Traceless Nucleophile Strategy for C5‐Selective C−H Sulfonylation of Pyridines

Abstract The functionalization of pyridines is crucial for the rapid construction and derivatization of agrochemicals, pharmaceuticals, and materials. Conventional functionalization approaches have primarily focused on the ortho ‐ and para ‐positions, while achieving precise meta‐selective functionalization, particularly at the C5 position in substituted pyridines, remains a formidable challenge due to the intrinsic electronic properties of pyridines. Herein, we present a new strategy for meta ‐ and C5‐selective C−H sulfonylation of N ‐amidopyridinium salts, which employs a transient enamine‐type intermediate generated through a nucleophilic addition to N ‐amidopyridinium salts. This process harnesses the power of electron donor‐acceptor complexes, enabling high selectivity and broad applicability, including the construction of complex pyridines bearing valuable sulfonyl functionalities under mild conditions without the need for an external photocatalyst. The remarkable C5 selectivity, combined with the broad applicability to late‐stage functionalization, significantly expands the toolbox for pyridine functionalization, unlocking access to previously unattainable meta ‐sulfonylated pyridines.