Work

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

Year: 2024

Type: article

Abstract: 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 ( 13 CO) and radioactive ( 14 CO) 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.

Source: Angewandte Chemie

DOI: 10.1002/ange.202412247