Asymmetric Synthesis of Aziridines from Diazoacetamides and N-Boc Imines

Significance

An enantioselective synthesis of trans-substituted aziridines 3 from N-Boc imines 1 and diazoacetamides 2 is presented under chiral Brønsted acid catalysis. A range of dicarboxylic acid catalysts bearing different 3,3-diaryl groups were screened, with the 3,3-dimesityl-substituted diacid 4 providing the highest enantioinduction. Although tertiary amides were found to be inert under the reaction conditions, treatment of N-aryl diazoacetamides 2 with N-Boc imines 1 in the presence of 5 mol% catalyst gave exclusively the trans-aziridines 3 in poor to excellent yield and with excellent enantioselectivity. Higher yields were obtained with electron-neutral and -rich aryl imines, however, both electron-donating and -withdrawing groups were tolerated on the acet­amide component. The trans stereochemistry of the aziridine ring was unambiguously established by X-ray crystallography.