Electrochemical Synergistic Ni/Co-Catalyzed Carbonylative Cross-Electrophile Coupling of Aryl and Alkyl Halides with CO.

Abstract

Accessing unsymmetric ketones and achieving their carbon isotope labeling are crucial yet challenging tasks in both synthetic and medicinal chemistry. We report here an efficient electrochemical nickel-/cobalt-catalyzed carbonylative cross-electrophile coupling reaction. This method allows for the modular synthesis of a library of unsymmetric ketones from simple building blocks, including aryl halides, alkyl halides, and gaseous CO. The simultaneous use of nickel and cobalt salts as concerted catalysts ensures the high efficiency of this three-component carbonylative coupling. Furthermore, electrochemical reduction avoids the use of stoichiometric reductants, making this protocol more sustainable and attractive. The broad substrate scope and late-stage ¹³C isotope labeling of complex molecules derived from biologically active compounds highlight the practicality of this method.