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

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.