Mechanistic Investigation Of Palladium-Catalyzed Amidation Of Aryl Halides

A mechanistic investigation with the Becke3 LYP density functional theory(DFT)has been carried out on the palladium-catalyzed amidition of bromobenzene and tBu-isocyanide.The major research contents are as follows:In the first part,we mainly introduce the traditional coupling reactions,the emerging coupling reactions,the selected topic background,and research significance of the palladium-catalyzed coupling reaction.In the second part,we simply introduced the involved theoretical basis and computational method when calculating the palladium-catalyzed amidition of bromobenzene and tBu-isocyanide.In the third part,a systematic theoretical study is performed on palladium-catalyzed amidation of aryl halides.Six possible pathways(three monophosphine and three bisphosphine pathways)for amidation in our hypothetical reaction mechanism are raised in this article.The whole catalytic cycle consists of five steps: oxidative addition,migratory insertion,anion exchange,reductive elimination,and hydrogen migration.In the oxidative addition reaction,we put forward four possible reaction pathways(two monophosphine and two bisphosphine pathways).The computational results show that monophosphine compound PdL as a catalyst has a lower Gibbs free energy.Like most of the palladium-catalyzed coupling reaction,the rate-determining step is oxidative addition with a small Gibbs free energy of 14.6 kcal/mol.In the migratory insertion step,it is mainly divided into three situations that tBu-isocyanide inserts into the ortho Pd-C and Pd-O bonds,and para Pd-C bond.However,there is a lowest energy barrier 14.2 kcal/mol when tBu-isocyanide inserts into the ortho Pd-C bond.tBu-isocyanide provides an important source which includes carboxy and amino groups to establish amide group.For anion exchange,it is suggested that path 1a is the most favorable pathway with the help of the base.In order to prove the effect of CsF,we calculate the situation that there is no CsF involved in.In this reaction,water as a nucleophilic reagent attacks compounds 5.Calculation results show that reaction energy barrier is too high to happen.At the same time,it is also proved that water in the solution provides a source of oxygen.Our hypotheses are in wonderful line with experimental observations.Finally,in the hydrogen migration step,two possible reaction mechanisms are raised: the four-membered ring mechanism and the six-membered ring mechanism.Due to the assisting influence of water,it is illustrated that six-membered ring path is the energetically favored.In addition,our calculations indicate that dimethyl sulfoxide as solvent doesn't change the rate-determining step.