Formal meta-Selective C–H Acylation of Pyridines via the Triplet State of Oxazinopyridine Intermediates

Abstract

Pyridines are privileged structural motifs in pharmaceuticals and bioactive molecules. The introduction of substituents or functional groups at the meta-position via direct C–H functionalization of pyridines remains a formidable challenge. Herein, we report meta-selective acylation and sulfonylation of pyridines via an energy transfer (EnT) process, that activates oxazinopyridine intermediates via the triplet state. This strategy leverages the high reducibility of photoexcited oxazinopyridines, enabling the single-electron reduction of persistent radical precursors such as acyl and sulfonyl azolium salts. Mechanistic investigations, including photophysical experiments and DFT calculations, delineate the generation of the key triplet intermediate and elucidate a cooperative radical coupling pathway. This reaction paradigm overcomes the previous limitation to electrophilic or transient radical partners, providing a versatile platform for diverse meta-functionalizations of pyridine derivatives.