A New Type of Stereoselectivity in Baeyer–Villiger Reactions: Access to E ‐ and Z ‐Olefins

A new concept for accessing configurationally defined trisubstituted olefins has been developed. Starting from a common ketone precursor of the type 4‐ethylidenecyclohexanone, Baeyer–Villiger monooxygenases are employed as catalysts in diastereoselective Baeyer–Villiger reactions leading to the corresponding E ‐ or Z ‐configurated lactones. Wild‐type cyclohexanone monooxygenase (CHMO) as catalyst delivers the E ‐isomers and a directed evolution mutant the opposite Z ‐isomers. Subsequent transition metal‐catalyzed chemical transformations of a key product containing a vinyl bromide moiety provide a variety of different trisubstituted E‐ or Z‐ olefins. A model based on QM/MM sheds light on the origin of this unusual type of diastereoselectivity. In contrast to this biocatalytic approach, traditional Baeyer–Villiger reagents such as m ‐CPBA fail to show any selectivity, 1:1 mixtures of E ‐ and Z ‐olefins being formed.