Practical, Catalytic Enantioselective Hydrogenation to Synthesize N-Unprotected β-Amino Esters

Practical and simple catalytic enantioselective hydrogenation reactions to synthesize N-unprotected beta-amino esters have been developed: (1) asymmetric hydrogenation of N-unprotected beta-enamine ester and (2) asymmetric direct reductive amination of beta-keto esters using ammonium salts. A Ru-DM-SEGPHOS complex was used as the catalyst in both cases and gave high enantioselectivity, high reactivity, and wide substrate applicability. These protocols greatly reduced reaction time and waste compared to conventional synthetic routes. The direct reductive amination route was demonstrated on a > 100 kg scale.