Operationally convenient asymmetric synthesis of (S)- and (R)-3-amino-4,4,4-trifluorobutanoic acid: Part II. Enantioselective biomimetic transamination of 4,4,4-trifluoro-3-oxo-N-[(R)-1-phenylethyl]butanamide

An asymmetric synthesis of (S)- and (R)-3-amino-4,4,4-trifluorobutanoic acid via DBU-catalyzed asymmetric 1,3-proton shift transfer reaction of (Z)-3-[(R)-1-phenylethylamino]-4,4,4-trifluoro-N-[(R)-1-phenylethyl]but-2-enamide has been developed. The intermediate Schiff base (S,R′)-9 was found to be relatively configurationally stable under the highly basic reaction conditions allowing preparation of the target amino acid in high chemical yield and enantioselectivity. This method was demonstrated to be practical for large (>25 g) scale synthesis of the target β-amino acid.