Theoretical Studies Of Molecular Mechanism On Some Improtant C-X(X=H,C,N) Bond Activation/Coupling Reactions Catalyzed By Transition Metal Complexes

As a new emerging interdiscipline,organometallic chemistry has always been one of the most active research topic in the field of synthetic chemistry.Transition metal complexes have a wide range of applications in the fields of biomass degradation,organic synthesis,pharmaceutical engineering,and green chemistry due to their anti-toxicity,good thermal stability,long service life,high selective oxidation and low price.However,some reaction phenomena and results in these fields cannot be explained reasonably,and the mechanisms of some reactions are still unclear,which limit the development of organometallic chemistry and new catalysts to a certain extent.Exploring and revealing the reaction mechanism at the molecular level,explaining the experimental phenomenon,and deeply understanding the nature of the reaction through theoretical and computational chemistry research can lay a certain theoretical foundation for the development of organometallic chemistry.In this dissertation,we select C-X(X=H,C,N)bond activation/coupling reactions catalyzed by transition metal complexes such as nickel,ruthenium,palladium and copper as the research objects based on the background of relevant experimental literature.DFT calculations have clarified some experimental microscopic mechanisms,discussed the thermodynamic and kinetic properties of the reaction,explained the chemoselectivity,regioselectivity,and enantioselectivity of the reaction,analyzed the effect of ligands and additives on the reaction performance,obtained some innovative research results,and provided some theoretical guidance for the design of efficient catalysts.The main contributions and key innovations of this dissertation are summarized as follows:1.This work presents a DFT-based computational study on the regio-and enantioselective C-H functionalization of pyridines with alkenes at the relatively unreactive C4-position using Ni(0)/N-heterocyclic carbene(NHC)catalysis under the assistance of an aluminum-based Lewis acid additive MAD.The calculations clarified the reaction mechanism,explained the origin of the regio-and enantioselectivity and the effects of ligand and additive.DFT calculations indicate that the selective functionalization involves a three-step mechanism(coordination,HMAOM,and reductive elimination),instead of the four-step mechanism(coordination,C-H oxidative addition,alkene insertion,and reductive elimination)proposed by the experiment author,where a unique H-migration assisted oxidation metalation(HMAOM)step is identified as the rate-and enantioselectivity-determining step.The newly proposed mechanism can well rationalize the experimental observation that the preferred product is the endo-type(vs exo-type),R-configuration(vs S-configuration)product at the C4(vs C2)position,and also unveil the reasons that the NHC ligand and the MAD additive can facilitate the reaction.With the unique mechanism,the enantioselectivity of the reaction towards the desired product is attributed to the smaller H…H repulsion effect in the R-configuration transition state than that in the S-configuration.The favorable endo-type product over the exo-type product is due to the stronger nucleophilicity of the terminal alkene carbon atom than the internal alkene carbon atom.The preferred regioselectivity at the pyridine C4 position stems from both the smaller steric effect and the stronger electronic effect at this position in the HMAOM process than at the C2 position.The NHC ligand facilitates the reaction via enhancing the Ni(0)catalyst activity,while the MAD additive assists the reaction via activating the substrate,and both of them play substantial roles for the regio-and enantioselective C-H cyclization of pyridines with alkenes.This work has been published on Chemistry-A European Journal(2020,26,5459-5468).2.Density functional theory calculations have been carried out to elucidate the mechanism,and clarify enantio-,regio-,and chemoselectivities,and the role of NHC ligand in the Ni/NHC-catalyzed alkylation of fluoroarenes with alkenes.The reaction is found to follow a concerted ligand-ligand hydrogen transfer(LLHT)mechanism instead of the stepwise oxidative addition/alkene insertion mechanism.The high R-enantioselectivity originates from the stronger agostic interaction in the R-configuration than that in the S-type enantiomer,the exclusive endo-regioselectivity is controlled by the stronger electrostatic force of the Ni(0)catalyst with the terminal carbon atom than the internal carbon atom in the alkene,and the excellent chemoselectivity of C-H activation over C-F activation attributed to the more favorable concerted ligand-ligand hydrogen transfer(LLHT)mechanism of C-H activation than the stepwise mechanism of the C-F activation.The enhanced reactivity by NHC ligand is