Robinson A J, Lim C Y, He L, Ma P, Li H Y
DuPont Pharmaceuticals Company, Chemical Process R&D, Experimental Station, Wilmington, Delaware 19880-0336, USA.
J Org Chem. 2001 Jun 15;66(12):4141-7. doi: 10.1021/jo001151n.
Rh-DuPhos-catalyzed asymmetric hydrogenation of alpha,beta-diamidoacrylates provides a highly efficient and enantioselective route to chiral alpha,beta-diaminopropanoic acid derivatives. The mechanistic course of the hydrogenation was studied using isotopically enriched enamide complexes and phosphorus and carbon NMR. Addition of methyl alpha-N-benzoyl-beta-N-acetyl-diaminopropenoate 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 well tolerated; however, small changes to the binding alpha-N-acyl group were found to significantly affect hydrogenation yields.
