Rhodium-catalyzed asymmetric hydrogenation of beta-cyanocinnamic esters with the assistance of a single hydrogen bond in a precise position

With the assistance of hydrogen bonds, the first asymmetric hydrogenation of beta-yanocinnamic esters is developed, affording chiral beta-cyano esters with excellent enantioselectivities (up to 99% ee). This novel methodology provides an efficient and concise synthetic route to chiral GABA-derivatives such as (S)-Pregabalin, (R)-Phenibut, (R)-Baclofen. Interestingly, in this system, the catalyst with a single H-bond donor performs better than that with double H-bond donors, which is a novel discovery in the metalorganocatalysis area.