Myoglobin‐Catalyzed Olefination of Aldehydes

AbstractThe olefination of aldehydes constitutes a most valuable and widely adopted strategy for constructing carbon–carbon double bonds in organic chemistry. While various synthetic methods have been made available for this purpose, no biocatalysts are known to mediate this transformation. Reported herein is that engineered myoglobin variants can catalyze the olefination of aldehydes in the presence of α‐diazoesters with high catalytic efficiency (up to 4,900 turnovers) and excellent E diastereoselectivity (92–99.9 % de). This transformation could be applied to the olefination of a variety of substituted benzaldehydes and heteroaromatic aldehydes, also in combination with different alkyl α‐diazoacetate reagents. This work provides a first example of biocatalytic aldehyde olefination and extends the spectrum of synthetically valuable chemical transformations accessible using metalloprotein‐based catalysts.