Room-Temperature Palladium-Catalyzed Aminative Suzuki–Miyaura Coupling of Arylthianthrenium Salts and Mechanistic Studies

The development of novel catalytic transformations that repurpose classical reagents to directly access structurally diverse products from the same starting materials has garnered significant interest. By eliminating the need to separately synthesize and purify new reagents, the chemical space reachable from existing functionalized intermediates can be increased multifold. Nitrogen insertion strategies can convert the C-C bond formed in traditional Suzuki-Miyaura coupling into a C-N-C bond, substantially expanding the explorable chemical space. Herein, building upon the arylthianthrenium salt strategy, we have developed a room-temperature palladium-catalyzed nitrogen-atom insertion coupling reaction, providing a new retrosynthetic disconnection strategy that can be directly applied to the late-stage functionalization (LSF) of complex drug molecules. Notably, this intermolecular three-component aminative coupling proceeds smoothly at room temperature, which not only aligns with the principles of green chemistry by obviating the need for heating apparatus and light-irradiation equipment, but also reduces energy consumption while enhancing reaction safety. To probe the mechanism, control experiments were conducted, and the catalytic reaction was monitored by NMR spectroscopy. Based on these results and density functional theory (DFT) calculations, the barrier for the overall rate-determining step is only 16.5 kcal/mol, explaining the room-temperature reactivity.