Palladium‐Catalyzed Chemoselective Amination of Chloro(hetero)aryl Triflates Enabled by Alkyl‐Pyrazole‐Based Phosphine Ligands

Abstract This study describes the palladium‐catalyzed chemoselective amination of chloro(hetero)aryl triflates in the C−Cl bond for the first time. A newly designed and synthesized alkyl‐pyrazole‐based phosphine ligand, L26 ( BirdPhos ), which is featured with the pyrazole ligand core and the cyclohexyl group at the C3 and C5 positions, was key to the success of this reaction. A variety of chloro(hetero)aryl triflates coupled with aromatic, aliphatic, and heterocyclic amines smoothly afforded the corresponding products up to 97% yields with general chemoselectivity (>99%) in the C−Cl bond. Drug analogs were also synthesized via the chemoselective intermolecular amination. This study attempts to investigate the structure‐activity relationship of this new class of ligand through experimental and density functional theory (DFT) calculations.