Mechanistic Study On Transition-Metal-Catalyzed C-O Bond Activation Reactions

Oxygen-containing functional groups(such as hydroxyl,carbonyl,carboxyl,etc.)are widely found in natural products and biomass feedstocks,thus their transformation via C-O or C=O bond activation is highly desired for natural product modification and the green synthesis of high value-added chemicals.In recent years,great achievements have been made in transition-metal-catalyzed carbon-oxygen bond activation/functionalization reactions and a large variety of compounds have been prepared(?)protocols.However,the princip(?)laws behind the experimental observations are still unknown for a considerable part,which hinders the further optimization and development of the reactions.With the great progress in computer technology and the continuous improvement of quantum chemical methods,the theoretical calculation has become a powerful tool to elucidate the preferred mechanism and the factors controlling the efficiency of the reaction.Herein,we performed systematically studies on several transition-metal-catalyzed carbon-oxygen bond activation reactions by means of density functional theory(DFT)calculation.The first chapter briefly introduces the representative work of transition-metal catalyzed carbon-oxygen bond activation reactions in recent years.It is divided into three parts according to the type of carbon-oxygen bond:C(sp3)-O bond activation,C(sp2)-O bond activation,and the C=O bond activation.The investigations of the reaction mechanism are particularly highlighted,especially the theoretical studies in this field.In the second chapter,the mechanism of the nickel-catalyzed silylation of aryl methyl ethers has been systematically investigated using DFT methods.This theoretical study supports a catalytic cycle involving the formation of a nickel-silyl complex,C-O bond cleavage,C-Si reductive elimination,the addition of methoxide to boron,and final regeneration of the catalyst.We found that the C-O bond cleavage is the rate-determining step,and the classical oxidative addition pathway with a three-centered transition state is most favored compared to other activations modes.The silyl anion generated in situ works as a ligand to the nickel center and promotes this process together with the potassium ion derived from the base.The resting state is identified as the adduct of KOtBu and silyl boronate involved in the formation of the nickel-silyl complex.In this case,the resting state is destabilized due to steric repulsion introduced by tert-butoxide.As a result,the overall barrier of the reaction is reduced relative to that with bases comprising other anions,which is consistent with the experimental results.In the third chapter,the mechanism of the ruthenium-catalyzed site-selective hydrogen transfer reaction was investigated.It was found that this reaction proceeds via an inner-sphere pathway,which involves the formation of the Ru-alkoxide complex,the-H elimination(which generates a Ru-H complex and ketone),the hydride transfer from the Ru-H complex to acetone,and the protonation of isopropoxide.It was found that both the ?-H elimination and the protonation of isopropoxide can be the rate-determining steps,depending on the properties of the substrate.Large steric hindrance and low electron density around the hydroxyl group would increase the barrier of ?-H elimination,while an adjacent coordinating group has the opposite effect.Meanwhile,the relative stability of the oxidation product also weighs on the overall barrier.All the above factors contribute to the selectivity of the hydroxyls in different environments.In addition,the reactive site in a polyhydroxy complex is well predicted,demonstrating the potential of theoretical conclusions in practical applications.In the fourth chapter,we conducted a mechanistic study on the carboxylation of aryl halides with CO2 promoted by the combined use of palladium and photoredox catalysts.We found that after the oxidative addition between the aryl halide and palladium catalyst,the Ar-Pd(II)-X intermediate is generated,which would be reduced to a strongly nucleophilic Ar-Pd(0)anion with the assistance of the photocatalyst and amine.Subsequently an ?1-C type Pd(0)-CO2 complex forms?then the aryl group attack the activated CO2 feasibly,leading to the carboxylation product.Meanwhile,the electron transfer and proton transfer between the Ar-Pd(I)intermediate and the amine radical cation generated in situ does account for the hydrodehalogenated product.The addition of external base can reduce the concentration of the amine radical cation thus suppress this process effectively.