Enantioselective Electrocatalysis for Cross‐Dehydrogenative Heteroarylation with Indoles, Pyrroles, and Furans

Abstract Oxidative cross‐dehydrogenative C−H/C−H functionalizations represent an exemplary approach for synthesizing carbonyl compounds via α‐heteroarylation. Here we present the development of a direct anodic oxidative coupling process between 2‐acylimidazoles and divergent heterocyclic systems including indole, pyrrole, and furan, facilitated by ferrocene‐assisted asymmetric nickel electrocatalysis with high levels of enantioselectivity. Mechanistic investigations indicate that the reaction initially involves the formation of a chiral Ni‐bound α‐carbonyl radical, which is then captured by the heteroarene radical cation via intermolecular stereoselective radical/radical cation coupling. The mild, scalable, and robust reaction conditions allow for a broad substrate scope and excellent functional group tolerance, enabling access to a wide range of chiral hetero‐compounds. The consequential α‐heteroaromatic carbonyl products can potentially be transformed into a plethora of synthetically valuable frameworks, as exemplified by their application in the asymmetric total synthesis of (−)‐COX‐2 inhibitor, (+)‐acremoauxin A, and (+)‐pemedolac.