Selective meta-C-H Acylation of Pyridines through N-Heterocyclic Carbene and Photoredox Dual Catalysis.

Incorporating an acyl group onto a pyridine ring without preinstalled transformable functional groups is particularly attractive in synthetic and medicinal chemistry. While established methods allow for acylation at ortho- or para-positions, selective meta-C-H acylation remains an unsolved problem. Here, we report a mild protocol for meta-C-H acylation of pyridines via redox-neutral temporary dearomatization. The sequence involves tandem cycloadditive dearomatization, synergistic N-heterocyclic carbene (NHC)/photoredox-catalyzed C-H acylation, and acid-promoted rearomatization. Mechanistic investigations, including experimental studies and density functional theory (DFT) calculations, support a pathway involving the concurrent generation of oxazino-pyridine-derived allylic-type radicals and acyl azolium radicals, followed by their radical-radical cross-coupling.