attributed to the raise of the catalyst HOMO level via the highly electron-donating effect of the NHC ligand.This work has been published on Organic Chemistry Frontiers(2021,8,1520-1530.).3.This work presents a DFT-based theoretical study on the cross-coupling reaction of alkyl carboxylic acids and nitrogen nucleophiles via dual copper and photoredox catalysis.It was found that chlorinated indazole nucleophile(R1)prefers the C-N coupling at the indazole secondary amine nitrogen to at the tertiary amine nitrogen,while in the situation of heterocycle(R2),the preferred coupling occurs at the indazole nitrogen rather than at the primary amide nitrogen.The calculations showed the mechanistic details of three subprocesses proposed in the experimental study,including production of alkyl radicals,iridium(?)photoredox cycle,and copper(?)thermalredox cycle.It is found that alkyl radicals can be easily produced from primary,secondary,or tertiary carboxylic acids through iodonium activation.The energetically most favorable cross-coupling pathway involves coordination,deprotonation,single electron transfer(SET),radical addition,and reductive elimination.For the chlorinated indazole nucleophile(R1),the preferred C-N coupling product from 1H-tautomer are attributed to its higher stability relative to 2H-tautomer and the high barrier involved in the tautomerism from 1H-tautomer to 2H-tautomer.While in the case of heterocycle(R2),the C-N cross coupling preferentially occurs at the indazole nitrogen rather than at the primary amide nitrogen,which is confirmed to be due to the stronger acidity of the indazole N-H unit in comparison with the primary amide N-H unit in the indazole side chain.The theoretical results provide help for understanding the molecular mechanism and regioselectivity of the title reaction.This work has been published on Inorganic Chemistry.(2019,58,12669-12677).4.DFT calculations were performed to investigate the coupling reaction of vinyl carboxylates with arylboronic acids catalyzed by Pd(II).Pd-catalyzed cross-coupling reactions generally occur by the traditional Pd(0)/Pd(II)mechanism.A distinct Pd(?)-only mechanism has been suggested recently for the base-free cross-coupling of vinyl carboxylates with arylboronic acids at ambient conditions that is enabled by Pd(OAc)2 along with a phosphine ligand.This computational study elucidates the new Pd(?)-only mechanism,explained the regioselectivity of the reaction,and clarified the molecular mechanism of the reaction induced by the ligand..Transmetalation involving the arylboronic acid delivers the aryl group to the Pd(?)intermediate,which allows the carbopalladation of the vinyl acetate via C=C insertion into the Pd-aryl bond.The resulting ?-carbon-bound Pd(II)keto complex undergoes 1,3-palladatropic shift via keto-enol tautomerism to achieve the epimerization of the ?-carbon,in which process transient water molecules play the vital role of proton shuttles.Consequently,the Pd(?)center and the ?-acetate group are properly oriented for the ?-elimination to furnish the coupling product and regenerate the active species.The rate-and regioselectivity-determining carbopalladation via C=C insertion is facilitated by the phosphine ligand's aryl substituent inducing noncovalent ? stacking interactions with the Pd(?)-bound aryl group.This reveals the origin of the ligand-controlled catalyst activity.The insights gained by this study can help utilize the Pd(?)-only mechanism for a wider range of challenging cross-coupling reactions.This work has submitted to ACS Catslysis and are currently being revised.5.Focusing on the degradation mechanism of lignin model compound catalyzed by[Ru(Cl)(H)(PPh3)3].The experiment show that the degradation of lignin model compounds can effectively catalyzed by the ruthenium complex[Ru(Cl)(H)(PPh3)3],that is,the cleavage of the C?-C? bond in 1,3-dilignol,and the reaction can occur without the addition of oxidants.With the aid of DFT calculations,we have performed the proposed mechanism divides the reaction into four stages:coordination,dehydrogenation,retro-aldol-type C-C bond cleavage,and product and pre-product release with catalyst regeneration.The dehydrogenation process was identified as the bottleneck of the catalytic cycle and the estimated high barrier(29.8 kcal/mol)qualitatively rationalizes the experimental observation that the reactions were carried out under elevated temperature(160 ?).Calculations show that the ?-hydroxyl and ?-hydroxyl groups as well as the y-H in the lignin model compound play substantial roles and their simultaneous presence is necessary for cleavage of the C?-C? bond.This rationalizes the experimental finding that[Ru(Cl)(H)(PPh3)3]/triphos complexes were inactive for cleavage of the C?-C?bond cleavage of lignin model compound with any absence of the ?-hydroxyl group,y-hydroxyl group,or C?-H unit.This work has been published on Molecular Catalysis(2019,471,77-84).