Enantioselective Synthesis of α,α-Difluoro-β-amino Acid and 3,3-Difluoroazetidin-2-one via the Reformatsky-Type Reaction of Ethyl Bromodifluoroacetate with Chiral 1,3-Oxazolidines

Abstract

Chiral oxazolidines 2a − e can be diastereoselectively alkylated with BrCF 2 CO 2 Et to furnish 3,3-difluoroazetidin-2-ones 3a − e with up to 99% de. Selective cleavage of the chiral appendage provided the corresponding unsubstituted azetidinones. Formation of optically pure α,α-difluoro-β-amino acids 5a − c can be achieved by acidic hydrolysis of N -vinyl-azetidin-2-ones.