGPHOS catalyst to give the corresponding optically active α-hydroxy amides with excellent enantioselectivities by using (EtO)3SiH as a reducing agent. Furthermore, a one-pot complete reduction of both ketone and amide groups of α-keto amides has been achieved using the same chiral copper catalyst followed by tetra-n-butylammonium fluoride (TBAF) catalyst in presence of (EtO)3SiH to afford the corresponding chiral β-amino alcohol derivatives.

Keywords: amides; amino alcohols; enantioselectivity; reduction; silanes.