Theoretical Study On Palladium-Catalyzed Multicomponent Cycloadditions Of Halobenzene

Palladium-catalyzed multicomponent cycloaddition reaction is one of the most important methods for quick construction of carbon rings by forming carbon-carbon bonds.In this thesis,palladium-catalyzed[4+2]cycloaddition reaction of o-vinyl bromobenzene with bromobenzene,as well as palladium-catalyzed[2+2+1]cycloaddition reaction of 1,2-dihaloarene,alkyne with 2-naphthol,have been explored in detail by employing density functional theory（DFT）.After obtaining the potential energy profiles of aforementioned reactions,probable mechanisms of these two reactions were further analyzed,to help people understand the reaction mechanism and selectivity regulation mechanism of these reactions deeply,at a microscopic level,and provide theoretical reference for the improvement of experimental conditions for similar reactions.The thesis contains five chapters.In Chapter 1,research progress of several types of palladium-catalyzed cycloaddition reactions were reviewed briefly,with the significance of topics discussed in this thesis summarized in the end.In Chapter 2,computational background knowledge and common theoretical methods employed in this thesis were introduced in brief.In Chapters 3 and 4,detailed computational results about palladium-catalyzed[4+2]and[2+2+1]cycloaddition reactions were introduced,respectively.Finally,a conclusion for the whole thesis was made in Chapter 5.Main contents and conclusions of Chapters 3 and 4 are as follows:1.Based on computations about the palladium-catalyzed[4+2]cycloaddition reaction of o-vinyl bromobenzene with bromobenzene,possible reaction mechanism of this reaction was explored.The reaction mainly undergoes oxidative addition of C-Br bond,ligand exchange,K₂CO₃-assisted vinyl-C（sp~2）-H activation,transmetallation,C-C coupling,K₂CO₃-assisted aryl-C（sp~2）-H activation and C-C reductive elimination processes,with the desired[4+2]cycloaddition product phenanthrene（P1a）obtained in the end.The aryl-C（sp~2）-H activation step is found out to be the rate-determining step（RDS）of the whole reaction,spanning a Gibbs free energy barrier of 30.5 kcal·mol^-1on the optimal reaction pathway,whose result is in good agreement with corresponding experimental results:a 90%yield of P1a at130°C after 5.0 h reaction.The rate-determining step predicted by computation is also consistent with corresponding kinetic isotope effect experimental results.By comparing with CAM-B3LYP,LC-ωPBE,M06-2X,B3LYP-D3 andωB97XD methods,the Gibbs free energy barrier corresponding to RDS obtained by using B3LYP method(30.5 kcal·mol^-1)is found out to be the lowest and can be overcome easily under corresponding experimental temperature（130℃）,thus gives out a prediction of half-life time（1.1 h）which fits best with corresponding experimental reaction time（5.0 h）.Based on computational study on the cases with and without K₂CO₃base additive,it is found that the participation of K₂CO₃makes the Gibbs free energy barriers of corresponding vinyl-C（sp~2）-H and aryl-C（sp~2）-H activation steps lower than that without K₂CO₃by 28.5 and 20.5 kcal·mol^-1respectively.These computational results explain well the crucial role of base additives in this reaction.Based on computation of possible formation mechanism of by-products P2 and P3,it is found that the rate-determining step’s Gibbs free energy barriers corresponding to the formation of by-products P2 and P3 are 2.5 and 6.6 kcal·mol^-1higher than that of main product P1a,which explains well the by-products P2 and P3’s disappearance in experiments.Geometrical results of the RDSs’transition states corresponding to the main and by-products’formation paths are in good agreement with corresponding free energy results.In addition,computational results about different substituents in substrates show that the Gibbs free energy barrier’s increase of reaction b relative to Path a-I in reaction a is mainly caused by electronic effect,while the increase of Gibbs free energy barrier of reaction c relative to Path a-I in reaction a is caused by both electronic effect and steric effect.Finally,computational results about the solvent effect and ligand effect also give out good agreement with corresponding experimental data.2.Based on experimental results about the palladium-catalyzed[2+2+1]cycloaddition reaction of 1,2-dihaloarene,alkyne with 2-naphthol,possible reaction mechanism of this reaction was speculated and verified by theoretical computations.Computational results show that the reaction mainly undergoes oxidative addition of C-I bond,alkyne insertion,ligand exchange,K₂PO₄^-assisted metallation-deprotonation,C（sp~2）-H activation,H-migration,C-C coupling,oxidative addition of C-Br bond,O-H activation processes,with the desired spiro products obtained through reductive elimination in the end.The reductive elimination step is found out to be the rate-determining step of the whole reaction,features a Gibbs free energy barrier of 31.7 kcal·mol^-1,which is in good agreement with corresponding experimental results:a 90%yield of Pa1 at 130℃after 16 h reaction.By comparing with M06L and B3LYP methods,the Gibbs free energy barrier corresponding to rate-determining step obtained by using M06-2X method(31.7 kcal·mol^-1)is found to be the lowest and can be overcome easily under corresponding experimental temperature（130℃）,thus gives out prediction of half-life time（3.5 h）which fits best with corresponding experimental reaction time（16 h）.When employing K₃PO₄base additive,the relative Gibbs free energy of each stationary point,as well as the total Gibbs free energy barrier corresponding to the stage reaction from INT2a-1 to INT8a-1 are lower than that of the Na₃PO₄ones.These computational results reasonably explain the experimental fact that the reaction yield employing K₃PO₄base additive is significantly higher than that of the Na₃PO₄case.In addition,computational results about the regioselectivity also give out good agreement with corresponding experimental data.