Theoretical Study On The Mechanism Of Palladium-Catalyzed Allyl Amination

Allylamine compounds are an important class of nitrogen-containing compounds,which not only are used as organic intermediates but also are widely applied to synthesis heterocyclic compounds.Moreover,the allylamine compounds have significant pharmacological activity against skin and nail infections caused by superficial fungi.Therefore,developing a simple and efficient synthesis method of allylamine compounds has important practical significance.In this paper,we have carried out the density functional theory?DFT?B3LYP method to investigate the reaction mechanism of palladium-catalyzed allyl amination in detail.The major research contents are separated into three parts:The first part briefly introduces the various methods for the synthesis of nitrogen-containing derivatives of olefins and theoretical research progress of palladium-catalyzed amination reaction.The second part introduces the basic theoretical knowledge of the calculation methods,including the ab initio self-consistent field method,density functional theory,and the solvation effect.In the third part,the detailed mechanism of the Pd catalyzed synthesis reaction of allylamine derivatives with allylbenzene and quinazolinone has been studied.According to the possible form of catalyst in the allyl amination reaction,we proposed two mechanisms of PdCl₂ dimer mechanism and PdCl₂ monomer mechanism.In the mechanism of PdCl₂ dimer,we studied mechanism A and mechanism B.In the mechanism A,path 1 involving two molecules of allylbenzene to participate reaction and path 2 involving one molecule of allylbenzene to participate reaction are evaluated.The path 1 is mainly divided into five steps:C-H activation,C'-H activation,N-H activation,reduction elimination,and catalyst regeneration.In path 2,four steps are included:C-H activation,N-H activation,reduction elimination,and catalyst regeneration.The N-H activation step in two paths destroys the Pd-Cl-Pd bridge bond,resulting in a high reaction energy barrier.Therefore,we propose mechanism B.Four steps in mechanism B are involved:C-H activation,N-H activation,C-N coupling,?-H elimination,and catalyst regeneration.The results indicate that C-N coupling is the rate-determining step and the reaction energy barrier is 39.3 kcal/mol.In addition,it is found that the coordination of the?³-allyl group can effectively reduce the energy of the reaction.In summary,mechanism B is more favorable than mechanism A in the PdCl₂ dimer mechanism.In the PdCl₂ monomer mechanism,two types of reaction mechanisms are proposed.They differ in the sequence of allylbenzene activation versus quinazolinone activation with the catalyst PdCl₂.The calculations show that the energy barriers of mechanism A-1 and mechanism B-1 are 58.1 kcal/mol and 54.4 kcal/mol,respectively.By comparing the PdCl₂ dimer mechanism and the PdCl₂ monomer mechanism,the mechanism B in the PdCl₂ dimer mechanism is more favored both kinetically and thermodynamically than the two mechanisms in the PdCl₂ monomer mechanism.The mechanism B is the optimal mechanism of the reaction system.