Copper‐Catalyzed C4‐selective Carboxylation of Pyridines with CO2 via Pyridylphosphonium Salts

Abstract Pyridine motifs are widespread pharmacophores in many drugs. Installing various substituents through pyridine C−H bond functionalization is significant for new drug design and discovery. Developments of late‐stage functionalization reactions enrich the strategies for selective functionalization of pyridines. However, late‐stage C−H carboxylation of pyridines is a long‐standing challenge, especially selectively carboxylation with CO 2 on pyridine motifs. Herein, we describe a practical method for C4−H carboxylation of pyridines via one‐pot C−H phosphination and copper‐catalyzed carboxylation of the resulted phosphonium salts with CO 2 . The reaction is conducted under mild conditions and compatible with multiple active groups and several pyridine drugs, providing diverse valuable isonicotinic acid compounds, demonstrating the application potential of this strategy.