Organic base-catalyzed stereodivergent synthesis of (R)- and (S)-3-amino-4,4,4-trifluorobutanoic acids

Abstract

Organic base-catalyzed reaction of (S)-N-tert-butanesulfinyl (3,3,3)-trifluoroacetaldimine with dialkyl malonates was found to be effective for synthesis of both (S,S_S) and (R,S_S) β-aminomalonates in high yield with good to excellent diastereoselectivity (76–98% de). The products of this Mannich reaction provide direct access to β-trifluoromethyl-β-alanine of either (R) or (S) absolute configuration.