Photocatalytic Regioselective Alkylation of 4-Alkenylpyridines via Delocalized Pyridinyl Radicals

The control of selectivity in delocalized radical systems remains a formidable challenge in synthetic chemistry. We report a photocatalytic strategy for the regioselective alkylation of 4-alkenylpyridines using 4-alkyl-1,4-dihydropyridines (alkyl-DHPs) as radical precursors. The reaction proceeds via delocalized pyridinyl radicals, enabling radical–radical cross-coupling that delivers C6-alkylated products with exclusive regioselectivity, contrasting with the C4-selective pathway observed for simple pyridinyl radicals. Mechanistic studies and DFT calculations reveal that reversible formation of an unstable C4-coupled intermediate funnels the reaction toward the thermodynamically favored C6 pathway.