Theoretical Studies On Nickel-catalyzed Selective Cyclization And Palladium-catalyzed Cascade Carbocyclization Reaction

Transition metal catalyzed organic synthesis has always been the focus of organic chemistry research.This kind of reaction can effectively construct common chemical bonds such as carbon-carbon bond and carbon-hybrid bond,which has the advantages of high atomic economy,low cost and environmental friendliness.It is one of the most promising ways to develop new sustainable synthesis methods.Although some progress has been made in this kind of reaction,the mechanism of the reaction is not thoroughly studied.The theoretical study of transition metal catalysis can further explore the mechanism of chemical reactions and provide theoretical support for better design of experimental reactions.Therefore,in this paper,the mechanism of selective cyclization catalyzed by Ni and cascade carbon cyclization catalyzed by Pd was studied in detail by using quantum computing method,and the selectivity and origin of the reactions were explained.The main work contents are as follows:（1）The detailed mechanism of ligand-controlled divergent synthesis via tunable cyclization in Ni-catalyzed was theoretically calculated and studied using density functional theory（DFT）.The uniform mechanism of the initial reaction is to reduce the pre-catalyst(Ni^Ⅱ)and then oxidize the resulting activated nickel to aryl bromide.Subsequently,two different mechanisms have been elucidated:the bidentate ligand facilitates the nucleophilic addition of aromatic halides,and then the product 3a is obtained by 1,4-acyl transfer and cross-coupling.The product 4a was obtained by the seven-membered cyclization and cross-coupling of the tridentate ligand.The origin of regional selectivity controlled by ligand and its related factors are discussed.For the bidentate ligand,the dominant electronic effect can explain the chemical selectivity observed in the experiment.For the tridentate ligand,the selectivity of the product can be attributed to the influence of steric effect.（2）The mechanism of high diastereoselective palladium-catalyzed cascaded carbocyclization was theoretically calculated and studied by using density functional theory（DFT）.The olefin insertion is calculated to be the rate-diastereoselectivity-determining step.The diastereoselectivity could be attributed to the existed weak interaction.The pathway leading to six-membered product,in which the CO insertion is prior to the olefin insertion,is calculated to be unfavorable,in agreement with the experimental observations.The combined electronic effect and steric effect is responsible for this observed regioselectivity.（3）The reaction mechanisms of the palladium-catalyzed oxidative cascade reaction of phenylacetylene and allenes with different assisting groups have been theoretically investigated with the aid of density functional theory calculations（DFT）.Both reactions A（Pd（OAc）₂-catalyzed cascade reactions of phenylacetylene with the allene bearing hydroxyl group）and B（Pd（OAc）₂-catalyzed cascade reactions of phenylacetylene with the allene bearing p-toluenesulfonamide）involve sp³C-H activation processes,but the specific reaction mechanism is different due to allenes bearing differentα-nucleophilic functionality in the substrate.On the basis of these mechanistic foundations,the influence of electronic effect and steric effect on chemoselectivity was illustrated.The present study provided more universal and deeper mechanistic insights into Pd-catalyzed oxidative cascade reaction of phenylacetylene and allenes with differentα-nucleophilic functionality（e.g.OH,NHR）.