A new strategy for the synthesis of alpha-difluoromethyl-substituted alpha-hydroxy and alpha-amino acids

A new method for the preparation of alpha-chlorodifluoromethyl-, alpha-bromodifluoromethyl-, and alpha-difluoromethyl-substituted alpha-hydroxy and alpha-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 I by a five-step procedure. Subsequent removal of the protecting groups from 19-21 provides the corresponding : free amino acids 25, 26, 28.