Highly Enantioselective Synthesis of α,β-Diaminopropanoic Acid Derivatives Using a Catalytic Asymmetric Hydrogenation Approach

Rh-DuPhos-catalyzed asymmetric hydrogenation of α,β-diamidoacrylates provides a highly efficient and enantioselective route to chiral α,β-diaminopropanoic acid derivatives. The mechanistic course of the hydrogenation was studied using isotopically enriched enamide complexes and phosphorus and carbon NMR. Addition of methyl α-N-benzoyl-β-N-acetyl-diaminopropenoate to the solvated catalyst gave a single 1:1 enamide complex and demonstrated the binding of the olefin and α-amide carbonyl group; the carboxylate and β-N-acyl groups did not bind to the metal. Changes to the electronic and steric properties of the β-N-acyl group were well tolerated; however, small changes to the binding α-N-acyl group were found to significantly affect hydrogenation yields.