Regioselective synthesis of fluoroaldols. Studies toward fluoroepothilones syntheses via antibody catalysis

A general method for the synthesis of fluoromethyl aldols has been developed. Tributylboron enolates of fluoroacetone react with thiazole aldehydes (6) to provide fluoromethylaldols (4) regioselectively in high yields. Regioisomeric fluoroaldols (5) are produced as a 1:1 isomeric mixture of the erythro and threo products via a two-step procedure: first, aldol reaction with Weinreb amide and then Grignard reaction.