Mechanochemical Generation of Active Pd/BippyPhos Catalyst for Efficient C–N Cross‐Coupling in Air

• DOI: 10.1002/cssc.202500545
• Publication Date: 2025-04-07T15:34:43Z
• Authors: Deniz Karabiyikli; Alexandre Saad; Sokaina Hammoud; Severine Schneider; Romuald Manca; Jesus Raya; Martine Schmitt; Frederic Bihel
• Keywords: Inert gas; Coupling reaction; Organic Synthesis

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 typically require organic solvents inert atmospheres, such argon, increasing environmental, health, safety (EHS) concerns. Using electron‐rich bulky phosphine ligands combination with [Pd(π‐cinnamyl)Cl]₂, we generate a highly active palladium catalyst capable of achieving efficient C–N bond formation the solid state. Remarkably, while previous studies showed that this palladium–phosphine complex occurs only protic water or alcohols, but not classical solvents, demonstrate its generation absence any solvent, confirmed solid‐state ³¹P NMR, supporting role catalytic species.. This process enables coupling broad range aryl bromides chlorides amines, anilines, amides, carbamates, ureas, delivering good to excellent yields. mechanochemical method operates minimal loading proceeds efficiently air, offering practical sustainable alternative traditional solution‐phase reactions.