Mechanochemistry-Directed Ligand Design: Development of a High-Performance Phosphine Ligand for Palladium-Catalyzed Mechanochemical Organoboron Cross-Coupling

Mechanochemical synthesis with transition-metal catalysts has attracted significant attention because of its numerous advantages, including reduced solvent waste, shorter reaction times, and the avoidance of problems posed by low solubility of starting materials. However, despite the fact that mechanochemical reaction environment is largely different from that of homogeneous solution systems, transition-metal catalysts originally developed for solution-based conditions have also been diverted to mechanochemical reactions without molecular-level devices suitable for mechanochemistry, which limits further development of more efficient mechanochemical cross-coupling processes. Here the author reports the conceptually distinct, mechanochemistry-directed ligand design for palladium-catalyzed Suzuki–Miyaura cross-coupling reaction using ball milling. The ligand development was guided by the experimental observation of catalyst deactivation associated with aggregation of palladium species, which was particularly prominent in solid-state reactions. By introducing a flexible polyethylene glycol (PEG) chain into the ligand backbone, the author found that phosphine-ligated palladium (0) species could be efficiently immobilized in the fluid amorphous phase created by the PEG chains, preventing the catalyst kneading into the crystalline solid phase and the undesired aggregation-induced catalyst deactivation. This new mechanochemistry-directed catalytic system showed high catalytic activity at near room temperature for the reactions of solid polyaromatic substrates that usually require elevated temperature when previous catalysts with ligands commonly used in solution reactions (e.g., SPhos) were employed. The present study provides important perspectives for the rational design of high-performance transition-metal catalysts that potentially inspire the development of industrially attractive, solvent-less mechanochemical cross-coupling technologies.