Universal Cis-Trans Aziridinations

By swapping their starting material’s ester functional group with an amide, chemists at Michigan State University have managed to switch a previously reported aziridination reaction’s diastereoselectivity from cis to trans (J. Am. Chem. Soc., DOI: 10.1021/ja1038648). The trans aziridination reaction, discovered by William D. Wulff and Aman A. Desai, makes use of the same imine starting material and the same chiral boroxinate catalyst as was previously reported by Wulff’s group for cis aziridinations. But instead of using a diazoester as the reactive nucleophile, Wulff and Desai use a diazoacetamide, which gives them completely different stereoselectivity. Taken together, the two reactions provide “an unprecedented universal catalytic asymmetric aziridination protocol,” according to the researchers. Along with Mathew J. Vetticatt, of New York’s Albert Einstein College of Medicine, Wulff and Desai used density functional theory calculations to study the mechanism behind this unique switch in diastereoselectivity. They found that hydrogen bonding between the amidic hydrogen of the diazoacetamide and an oxygen atom of the chiral catalyst is responsible for the reversal (J. Am. Chem. Soc., DOI: 10.1021/ja103863j).