Triplet−Triplet Energy Transfer Photocatalysis Enabled meta-C−H Functionalization of Pyridines

Dearomatization–rearomatization has emerged as an increasingly powerful strategy for achieving meta-selective C−H functionalization of pyridines—a transformation that is as synthetically important as it is challenging. Existing methods are mechanistically unified by their reliance on ground-state dearomatized intermediates, which are intercepted by electrophiles or transient electrophilic radicals. We now disclose a conceptually distinct activation mode that circumvents this paradigm: energy-transfer photocatalysis generates excited triplet oxazinopyridines, providing efficient access to valuable metaalkylated pyridines. This triplet manifold overcomes the key obstacle that direct photosensitization of pyridines is unfeasible owing to their prohibitively high triplet energy. Combined experimental and computational studies substantiate a triplet–triplet energy transfer mechanism and establish this as a mechanistically discrete pathway for pyridine meta-functionalization. This transition-metal-free protocol features perfect regiocontrol, broad functional group tolerance, and applicability to late-stage functionalization of pharmaceuticals.