Efficient synthesis of an optically pure β-bromo-β,β-difluoroalanine derivative, a general precursor for β,β-difluoroamino acids

A highly efficient enantioselective preparation of a beta -bromo-beta,beta -difluoroalanine derivative, a promising general precursor for optically active beta,beta -difluoroamino acids, is described. Alkylation of the hydroxypinanone glycinate Schiff base 2a with CF2Br2 resulted in the production of undesired dehydrobrominated product 4a promoted by the lithium alkoxide moiety on the hydroxypinanone chiral auxiliary. Dehydrobromination was prevented by protection of the hydroxyl group on the chiral auxiliary. Utilization of TMSOTf resulted in production of (S,S,S,S)-3b as the sole diastereomer without dehydrobromination. Further transformations of (S,S,S,S)-3b to other optically active beta,beta -difluoroamino acids were demonstrated. (C) 2001 Elsevier Science Ltd. All rights reserved.