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Updated: Oct 1, 2025

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
Published on: July 28, 2022
Biocatalytic One-Carbon Ring Expansion of Aziridines to Azetidines via a Highly Enantioselective [1,2]-Stevens
David C Miller1, Ravi G Lal1, Luca A Marchetti1
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
Abstract:
We report enantioselective one-carbon ring expansion of aziridines to make azetidines as a new-to-nature activity of engineered "carbene transferase" enzymes. A laboratory-evolved variant of cytochrome P450BM3, P411-AzetS, not only exerts unparalleled stereocontrol (99:1 er) over a [1,2]-Stevens rearrangement but also overrides the inherent reactivity of aziridinium ylides, cheletropic extrusion of olefins, to perform a [1,2]-Stevens rearrangement. By controlling the fate of the highly reactive aziridinium ylide intermediates, these evolvable biocatalysts promote a transformation which cannot currently be performed using other catalyst classes.
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