Enantioselective Synthesis of beta-Arylamines via Chiral Phosphoric Acid-Catalyzed Asymmetric Reductive Amination

Abstract

A new method for the synthesis of chiral beta-aryl amines via chiral phosphoric acid-catalyzed enantioselective reductive amination of benzyl methyl ketone derivatives with Hantzsch ester was developed. Various chiral beta-aryl amines were obtained in high yields and with good to high enantioselectivities. This transformation is applicable to gram-scale reactions, and the catalyst loading can be reduced to 1 mol % without sacrificing any catalytic efficacy. Furthermore, the resulting beta-aryl amine was successfully converted into a tetrahydroisoquinoline compound without any loss of enantioselectivity.