Mechanistic investigation of palladium-catalyzed amidation of aryl halides

A mechanistic investigation using Becke3LYP density functional theory (DFT) was carried out on the palladium-catalyzed amidition of bromobenzene and (t)Bu-isocyanide. The whole catalytic cycle consists of five steps: oxidative addition, migratory insertion, anion exchange, reductive elimination, and hydrogen migration. The rate-determining step is oxidative addition, with a small Gibbs free energy of 14.6 kcal mol(-1). In the migratory insertion step, (t)Bu-isocyanide provides an important source of carboxy and amino groups to establish the amide group. For anion exchange, path 1a is suggested as the most favorable pathway with the help of the base, and water provides a source of oxygen which is perfectly in line with experimental observations. Finally, in the hydrogen migration step, we illustrate that the six-membered ring path is energetically favored due to the assisting influence of water. In addition, our calculations indicate that using dimethyl sulfoxide as a solvent does not change the rate-determining step.