Mechanism Study Of Palladium-Catalyzed Chloromethylnaphthalene Dearomatization Reaction

Aliphatic carbocycles are skeleton structure of many medical and natural products. The synthesis of carbocycles is complicated when traditional chemical methods were employed. However, only one step is needed when dearomatization reaction is used, the dearomatization of aromatic compounds with nitrogen-containing can not only synthesize aliphatic carbocycles, but also we can gain arylamines via further functionazation of dearomatization products. Although experimental research of this kind of reaction is active, theoretical research is relatively lagging. Some transition states are short-time living during reaction process, so predicting reaction mechanism by experimental methods becomes difficult. Therefore, it is worthwhile to carrying out a theoretical research.In this paper, a DFT study on the mechanism of dearomatization reaction between chloromethylnaphthalene and 1-methylpiperazine was performed. We designed all possible reaction paths, optimized the structures of all reactants, intermediates, transition states and products, calculated the potential energy surface. Furthermore, we calculated vibration frequencies of each structure to confirm whether the structures are minima with no imaginary frequency or transition states with only one imaginary frequency. Intrinsic reaction coordinate (IRC) calculations were also performed to confirm that the transition states indeed connect two corresponding minima. Our results show that the whole process include three steps: oxidative addition, transmetallation and reductive elimination. Two reaction paths were calculated in oxidative addition process, the free energy barrier are 6.47 Kcal/mol and 15.94 Kcal/mol respectively. By comparing the free energy barrier of oxidative addition, transmetallation and reductive elimination process, we conclude that the free energy barrier of reductive elimination is the highest, so it is the rate-controlling step of the reaction. Finally, solvent effects of Tetrahydrofuran and 1,2-Dimethoxyethane were calculated by using solvation model SMD. The results showed that the free energy of all reactant, catalyst, intermediate, transition states and product were reduced in both solvents, the stability of every structures were enhanced. In addition, the free energy of transition states is lower in DME solvent, so the yields should be higher theoretically.