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

A highly efficient enantioselective preparation of a beta -bromo-beta,beta -difluoroalanine derivative, a promising general precursor for optically ac tive beta,beta -difluoroamino acids, is described. Alkylation of the hydrox ypinanone glycinate Schiff base 2a with CF2Br2 resulted in the production o f undesired dehydrobrominated product 4a promoted by the lithium alkoxide m oiety on the hydroxypinanone chiral auxiliary. Dehydrobromination was preve nted by protection of the hydroxyl group on the chiral auxiliary. Utilizati on of TMSOTf resulted in production of (S,S,S,S)-3b as the sole diastereome r without dehydrobromination. Further transformations of (S,S,S,S)-3b to ot her optically active beta,beta -difluoroamino acids were demonstrated. (C) 2001 Elsevier Science Ltd. All rights reserved.