Electro/Ni Dual‐Catalyzed Decarboxylative C(sp3)−C(sp2) Cross‐Coupling Reactions of Carboxylates and Aryl Bromide

Abstract Paired redox‐neutral electrolysis offers an attractive green platform for organic synthesis by avoiding sacrificial oxidants and reductants. Carboxylates are non‐toxic, stable, inexpensive, and widely available, making them ideal nucleophiles for C−C cross‐coupling reactions. Here, we report the electro/Ni dual‐catalyzed redox‐neutral decarboxylative C(sp 3 )−C(sp 2 ) cross‐coupling reactions of pristine carboxylates with aryl bromides. At a cathode, a Ni II (Ar)(Br) intermediate is formed through the activation of Ar−Br bond by a Ni I ‐bipyridine catalyst and subsequent reduction. At an anode, the carboxylates, including amino acid, benzyl carboxylic acid, and 2‐phenoxy propionic acid, undergo oxidative decarboxylation to form carbon‐based free radicals. The combination of Ni II (Ar)(Br) intermediate and carbon radical results in the formation of C(sp 3 )−C(sp 2 ) cross‐coupling products. The adaptation of this electrosynthesis method to flow synthesis and valuable molecule synthesis was demonstrated. The reaction mechanism was systematically studied through electrochemical voltammetry and density functional theory (DFT) computational studies. The relationships between the electrochemical properties of carboxylates and the reaction selectivity were revealed. The electro/Ni dual‐catalyzed cross‐coupling reactions described herein expand the chemical space of paired electrochemical C(sp 3 )−C(sp 2 ) cross‐coupling and represent a promising method for the construction of the C(sp 3 )−C(sp 2 ) bonds because of the ubiquitous carboxylate nucleophiles and the innate scalability and flexibility of electrochemical flow‐synthesis technology.