Operationally convenient asymmetric synthesis of (S)- and (R)-3-amino-4,4,4-trifluorobutanoic acid: Part I: Enantioselective biomimetic transamination of isopropyl 4,4,4-trifluoro-3-oxo-butanoate

DBU-catalyzed asymmetric synthesis of (S)- and (R)-3-amino-4,4,4-trifluorobutanoic acid via enantioselective biomimetic transamination of isopropyl 4,4,4-trifluoro-3-oxobutanoate with (R)- and (S)-phenylethylamine has been developed. The effect of the base concentration of the reaction rate and stereochemical outcome has been systematically studied. The key reaction step, DBU-catalyzed 1,3-proton shift transfer was found to be highly enantioselective (>95% ee). However, due to some racemization of the intermediate Schiff base under the highly basic reaction conditions leads to the final product of lower enantiomeric purity.