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

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.