Palladium-Catalyzed Cascade Distal C–H Methylation and Cyclization for the Construction of Spirooxindole Skeletons

Abstract

Transition metal-catalyzed C–H methylation represents a straightforward approach for introducing methyl groups into organic molecules. Herein, we report a palladium-catalyzed alkene-relayed remote C–H methylation reaction that utilizes dimethyl carbonate as the methylation reagent. The aryl groups distal to a bromo group were dimethylated via C–H activation, leading to the formation of spirooxindoles as the final products through C(sp³)–H activation and C(sp³)–C(sp³) coupling. This cascade process involves the formation of four C–C bonds and the activation of three C–H bonds. The reaction not only provides a new approach to C–H methylation but also offers a novel method for constructing spirooxindole skeletons by merging skeleton construction and methylation into a single step.