C–H Pyridonation of (Hetero-)Arenes by Pyridinium Radical Cations

Abstract

Pyridones are important heteroaromatic scaffolds found in natural products and pharmaceuticals and are, therefore, of major interest in organic synthetic chemistry. Here we report the first C–H pyridonation of unactivated (hetero-)­arenes, providing a methodology to directly access N-aryl-2- and 4-pyridones. Generation of pyridinium radical cations through single-electron reduction allows for the synthesis of pyridones on structurally complex molecules.

Pyridinium Salts as Redox‐Active Functional Group Transfer Reagents

“…On the basis of their previous studies,R itter and coworkers later found that the use of N-trifloxypyridinium salts bearing chloride in the 2-or 4-position enables the installation of 2-and 4-pyridones on (hetero-)arenes through ao ne-pot, two-step procedure involving C À Hf unctionalization by the radical cation and subsequent hydrolysis. [99]…”

Late stage C–H functionalization via chalcogen and pnictogen salts

“…Based on earlier work, Ritter subsequently developed a onepot, two-step, direct C-H pyridonation of (hetero-)arenes using chloropyridinium radical cations. 23 This approach enables an unprecedented net C-H functionalization of an arene with the nitrogen atom of a pyridone under mild conditions. Pyridones are challenging substrates because of their low nucleophilicity and ambidentate nature but oen appear in therapeutic molecules and in SAR studies.…”

Recent Advances in Photocatalytic C–N Bond Coupling Reactions

“…Recently, Ritter and co-workers developed an interesting C-H pyridonation reaction which successfully coupled 2-or 4-pyridones to arenes (Scheme 29). 34 Photoredox catalysis generates chloropyridinium radical cations for coupling to arenes to furnish N-arylpyridones in excellent yields. Late-stage modification of natural compounds was also realized by this method.…”