Enantioselective synthesis of amino acids from ammonia

• Published in: Nature catalysis Vol. 5; no. 6; pp. 571 - 577
• Main Authors: Li, Mao-Lin, Pan, Jia-Bin, Zhou, Qi-Lin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.06.2022
• Subjects: Amino acids; Ammonia; Asymmetry; Basicity; Copper; Copper compounds; Efficiency; Enantiomers; Energy; Equilibrium; Esters; Hydrogen; Hydrogen bonds; Lewis base; Ligands; Nitrogen; Protons; Synthesis
• ISSN: 2520-1158
• DOI: 10.1038/s41929-022-00779-2

Metal-catalysed reactions involving ammonia gas are plagued by ammonia’s strong Lewis basicity, which leads to poor chemoselectivity and enantioselectivity. Here we introduce a strategy for preparing chiral α-amino acids directly from ammonia. By the cooperative action of copper complexes and chiral hydrogen-bond donors, enantioselective insertion of carbenes into the N–H bond of ammonia can construct C–N bonds in excellent yield and enantioselectivity. Using this method, we coupled a wide variety of diazoesters with ammonia to produce natural and non-natural chiral α-amino acids, which have a wide range of applications in pharmaceutical and biochemistry research. Our work provides a general method for asymmetric transformations involving ammonia.The use of ammonia as a nitrogen source in catalytic asymmetric reactions is attractive but represents a difficult exercise. Now, the asymmetric synthesis of N-unprotected α-amino esters from α-diazoesters and ammonia is achieved by cooperative action of copper complexes and chiral hydrogen-bond donors.