Peroxidase-induced C-N bond formation via nitroso ene and Diels-Alder reactions.

The formation of new carbon-nitrogen bonds is indisputably one of the most important tasks in synthetic organic chemistry. Here, nitroso compounds offer a highly interesting reactivity that complements traditional amination strategies, allowing for the introduction of nitrogen functionalities via ene-type reactions or Diels-Alder cycloadditions. In this study, we highlight the potential of horseradish peroxidase as biological mediator for the generation of reactive nitroso species under environmentally benign conditions. Exploiting a non-natural peroxidase reactivity, in combination with glucose oxidase as oxygen-activating biocatalyst, aerobic activation of a broad range of N -hydroxycarbamates and hydroxamic acids is achieved. Thus both intra- and intermolecular nitroso-ene as well as nitroso-Diels-Alder reactions are performed with high efficiency. Relying on a commercial and robust enzyme system, the aqueous catalyst solution can be recycled over numerous reaction cycles without significant loss of activity. Overall, this green and scalable C-N bond-forming strategy enables the production of allylic amides and various N-heterocyclic building blocks utilizing only air and glucose as sacrificial reagents.