Mechanistic Studies On Cycloaddition Reaction And C-H Insertion Involving Metal Carbenes

Divergent synthesis catalyzed by transition metals is one of the important scientific problems in the field of organic synthesis.Different from traditional convergent synthesis,divergent synthesis enables the same reactants to synthesize products with different structures under similar reaction conditions.It can efficiently construct a molecular library with high structural diversity,which is of great significance to modern organic synthesis.In the reactions involving metal carbenes,the divergence in the product formation can be achieved by judicious choice of metal catalysts or by changing the electronic and steric properties of the coordinating ligands.Despite advances in the field of divergent synthesis in recent years,developing new strategies to control the chemo-and regioselectivity and diastereoselectivity during the transformations is still highly desirable.In this dissertation,the mechanism of highly selective divergent cycloaddition of enol diazo compounds andα-diazo carbonyl compounds catalyzed by copper(Ⅰ)and rhodium(Ⅱ)was studied by density functional theory(DFT)calculations.Under the catalysis of copper(Ⅰ),the mechanism of[3+3]-cycloaddition reaction mainly includes the formation of carbonyl ylide,[3+2]-cycloaddition,nitrogen dissociation,C-C bond cleavage and carbocyclization.For rhodium(Ⅱ)catalyst,the[3+2]-cycloaddition reactions between rhodium-enol carbene and the in situ generated ketene-N,O-acetal take place.The catalytic mechanism includes the formation of ylide,proton transfer,keto-enol tautomerization,carbene formation and C-C bond formation.We used deformation-interaction(DI)analysis,natural population analysis(NPA)and non-covalent interaction analysis to further explore the origin of chemoselectivity and regioselectivity,and investigate the effects of electronic and steric effects on the activation energy.For the formation process of ketene-N,O-acetal intermediate,the calculation results show that the proton transfer step is first transferred to carbonyl oxygen atom with the assistance of water,followed by the hydrogen transfer through ketene-enol tautomerization.Secondly,the mechanism and the origin of regioselectivity of Au(Ⅰ)-catalyzed C-H bond functionalization of naphthol withα-aryl-diazoate were investigated.With Johnphos as the ligand,the para-selective C-H functionalized products were generated.When the ligand becomes IPr,the ortho-substituted products can be obtained.The catalytic cycle mainly includes:(i)the formation of gold-carbene from diazo compounds and active catalysts;(ii)C(sp~2)-C(sp~2)bond coupling between carbene carbon atoms and aromatic carbon atoms of naphthol;(iii)water-assisted[1,3]-hydrogen transfer;(iv)catalyst regeneration.During the process of proton transfer,water in the solvent was found to play a crucial role in remote proton transfer.It proceeds via water-assisted[1,3]-hydrogen transfer rather than the direct[1,2]-hydrogen transfer mechanism.In addition to the carbene mechanism,the Lewis acid mechanism was also investigated.The catalytic cycle includes:(i)the active catalyst acts as Lewis acid to coordinate with the nitrogen atoms of diazo compounds to form carbocation intermediates;(ii)electrophilic addition of aromatic carbon atom of naphthol with carbocation;(iii)aromatization,denitrification and protonation reactions;(iv)regeneration of catalysts.The calculations reveal that the Lewis acid path can be excluded since it is kinetically unfavorable.The research content in this dissertation reveals the important influence of metal and ligand on the reactivity and selectivity of carbenes.The relevant mechanistic insights will help to further develop the discrimination strategy of two different diazo compounds.The controlling mechanism of electronic and steric effects on regioselectivity revealed by current theoretical studies has certain guiding significance for the further development of transition metal-catalyzed regiodivergent cycloaddition and C-H insertion reactions.