We report enantioselective one-carbon ring expansion of aziridines to make azetidines as a new, abiologcal activity of engineered 'carbene transferase' enzymes. A laboratory-evolved variant of cytochrome P450BM3, P411-AzetS, not only overrides the inherent reactivity of aziridinium ylides to undergo cheletropic extrusion of ethylene, it also exerts unparalleled stereocontrol (99:1 er) over a [1,2]-Stevens rearrangement, a notoriously challenging reaction class for asymmetric catalysis. These

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... recedented selectivities enable an entirely new strategy for the synthesis of chiral azetidine products from readily available synthetic precursors. The utility of this reaction is highlighted by the synthesis of an enantiopure azetidine on gram scale. The exquisite selectivity of the enzyme enables new-to-nature ring-expansion chemistry that overcomes a longstanding synthetic problem. Figure 1: Classification of enzyme-mediated carbene transfer reactions for various bond disconnections.