A convenient asymmetric synthesis of alpha-1-arylalkylamines through the enantioselective hydrogenation of enamides

We have found that cationic Rh catalysts based on our 1,2-bis(trans-2,5 dimethylphospholano)benzene (Me-DuPHOS) and 1,2-bis(trans-2,5-dimethylphospholano)ethane (Me-BPE) ligands effect the hydrogenation of N-acetyl α-arylenamides (1, R = H) to yield a wide variety of valuable α-1-arylethylamine derivatives with high enantioselectivites (≥ 90% ee). Moreover, an important and unique feature of our catalysts is the ability to tolerate β-substitutents in both (E)- and (Z)-positions of enamides 1, thus allowing the production of a diverse array of α-1-arylalkyamines 2 through hydrogenation of isomeric mixtures of enamide substrates. Our Me-DuPHOS-Rh and Me-BPE-Rh catalysts have been found to allow efficient hydrogenation of α-arylenamides 1, thus providing practical access to a broad range of valuable α--1-arylalkylamine derivatives in highly enantiomerically enriched form. A unique feature of this system is the ability of our catalysts to hydrogenate mixtures of (E)- and (Z)-enamides with high enantioselectivities, hence obviating the need to prepare isomerically pure substrates. The present study further demonstrates the versatility and utility of our DuPHOS-Rh and BPE-Rh hydrogenation catalysts for the production of chiral building blocks of medicinal and biological interest.