Theoretical Studies On C-H Bond Activation And Functionalization Via Synergetic Photoredox/Chiral Phosphoric Acid Catalysis And Manganese Catalysis

In recent years,C-H bond activation and functionalization have become an effective strategy for the synthesis of many complex molecules.The combination of photoredox catalysis and organocatalysis has the advantages of environmental friendliness,strong redox ability,mild reaction conditions,good functional group tolerance and high selectivity.Therefore,utilizing the synergistic combination of photoredox catalysis and organocatalysis to achieve C-H bond activation and functionalization has draw great interest in organic synthesis chemists.On the other hand,3d transition metals have the advantages of abundant content in the earth,low price,and high catalytic activity.Thus,3d transition metals have become one of the choices of chemists looking for high-efficiency catalysts,and increasingly used in C-H functionalization.However,mechanisms of C-H activation and functionalization via combining photoredox catalysis and organocatalysis as well as the Mn catalysis are ambiguous.In addition,origins of enantio-and regioselectivities of these catalytic reactions are still unclear,moreover how substrate and solvent affect the selectivities observed experimentally has not been explained.These problems hinder the further development of related reactions.So,it is necessary to carry out related theoretical research by using DFT method to explain scientific problems that cannot be solved experimentally.It is expected that the calculated results can provide theoretical guidances for developing related reactions.In this thesis,we select photoredox/chiral phosphoric acid catalyzed as well as Mn catalyzed C-H activation and functionalization as the research objects.Through systematic theoretical research,mechanisms and origins of enantio-and regioselectivities of catalytic functionalization of C-H bond have been revealed,in addition influences of substrates and solvents on reaction selectivities have been elucidated.The research contents and innovation results of this thesis are summarized as follows:1.DFT study has been performed on the mechanism and origins of enantio-and regio selectivities in dual photoredox/chiral Br(?)nsted acid-catalyzed asymmetric Minisci-type addition of carbon-centered radicals to N-heteroarenes.The experemently proposed mechanism has been partially revised.Firstly,photoexcited*[IrⅢ]is reductively quenched by TRIP anion rather than the experimentally proposed neutral radical generated from the chiral Br(?)nsted acid cycle.Secondly,final product formation involves a hydrogen atom transfer(HAT)from a neutral radical intermediate to TRIP radical,instead of single electron transfer(SET)to*[IrⅢ].TRIP catalyst has been shown to play a triple role by reductively quenching*[IrⅢ]with its anion form,activating the substrate and inducing asymmetry.The calculated results rationalize the experimentally observed enantio-and regioselectivities,and reveal that enantioselectivity of the reaction originates from the hydrogen bond interaction between TRIP and the N-H group of the carbon-centered radical,and the regioselectivity arises from the electron-withdrawing inductive effect from protonated N-atom and intramolecular hydrogen bond interaction between the acetylamino group and the protonated pyridine ring.We also provide explanations for the experimentally observed dramatic decrease in enantioselectivity when changing substrate or radical precursor,and rationalize the solvent-controlled switch of regioselectivity.This work has been published on The Journal of Organic Chemistry(2020,85,7207-7217).2.The mechanism and selectivities of C(sp3)-H bond oxidative methylation catalyzed by manganese complex were studied by performing DFT calculation.The calculation results show that the formation of the active catalyst is mainly through the key intermediates of MnⅡ(CH3CN)2→MnⅡ-OH→MnⅢ-OAC→MnⅢ-OOH→MnⅢ(κ2-OOAc),of which the transformation of MnⅡ(CH3CN)2 to MnⅢ-OH is identified as rate-determining step.The geometric characteristics of the active catalyst are clarified as a cyclic structure MnⅢ(κ2-OOAc).The manganese-catalyzed methylation reaction underwent through two stages:hydroxylation process and methylation process.When the active catalyst catalyzes the hydroxylation reaction of the C(sp3)-H bond,the O-O bond is broken to obtain the MnⅣ(O·)(OAc)intermediate,which catalyzes the hydroxylation of substrates to generate the hydroxylated product via the hydrogen transfer/hydroxyl rebound mechanism.We found that two-state reactivity is shown in the formation of the active catalyst and the hydroxylation of substrates,and potential energy surface of the triplet and quintuple states are crossed.The regioselectivity is determined by the difference of π-π interaction between the phenyl group of the substrate and the arene of the catalyst of TS isomers.The methylation process contains two elementary steps,involving the departure of OH-and methylation.Firstly,OH-of the hydroxylated product is departed with the aid of the electron-deficient reagent BF3 to obtain the imine intermediate,then methylation occurs exclusively to form the methylated product,which is a thermodynamically driven process.This work is being in preparation.