Energy-transfer-induced [3+2] cycloadditions of N-N pyridinium ylides

Photocycloaddition is a powerful reaction to enable the conversion of alkenes into high-value synthetic materials that are normally difficult to obtain under thermal conditions. Lactams and pyridines, both prominent in pharmaceutical applications, currently lack effective synthetic strategies to combine them within a single molecular structure. Here we describe an efficient approach to diastereoselective pyridyl lactamization via a photoinduced [3+2] cycloaddition, based on the unique triplet-state reactivity of N-N pyridinium ylides in the presence of a photosensitizer. The corresponding triplet diradical intermediates allow the stepwise radical [3+2] cycloaddition with a broad range of activated and unactivated alkenes under mild conditions. This method exhibits excellent efficiency, diastereoselectivity and functional group tolerance, providing a useful synthon for ortho-pyridyl ?- and d-lactam scaffolds with syn-configuration in a single step. Combined experimental and computational studies reveal that the energy transfer process leads to a triplet-state diradical of N-N pyridinium ylides, which promotes the stepwise cycloaddition.

Automated summary

Photocycloaddition is an efficient reaction that allows the conversion of alkenes into high-value synthetic materials under thermal conditions. In this study, a diastereoselective pyridyl lactamization was achieved through a photoinduced [3+2] cycloaddition using the reactivity of N-N pyridinium ylides, which can form triplet diradical intermediates and undergo stepwise radical cycloaddition with a broad range of alkenes. This method shows excellent efficiency, diastereoselectivity, and functional group tolerance, providing a useful synthon for the synthesis of ortho-pyridyl β- and δ-lactam scaffolds in a single step.