Enantiomerically Enriched Aziridine-2-carboxylates via Copper-Catalyzed Reductive Kinetic Resolution of 2H-Azirines

Abstract

We present the first reductive kinetic resolution of racemic 2H-azirines to prepare optically enriched N-H aziridine-2-carboxylates, which are bench stable and easily diversifiable building blocks, concomitantly with the corresponding enantiomerically enriched 2H-azirines. The N-H aziridines were obtained with excellent diastereoselectivity (>20:1) and high enantioselectivity (up to 94%). A Hammett study revealed a linear free energy relationship between the ΔΔG⧧ of the diastereomeric transition states and the σp- values. DFT calculations and non-covalent interaction analysis suggested that non-classical H–bonding interactions and edge-to-face aromatic interactions between the substrate and the ligand are responsible for the stereoselectivity and also for the substrate electronic effects observed in the Hammett study.