Biocatalytic One-Carbon Ring Expansion of Aziridines to Azetidines via a Highly Enantioselective [1,2]-Stevens Rearrangement

17 January 2022, Version 3
This content is a preprint and has not undergone peer review at the time of posting.


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.


Asymmetric Catalysis
Directed Evolution
[1.2]-Stevens Rearrangements

Supplementary materials

Supporting Information
Supplementary materials for the manuscript


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