Palladacycle Catalyst Based on a Cyclopropane Monophosphine Ligand for the Suzuki–Miyaura Cross-Coupling Reaction

The Suzuki–Miyaura cross-coupling reaction is widely used in organic synthesis. However, its reactivity and selectivity remain unsatisfactory for some functionalized substrates, and the synthetic efficiency for many functional molecules urgently needs improvement. Developing palladium catalysts compatible with this reaction to address these challenges and expand its practical applications holds significant research value. This paper reports a divalent palladacycle complex catalyst based on the cyclopropane monophosphine ligand TPhos and systematically investigates its application in the Suzuki–Miyaura cross-coupling reaction. Studies show that this catalyst exhibits exceptionally high reactivity, with a maximum turnover number (TON) of up to 192,000, along with excellent functional group tolerance. Notably, for substrates containing reactive functional groups such as alkenyl, alkynyl, and aldehyde groups, it effectively suppresses competitive side reactions such as Heck coupling, Sonogashira coupling, and disproportionation, thereby yielding the desired cross-coupled products with high chemoselectivity. Furthermore, the catalytic system developed herein was successfully applied to the gram-scale synthesis of various pharmaceutical intermediates, demonstrating a substantial reduction in catalyst loading compared with literature reports.