Direct Catalytic Asymmetric Aldol Reactions of Thioamides: Toward a Stereocontrolled Synthesis of 1,3-Polyols

A direct catalytic asymmetric aldol reaction of thioamides with a soft Lewis acid/hard Bronsted base cooperative catalytic system comprising (R,R)-Ph-BPE/[Cu(CH3CN)(4)]PF6/LiOAr is described. Highly chemoselective deprotonative activation of thioamides allows for a direct aldol. reaction of alpha-nonbranched aliphatic aldehydes, which are susceptible to self-condensation. Facile reduction of the thioamide functionality and a catalyst-controlled second aldol reaction provides 1,3-diols in a highly stereoselective manner.