Photocatalytic Pyridylation of Cyanopyridines With Benzyl and Alkyl Dihydropyridines: Divergent Reactivity and Mechanistic Insights

The divergent reactivity of benzyl‐ and alkyl‐substituted 1,4‐dihydropyridines (DHPs) in the photocatalytic pyridylation of cyanopyridines has been investigated. A visible‐light‐ and sunlight‐driven coupling protocol was developed, providing a practical transition‐metal‐free route to C4‐alkyl pyridines with broad substrate scope, gram‐scale applicability, and utility in the synthesis of Ifenprodil. Mechanistic studies revealed that benzyl and alkyl DHPs require distinct photocatalyst/solvent combinations for efficient coupling. Cyclic voltammetry measurements established a redox‐matching model that governs substrate compatibility, while Jiang's dual‐parameter Hammett analysis identified fragmentation of the DHP radical cation as the turnover‐limiting step. These findings provide new mechanistic insight into DHP‐mediated photoredox transformations and offer a useful framework for understanding and predicting the reactivity of DHP‐derived radical processes.