Mechanistic analysis of N-arylation with diaryliodonium salts

Diaryliodonium salts are novel reagents for organic synthesis, especially for the arylation of heteroatom nucleophiles which generates pharmaceutically relevant products. The generally accepted mechanism for these reactions is based on kinetic studies that are three quarters of a century old and do not reflect the modern reaction conditions that have been developed over the past two decades-long boom in diaryliodonium salts chemistry. Here, we provide a detailed kinetic analysis of the phenylation of a tertiary amine nucleophile using modern tools of kinetic analysis, variable time normalisation analysis (VTNA), as well as temperature dependent analysis of dynamics (van’t Hoff and Arrhenius analysis). We quantify the kinetic relevance of both counter anions and aryl “dummy” ligands, and Density Functional Theory (DFT) and Natural Bond Orbital (NBO) theory provide new insight into the role that frontier orbitals on iodine play in the ligand coupling step.