Highly Diastereoselective and Enantioselective Olefin Cyclopropanation Using Engineered Myoglobin‐Based Catalysts

Using rational design, an engineered myoglobin‐based catalyst capable of catalyzing the cyclopropanation of aryl‐substituted olefins with catalytic proficiency (up to 46 800 turnovers) and excellent diastereo‐ and enantioselectivity (98–99.9 %) was developed. This transformation could be carried out in the presence of up to 20 g L −1 olefin substrate with no loss in diastereo‐ and/or enantioselectivity. Mutagenesis and mechanistic studies support a cyclopropanation mechanism mediated by an electrophilic, heme‐bound carbene species and a model is provided to rationalize the stereopreference of the protein catalyst. This work shows that myoglobin constitutes a promising and robust scaffold for the development of biocatalysts with carbene‐transfer reactivity.