Aerobic C−N Bond Formation through Enzymatic Nitroso‐Ene‐Type Reactions

The biocatalytic oxidation of acylated hydroxylamines enables the direct and selective introduction of nitrogen functionalities by activation of allylic C−H bonds. Utilizing either laccases or an oxidase/peroxidase couple for the formal dehydrogenation of N‐hydroxycarbamates and hydroxamic acids with air as the terminal oxidant, acylnitroso species are generated under particularly mild aqueous conditions. The reactive intermediates undergo C−N bond formation through an ene‐type mechanism and provide high yields both in intramolecular and intermolecular enzymatic aminations. Investigations on different pathways of the two biocatalytic systems and labelling studies provide more insight into this unprecedented promiscuity of classical oxidoreductases as catalysts for nitroso‐based transformations.