Density Functional Theory Study Of C-H Bond Activation And Selectivity Catalyzed By Transition Metal Palladium

In recent years,the C-H bond activation catalyzed by transition metals has developed successfully and has been widely used in the synthesis of various organic compounds,playing an important role in the field of organometallic chemistry.One of the tremendous challenges to promote the C-H bond activation is to distinguish multiple C-H bonds with similar electronic properties and bond strengths during the reaction process.This problem often leads to poor reaction selectivity,which is difficult to obtain the target product.Especially for some chiral organic compounds with medicinal value,the selectivity of them is required to be much higher.In order to solve this problem,organic synthesizers have realized the control of selectivity by adding various directing groups and ligands to the reaction system,which improved the selectivity of the C-H bond activation to some extent.However,for some more complex reaction,the observations in experiments sometimes fail to provide a reasonable explanation for the experimental phenomena.In addition,some intermediates cannot be captured in time through experimental methods due to their extremely short existence time.Computational chemistry has made up for the above shortcomings.Calculations of the elementary reaction steps can effectively derive the specific mechanism of the reaction.In parallel,the analysis of steric repulsion,charge effect,orbital interaction,etc.,is useful to clarify the reaction activity and selectivity.Therefore,theoretical understanding of the mechanism factors determining experimental observations is of great significance,especially for the selection of experimental conditions,substrate design,and ligand selection for transition metal catalyzed organic synthesis reactions of C-H bonds.On basis of the reported experiments,in this dissertation,density functional theory（DFT）,energy decomposition analysis（EDA）,and natural orbital analysis（NBO）were employed to systematically study the selectivity of the transition metal palladium catalyzed inert C-H bond activation process,providing some theoretical guidance for the design of catalytic system of related reactions.The main research contents and conclusions are summarized as follows:（1）The mechanism of the selective arylation of the C-H bond catalyzed by Pd catalyst,together with a 2-pyridone ligand and a pyruvic acid-derived directing group was systematically studied.The functionalization of the C-H bond may take place via a dimeric palladium catalyst[Pd₂（OAc）₄]or a monomeric palladium catalyst[Pd（OAc）₂].The calculated results show that the former is more consistent with the experimental results and EDA calculations confirm that the reaction selectivity is mainly determined by electrostatic interaction and orbital interaction.In addition,in the presence of the phosphine ligand,the intermediate obtained by the reaction via the dimeric palladium mechanism can transfer to the monomeric palladium intermediate through a ring contraction process.The reaction procedure from aryl iodide to arylated alcohol is comprised by O-H bond activation,C-H bond cleavage,aryl-I bond oxidative addition,ion exchange,C-C bond reductive elimination and deprotonation to yield the final product and regenerate the catalyst.In the titled reaction mechanism,the cleavage of C-H bond is proved to be both the rate-limiting step and selectivity-determining step.And also,the above conclusions can be reasonably applied to the titled reaction with 2,3,5,6-tetrafluoro-4-CF₃-phenyl amine as the directing group,further confirming the rationality of the dimeric palladium mechanism.（2）The mechanism,origin of stereoselectivity,and ligand-dependent reactivity of Pd（II）-catalyzed methylene C（sp³）-H bond alkenylation-Aza-Wacker cyclization to form（E）-β-stereo-genicγ-lactam have been comprehensively studied.The calculated results reveal that the methylene C-H activation assisted by K₂CO₃ via the concerted metalation-deprotonation mechanism is found to be the most preferred pathway,where the enantioselectivity is distinguished by the orientation of the methyl group of the substrate relative to the chiral ligand.However,the stereochemistry of the olefin moiety in the generated product is mainly determined by the oxidative addition step,where the coulombic interaction and dispersion effect differentiate the energy difference of diastereomeric transition states.In terms of the agostic interaction nature of“three-center two-electron”transition states,the discrepancy of reactivities caused by different Pd catalysts is attributed to the electron induction effect of substituents on the chiral ligands.In other words,the use of an electron-withdrawing group（e.g.,-CN）in place of an electron-donating group（e.g.,-OMe）enhances the oxidation state of the Pd atom and lowers vacant d orbitals of the palladium atom of the catalyst and in turn facilitates a larger amount ofσ-electronic-charge injection into an empty 3d shell of the palladium center.Thus,the higher catalytic activity of the Pd catalyst with ligands substituted by an electron-withdrawing group（such as cyano group）is anticipated.