Asymmetric Syntheses of Aziridine-2-carboxylates via Reductive Kinetic Resolution of 2H-Azirines

Enantioenriched aziridine-2-carboxylates are valuable organic compounds thanks to their versatility as chiral building blocks. Several syntheses of bioactive molecules employ aziridine-2-carboxylates as a crucial synthetic intermediate, e.g. the total synthesis of dynobacin A. However, traditional strategies only access N-protected aziridines, which are poorly stable and can undergo unwanted side reactions as ring-opening. Herein, we present the first copper hydride kinetic resolution of racemic 2H-azirines for the asymmetric preparation of N-H aziridine-2-carboxylates and the corresponding enantioenriched 2H-azirines. This is relevant as N-H aziridine-2-carboxylates are a generally bench stable and easily diversifiable building block. After an extensive catalyst screening and reaction optimization, the N-H aziridines were obtained with excellent diastereoselectivity (>20:1) and high enantioselectivity (up to 94%). Additionally, we conducted a Hammett study and we observed a linear free energy relationship between the ΔΔG⧧ of the diastereomeric transition states and the σp- values.