Highly enantioselective synthesis of alpha,beta-diaminopropanoic acid derivatives using a catalytic asymmetric hydrogenation approach

Rh-DuPhos-catalyzed asymmetric hydrogenation of alpha,beta -diamidoacrylate s provides a highly efficient and enantioselective route to chiral alpha,be ta -diaminopropanoic acid derivatives. The mechanistic course of the hydrog enation was studied using isotopically enriched enamide complexes and phosp horus and carbon NMR. Addition of methyl alpha -N-benzoyl-beta -N-acetyl-di aminopropenoate to the solvated catalyst gave a single 1:1 enamide complex and demonstrated the binding of the olefin and alpha -amide carbonyl group; the carboxylate and beta -N-acyl groups did not bind to the metal. Changes to the electronic and steric properties of the beta -N-acyl group were wel l tolerated; however, small changes to the binding alpha -N-acyl group were found to significantly affect hydrogenation yields.