Conspectus The radical-mediated C–H functionalization of pyridines has attracted considerable attention as a powerful tool in synthetic chemistry for the direct functionalization of the C–H bonds of the pyridine scaffold. Classically, the synthetic methods for functionalized pyridines often involve radical-mediated Minisci-type reactions under strongly acidic conditions. However, the site-selective functionalization of pyridines in unbiased systems has been a long-standing challenge because the pyridine scaffold contains multiple competing reaction sites (C2 vs C4) to intercept free radicals. Therefore, prefunctionalization of the pyridine is required to avoid issues observed with the formation of a mixture of regioisomers and overalkylated side products. Recently, N-functionalized pyridinium salts have been attracting considerable attention in organic chemistry as promising radical precursors and pyridine surrogates. The notable advantage of N-functionalized pyridinium salts lies in their ability to enhance the reactivity and selectivity for synthetically useful reactions under acid-free conditions. This approach enables exquisite regiocontrol for nonclassical Minisci-type reactions at the C2 and C4 positions under mild reaction conditions, which are suitable for the late-stage functionalization of bioactive molecules with greater complexity and diversity. Over the past five years, a variety of fascinating synthetic applications have been developed using various types of pyridinium salts under visible light conditions. In addition, a new platform for alkene difunctionalization using appropriately designed N-substituted pyridinium salts as bifunctional reagents has been reported, offering an innovative assembly process for complex organic architectures. Intriguingly, strategies involving light-absorbing electron donor–acceptor (EDA) complexes between pyridinium salts and suitable electron-rich donors further open up new reactivity under photocatalyst-free conditions. Furthermore, we developed enantioselective reactions using pyridinium salts to afford enantioenriched molecules bearing pyridines through single-electron N-heterocyclic carbene (NHC) catalysis. Herein, we provide a broad overview of our recent contributions to the development of N-functionalized pyridinium salts and summarize the cornerstones of organic reactions that successfully employ these pyridinium salts under visible light conditions. The major advances in the field are systematically categorized on the basis of the pyridines’ N-substituent, N–X (X = O, N, C, and SO2CF3), and its reactivity patterns. Furthermore, the identification of new activation modes and their mechanistic aspects are discussed by providing representative contributions to each paradigm. We hope that this Account will inspire broad interest in the continued innovation of N-functionalized pyridinium salts in the exploration of new transformations.

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Herein we report a practical protocol for the visible-light-induced regiodivergent radical hydropyridylation of unactivated alkenes using pyridinium salts. This approach provides a unified synthetic platform to control the regioselectivity of the synthesis of linear or branched C4-alkylated pyridines. A remarkable selectivity switch from the anti-Markovnikov to the Markovnikov product can be achieved by the addition of tetrabutylammonium bromide. The versatility of this protocol is further demonstrated based on the late-stage functionalization in pharmaceuticals.