The Mechanism Of Transition Metal Oxidation State Transformation In Coupling Reaction

Transition metal catalyzed coupling reaction is one of the most efficient synthesis strategies to construct new carbon-carbon bonds or carbon-hetero atom bonds in organic reactions.Thanks to the research and exploration during the past several decades,this strategy has been widely used in the synthesis of important compounds involved in pharmacy,agrochemistry,materials and other fields.Due to its great efficiency,it has become a hot spot of research in recent years.With the design of new transition metal catalysts,various reaction substrates,different ligands and additives,the types of transition metal catalyzed coupling reactions have become more abundant.Meanwhile,the corresponding theoretical research becomes more complicated and significant.Transition metals,which bridge the transformation from inert substrates to coupling products,are usually accompanied by the change of oxidation state.So the problems about clarifying the interaction mode between transition metal and reaction substrate,understanding transition metal oxidation state transformation mode,explaining the detailed process of chemical bonds generation and conversion,elucidating the coupling reaction mechanism,and revealing the general rules of these reactions,are the top priority for the research about new types of coupling reactions.Due to the advantages of theoretical computational chemistry,the oxidation state transformation mechanisms of the active transition metal intermediates in a series of coupling reactions were studied.Among these reaction processes,we focus on the following aspects:electron transfer modes in the activation of substrates and transition metal centers;the ability of transition metal to gain or lose electrons;the transformation of formed C-M bonds;and the change of oxidation state of transition metal center in the catalytic cycle.Our aim is to provide theoretical support for experimental design of coupling reaction,and to provide ideas for broadening the range of coupling reactions.It will provide a guidance for the future development of coupling reactions.The research contents are mainly divided into the following two parts:1.Theoretical calculation was used to study the mechanism of cycloketene activation catalyzed by transition metal with double electron transfer property.We found when the inert molecules are multifunctional cyclic,such as cycloketene,the size of the ring will induce transition metals with different oxidation states to participate in the reaction.At the same time,the activation modes in the changing of metal center's oxidation state are also different.This determines the diversity of molecules constructed after the catalytic process.1.1 Density functional theory(DFT)was used to investigate the mechanism of a series of rhodium-catalyzed cyclopropenone activation processes.The calculated results showed that the general catalytic cycle of this kind of reaction was as follows:alkyl-Rh(III)or aryl-Rh(III)intermediates were obtained by Rh(III)cation mediated C-H bond activation.Then cyclorhoda(V)butanone intermediate with a high oxidation state was formed with double electron transfer oxidation activation mode.Subsequent reductive elimination afforded vinyl Rh(III)complex.After protonation,the coupling product was generated.Our theoretical calculation excluded the carbonyl insertion activation mode for cyclopropenone with constant oxidation state.,and also confirmed that the change of oxidation state in these reactions is corresponding to the III-V-III catalytic cycle.GRI calculation and NCI analysis of different reactivity and regioselectivity also confirmed the rationality of the oxidation state change model.1.2 The mechanism and the origin of enantioselectivity in palladium catalyzed divergent higher-order cycloadditions of tropone activation were revealed by DFT calculation.Computed results showed that in the construction of these bicyclic compounds,the changing of oxidation state of the palladium center in the catalytic process follows the 0-II-0 cycle.Low oxidation state palladium(0)was activated by?-methylidene-?-valerolactones with double electron transfer type substitution oxidation to form zwitterionic allyl-Pd(II)intermediate.The formation of enantiomers by the nucleophilic attack of allyl-Pd(II)onto the?-position of Si or Re face in tropone was the rate-determing step.The followed intramolecular nucleophilic addition of the enantiomers selectively gave the cycloaddition products and simultaneously regenerated the active palladium(0)catalyst via reductive elimination.The selective formation of bicyclic compounds was related to the intramolecular hydrogen bonds,the multiple reaction sites of tropone and the thermodynamic stability of cyclic products.2.Theoretical calculation was used to study the mechanism of alkyl halides activation and the construction of C(sp~2/sp~3)-C(sp~3)bond catalyzed by nickel,which has a single electron transfer property We also found that specific electrophilic reagents can be selectively activated by adjusting the reactivity of nickel species with different oxidation states,and then alkylation can be achieved with high regioselectivity.2.1 The mechanism and regioselectivity of nickel catalyzed migratory Suzuki-Miyaura coupling reaction between alkyl halides and aryl boronic acids were researched by DFT calculation.The calculation results showed that in the presence of BC bidentate nitrogen ligand,the oxidation state of nickel center in the formation of migratory diaryl alkane derivatives undergoes the 0-I-II-0 cycle.The detailed mechanism included the activation of alkyl halides to produce bromonickel(I)by the inner sphere single electron mode of nickel(0)catalyst,the genearion of alkyl-nickel(II)through single-electron oxidation of alkyl radical,the formation of benzyl nickel(II)intermediate via chain-walking process,the stepwise transmetallation of nickel(II)in oxidation state,and reductive elimination.The thermodynamic stability of benzyl nickel species was the driving force of nickel chain-walking.2.2 DFT calculation was used to study the mechanism of nickel catalyzed highly regioselective alkene dialkylation.The complicated oxidation state changing process of nickel center was 0-I-II-I-II-III-I-0 in the catalytic cycle.The first alkylation was realized through selective activation of NHPI ester by active nickel(0)species,directly single electron oxidation between alkyl radical and nickel(I)center,and intramolecular olefin insertion in the alkyl-Ni(II)complex.With the reduction of Mn,the generated alkyl-Ni(I)selectively activates iodoalkane and then undergoes single-electron oxidation and reductive elimination to achieve the second alkylation.Theoretically,the observed selectivity in the dialkylation of alkene is mainly attributed to two aspects.One is the compatibility of strong nucleophilic nickel(0)species and the strong electrophilic NHPI ester.Another is the weak distortion between the alkyl-Ni(I)compounds and the less sterically hindered iodoalkane.