Mechanochemical Generation of Active Pd/BippyPhos Catalyst for Efficient CN Cross‐Coupling in Air

Carbonnitrogen (CN) bond-forming cross-coupling reactions catalyzed by palladium-based systems, known as Buchwald-Hartwig aminations, are widely used in natural product synthesis, pharmaceuticals, agrochemicals, and materials science. However, these reactions typically require organic solvents and inert atmospheres, such as argon, increasing environmental, health, and safety concerns. Using electron-rich bulky phosphine ligands in combination with [Pd(π-cinnamyl)Cl]₂, a highly active palladium catalyst capable of achieving efficient CN bond formation in the solid state is generated. Remarkably, while previous studies showed that the formation of this palladium-phosphine complex occurs only in protic solvents such as water or alcohols, but not in classical organic solvents, its generation in the absence of any solvent is demonstrated, as confirmed by solid-state ³ ¹P nuclear magnetic resonance, supporting its role as the active catalytic species. This process enables the coupling of a broad range of aryl bromides and chlorides with amines, anilines, amides, carbamates, or ureas, delivering good to excellent yields. This mechanochemical method operates with minimal palladium loading and proceeds efficiently in air, offering a practical and sustainable alternative to traditional solution-phase reactions.