Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones

Here we present an effective nickel‐catalyzed carbonylative cross‐coupling for direct access to alkyl aryl ketones from readily accessible redox‐activated tetrachlorophthalimide esters and aryl boronic acids. The methodology, which is run employing only 2.5 equivalents of CO and simple Ni(II) salts as the metal source, exhibits a broad substrate scope under mild conditions. Furthermore, this carbonylation chemistry provides an easy switch between isotopologues for stable (13CO) and radioactive (14CO) isotope labeling, allowing its adaptation to the late‐stage isotope labeling of pharmaceutically relevant compounds. Based on DFT calculations as well as experimental evidence, a catalytic cycle is proposed involving a carbon‐centered radical formed via nickel(I)‐induced outer‐sphere decarboxylative fragmentation of the redox‐active ester. The development of an effective nickel‐catalyzed carbonylative cross coupling of redox‐activated alkyl carboxylic acids and aryl boronic acids is presented. A wide variety of alkyl aryl ketones is obtained in good yields, and the chemistry is easily applicable to stable and radiocarbon isotope labeling. The mechanism of the transformation has been investigated applying experimental and DFT methods.