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 fluorinated beta-keto carboxylic esters and benzylamine. This transformation involves two sequential base-catalyzed [1,3]-proton transfers giving rise to corresponding N-benzylidene derivatives as the products of final thermodynamic equilibration, directed by the electron-withdrawing character of fluoroalkyl groups. Opportunity for catalytic enantiocontrolled synthesis of targeted beta-amino acids with application of monochiral base, as a catalyst for these isomerizations, is demonstrated. Copyright (C) 1996 Elsevier Science Ltd