Theoretical Studies On The Selectivity Of Pd-Catalyzed C-H Activation And C-C Coupling

The construction of new C-C functional bond through C-H activation catalyzed by transition metal complexes has been attracted wide attention in recent decades.Among them,palladium-catalyzed C-H activation and C-C coupling reactions are the most widely used reactions.A variety of new functional organic molecules can be synthesized by appropriately selecting ligands and catalytic systems.At present,despite significant progress,achieving precisely selective regulation still faces many new challenges.For example,the control problems of chemoselectivity,regioselectivity and enantioselectivity are still important scientific problems that theoretical and experimental workers need to explore and strive to solve.With the development of computational technology and the increased amount of reaction data and computational resources,the prediction of chemical reactions by theoretical calculation has become an important research direction and discipline field.Theoretical and computational chemistry has made great progress in exploring the microscopic mechanisms of chemical reactions,constructing microstructure of molecules and the relationship between macroscopic thermodynamics and kinetics,and elucidating the origin of the selectivity of chemical reaction.In this dissertation,density functional theory(DFT)calculation was used to study the detailed mechanisms and selectivity(chemoselectivity,regioselectivity and enantioselectivity)of C-H activation and C-C coupling reactions of palladium-catalyzed unsaturated hydrocarbons and aromatics.The effects of substrate,ligand and additives on chemoselectivity,enantioselectivity and regioselectivity were investigated.The study revealed the role of each component in the multi-component reaction,especially the role of norbornene and ligand in regulating regioselectivity and enantioselectivity.The main contents and innovative achievements are as follows:(1)The stereospecificity and chemoselectivity of Pd-catalyzed α,α-disubstituted alkenyl hydrazones to synthesize 1,4-dienes in the Z configuration and vinylcyclopropane was investigated.The mechanism details of the reaction and the effect of four α,α-disubstituted alkenyl hydrazones on the reactivity was explored.The overall catalytic cycle includes oxidative addition,dediazonation,migratory insertion,syn-carbopalladation,followed by syn-β-C elimination and β-H’ elimination to produced skipped diene or direct β-H elimination to produced vinylcyclopropane.The oxidative addition step is the rate-determining step of the full catalytic cycle.Current theoretical calculations reveal that the syn-β-C elimination plays an important role in determining stereospecificity and chemoselectivity.In the process of reaction,C-C bond rotation and subsequent syn-β-C elimination step control the stereospecificity of the reaction by changing the olefin stereostructure from E to Z configuration.The syn-β-C elimination step increases significantly in energy with change of α-substituted groups from methyl,cyclopropyl to more flexible and sterically hindered ethyl and N-tosylpiperidine until it is higher than that of competitive β-H elimination,resulting in the selective conversion of skipped diene to favor cyclopropanes.(2)A novel mechanism of the arylation of arenes by means of norbornene relay palladation through meta-to para-selectivity was revealed using DFT calculations.The para-arylation product was successively via the directing group assisted meta-C-H activation,NBE insertion,and NBE assisted para-C-H arylation steps.The meta-arylation byproduct are derived from the directing group assisted para-C-H activation and NBE assisted meta-C-H arylation steps.It’s worth noting that the reaction was initiated by a [mono-N-protected amino acid ligand(MPAA)-Pd] complex to activate firstly the meta-C-H guided by the directing group.The secondary para-C-H activation is achieved through Ag(I)assisted bimetallic active species,which unravels the crucial role of the silver additive.Computational studies suggest that the directing group assisted C-H activation step is the rate determining step and also the key step of determining siteselectivity.The competitive para-C-H activation step require higher activation barriers than the meta-C-H activation,which is due to more ring strain in the cyclic nitrile-coordinated C-H activation transition states in para-position.The perfect cooperation of a remote directing template and a transient mediator NBE through the alternating association with the Pd center allows the catalytic cycle to proceed.The calculated results provide a reasonable mechanism insight for the para-C-H arylation by Pd/NBE cooperative catalysis in conjunction with a precise directing group and silver(I)additive.(3)The mechanism and origin of the NBE-controlled mono-and di-meta-C-H arylation of anisole in Pd/S,O-ligand catalysis were explored with DFT calculations.The results show that the S,O-ligand acts as a bidentate ligand to coordinate with Pd to form the active catalyst,and also acts as an internal base to extract hydrogen proton for the initial C-H activation.The NBE mediated secondary C-H activation is catalyzed by bimetallic Pd-Ag.The mono-meta-arylated product is formed from primary ortho-C-H activation and the di-meta-arylated product is generated from ortho-and para-C-H palladation of mono-arylated product.NBE mediated mono-and di-meta selectivity controlled by the meta-C-H activation,which involves two Ag-coordinated conformations with distinct steric environments.The bridgehead-modified NBE enables the Ag-NBE coordination due to the steric hindrance between the bridgehead substituent of NBE and ligands,while the unmodified NBE relies on favorable electrostatic interaction resulting in the coordination of Ag with ligand.For the Ag-NBE coordination mode,the increase of steric hindrance of bridgehead substituent leads to the geometric twisting of substrate arene skeleton overcoming “ortho constraint” ultimately resulting in the mono-meta-selectivity.Thus,using a steric hindered bridgehead modified NBE is beneficial for enhancing selectivity by controlling intramolecular interactions in meta-C-H activation step.(4)The detailed mechanism of enantioselectivity of Pd/(S)-MPAA/NBE catalyzed ferrocene aromatization was investigated through DFT theoretical calculations.The results indicate that the initial directing group assisted primary ortho-C-H activation is a rate determining step and the key step of determining enantioselectivity.This process involves the interaction between ligand and substrate and is not related to norbornene,which also explains the experimental results that chiral norbornene has useless on selectivity.The excellent enantioselectivity is due to the steric effect of catalyst,which is the distortion of the chiral ligand framework.This means that the regulation of planar chiral ferrocene selectivity can be achieved by adjusting the steric properties of chiral MPAA ligands.In addition,potassium salt acts as an internal base in the secondary meta-C-H activation process,which is beneficial for the stability of the transition state due to its favorable electrostatic interactions.The study results provide theoretical guidance for the design of catalysts in new reactions by understanding the role of ligands in selectivity.