meta ‐Methylation of Aniline and Anisole Derivatives via Palladium/S, O‐Ligand/Norbornene Cooperative Catalysis

The introduction of methyl groups into drug candidates is a widely used strategy in medicinal chemistry to improve pharmaceutical properties. However, the introduction of methyl groups to the meta ‐position of electron‐rich arenes is a key challenge, since it is complementary to the natural reactivity in electrophilic aromatic substitutions and therefore mostly relies on prefunctionalized substrates or directing groups. Herein, we disclose a selective meta ‐CH methylation of anilines and anisole derivatives that eliminates the need for less step‐economical prefunctionalization strategies, enabled by a Pd/S, O‐ligand/norbornene cooperative catalytic system with the potential for modification and isotope labeling of drug candidates and natural products.