Asymmetric hydrogenation: A new method for the synthesis of β-amino acid derivatives

ORGN 525

Yi Hsiao, Nelo R. Rivera, Thorsten Rosner, Shane W. Krska, Eugenia Njolito, Karl Hansen, Fang Wang, Yongkui Sun, Joseph D. Armstrong III, Edward J. J. Grabowski, and Rich D. Tillyer. Department of Process Research, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, NJ 07065
During the course of development of synthetic routes to a β-amino acid investigational drug candidate, we have discovered an unprecedented enantioselective reduction of unprotected enamino esters and amides using commercially available ligands under mild hydrogenation conditions. This method gives high enantioselectivity, high reactivity, and wide applicability, and requires no protecting groups. Contrary to accepted thinking, our results clearly show that the N-acyl group is not a prerequisite for such transformations to be effective.