Highly efficient synthesis of β-amino acid derivatives via asymmetric hydrogenation of unprotected enamines: Scope and mechanistic studies

ORGN 16

Thorsten Rosner, Yi Hsiao, Nelo R. Rivera, Shane W. Krska, Eugenia Njolito, Fang Wang, Yongkui Sun, Joseph D. Armstrong III, Edward J. J. Grabowski, and Rich D. Tillyer. Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065
A novel hydrogenation reaction for the highly enantioselective formation of β-amino acid derivatives is described. This procedure involves rhodium catalyzed hydrogenation of unprotected β-enamine esters and amides, obviating the need for protecting group chemistry. The mechanism of this unprecedented transformation has been probed by a combination of kinetics, deuterium labeling studies and reactions of model compounds. Results suggest the intriguing possibility that the reaction proceeds through the β-imino ester (amide) tautomer. These results will be discussed in terms of their synthetic implications.

 

Asymmetric Reactions and Syntheses
8:00 AM-12:00 PM, Sunday, August 22, 2004 Pennsylvania Convention Center -- 201A, Oral

Division of Organic Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004