A New Strategy for the Synthesis of α-Difluoromethyl-Substituted α-Hydroxy and α-Amino Acids

A new method for the preparation of α-chlorodifluoromethyl-, α-bromodifluoromethyl-, and α-difluoromethyl-substituted α-hydroxy and α-amino acid esters 11, 19−21 is described. The key step of the synthesis is the regioselective alkylation of ketones 5, 7−9 and imines 16−18 with C-nucleophiles. The ketones 7−9 are readily available from 3,3,3-trifluorolactate 1 by a five-step procedure. Subsequent removal of the protecting groups from 19−21 provides the corresponding free amino acids 25, 26, 28.