Electroreductive Radical C–C Acylation Coupling from <i>N</i> , <i>N</i> ‐Dimethylamides and Organic Halides via Inert C(O)−N Bond Cleavage: Facile Access to Aryl Ketones

ABSTRACT The conversion of amides to ketones via C(O)−N bond cleavage has attracted significant attention, with cross‐electrophile coupling (XEC) between amides and organic halides emerging as a particularly valuable strategy. However, such transformations have so far been limited to activated amides and transition metal catalysis. The cross‐electrophile coupling acylation of simple N , N ‐dimethylamides via C(O)−N bond cleavage remains challenging due to their higher chemical inertness and lower electrophilicity compared to activated amides. Herein, we report the successful development of an electroreductive cross‐electrophile coupling (eXEC) reaction between N , N ‐dimethylamides and organic halides, which affords ketones through the highly inert C(O)−N bond cleavage. This work establishes an unprecedented electrochemical reduction method for C(O)−N bond cleavage of N,N ‐dimethylamides by single‐electron activation. Extensive experimental and computational studies elucidate the detailed reaction mechanism. The process begins with the single‐electron reduction of the N , N ‐dimethylamide in a lithium‐ion electroreduction system, generating a ketyl radical anion. This key intermediate disrupts the amide resonance, weakening the C(O)−N bond. Consequently, this facilitates the typically challenging radical‐radical cross‐coupling, followed by scission of the C(O)−N bond. The observed selectivity of the cross‐coupling is governed by the combined effects of a thermodynamic preference for coupling and the high concentration disparity between the two distinct radical species.