Triplet Energy Transfer-Mediated Intermolecular Paternò-Büchi Reaction for the Synthesis of Trifluoromethylated Oxetanes.

Oxetanes are increasingly used as compact, polar carbonyl (bio)isosteres in drug discovery, and the combination with a trifluoromethyl group enables fine-tuning of molecular properties. Here, we report a visible-light-mediated Paternò-Büchi strategy that accesses CF3-containing oxetanes via triplet-energy-transfer activation and delivers a broad range of CF3-containing oxetane products with excellent regio- and diastereoselectivity. Mechanistic studies indicate that although sensitization of both the alkene and carbonyl occurs in solution, the subsequent stepwise [2 + 2] cycloaddition proceeds preferentially from the triplet excited state of the CF3-substituted carbonyl partner.