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

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.