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

Abstract

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.