Cobalt Polypyridyl‐Enabled Highly Regioselective α‐Heteroarylation of <i>N,O</i> ‐Containing Aliphatics Through Photoelectrocatalysis

Abstract The regioselective functionalization of C─H bonds at positions with nearly identical chemical environments remains a pivotal challenge in synthetic chemistry. While conventional hydrogen atom transfer (HAT) strategies dominate current methodologies, their limitations in selectivity drive the pursuit of alternative mechanisms. Here, we report a photoelectrochemically cooperative catalytic system mediated by a polypyridyl cobalt catalyst, enabling highly regioselective α‐heteroarylation of ethers, alcohols, and amides. Unlike previous cobalt‐based systems in which bond formation occurs independently of the cobalt metal center, the catalyst functions as a photocatalyst to directly oxidize substrates via a single‐electron transfer (SET) process. This strategy eschews traditional HAT pathways, achieving exclusive α‐site selectivity for most substrates while exhibiting broad adaptability to diverse heteroarenes. Subsequent derivatization studies, including oxidation, hydrolysis, reduction, and chloromethylation, validate the synthetic utility for accessing pharmaceutical intermediates.