Photosensitization Enables Pauson-Khand-type Reactions with Nitrenes

The Pauson-Khand reaction was invented in 1971, and is one of the most common pericyclic reactions in chemistry featuring the reaction of two unsaturated bonds and carbon monoxide. Even 50 years after its discovery, it remains limited to carbon monoxide as a C1 building block. Herein we report pericyclic reactions with nitrenes as a N1 unit. The reaction that comprises a non-conjugated diene and a nitrene precursor allows the rapid synthesis of bicyclic bioisosteres for common saturated heterocycles such as piperidine, morpholine, piperazine. This is achieved by relaying the diradical nature of triplet nitrene as shown experimentally and computationally. We exemplified this approach in two protocols, late-stage functionalization of drugs, and the application in drug discovery for inhibitors of soluble epoxide hydrolase.