BIOMIMETIC BASE-CATALYZED [1,3]-PROTON SHIFT REACTION - A PRACTICAL SYNTHESIS OF BETA-FLUOROALKYL-BETA-AMINO ACIDS

An efficient approach to practical synthesis of beta-fluoroalkyl-beta- amino acids is described. The method consists in the reducing reagent- free base-catalyzed biomimetic transamination reaction between fluorin ated beta-keto carboxylic esters and benzylamine. This transformation involves two sequential base-catalyzed [1,3]-proton transfers giving r ise to corresponding N-benzylidene derivatives as the products of fina l thermodynamic equilibration, directed by the electron-withdrawing ch aracter of fluoroalkyl groups. Opportunity for catalytic enantiocontro lled synthesis of targeted beta-amino acids with application of monoch iral base, as a catalyst for these isomerizations, is demonstrated. Co pyright (C) 1996 Elsevier Science Ltd