Synthesis Of Nitrogen-containing Heterocyclic Compounds By Functionalization Of N-ortho-C(sp~3)-H Bond

N-heterocyclic compounds are widely found in natural products,pesticides and pharmaceuticals.Pyrazoles and imidazolo[2,1-a]isoquinolines are two important N-heterocyclic compounds,which are the core blocks in many organic molecules,and play an important role in the fields of medicine,pesticides,functional materials and organic synthesis.Therefore,various efficient new methods for the synthesis of pyrazoles and imidazolo[2,1-a]isoquinolines have been explored by chemists.In recent years,the functionalization of N-ortho-C（sp³）-H bond is considered to be a reliable method for the synthesis of complex nitrogen-containing heterocyclic compounds with high step-and atom-economy.The functionalization of N-ortho-C（sp³）-H bond involves three different intermediates including imine ion intermediates,α-aminoalkyl radical intermediates and methimine ylide intermediates.The main research work of this thesis focused on the functionalization of N-ortho-C（sp³）-H bond to synthesize substituted pyrazole compounds and imidazolo[2,1-a]isoquinoline compounds by producing imine ion intermediates and methimine ylide intermediates.At the same time,the substrate adaptability,application,and reaction mechanism of the reactions were also discussed.（1）A new method for the synthesis of substituted pyrazoles from N,N-disubstituted hydrazines and alkynyl esters have been developed by[3+2]cycloaddition using Cu₂O as promoter,Cs₂CO₃ as base,and oxygen in air as oxidant.The functionalization of the N-ortho-C（sp³）-H bond was achieved through the generation of imine ion intermediates during the reaction process.This work involved a direct functionalization of C（sp³）-H and the formation of new C-C/C-N bonds.In this strategy,inexpensive and easily available Cu₂O served as the promoter and air acted as the green oxidant.The reaction exhibited the advantages of high atom-and step-economy,high regioselectivity,and easy operation.The structural modification and derivation of the target compounds were investigated,which showed the practical application value of the reaction in drug synthesis.（2）Imidazolo[2,1-a]isoquinoline blocks have good biological activity,we discovered a novel approach for the synthesis of imidazolo[2,1-a]isoquinolines from isoquinolinium salts and amidine hydrochlorides through[3+2]cyclization under 10 W blue light irradiation using Ru（bpy）₃Cl₂ as photocatalyst,DBU and cesium carbonate as bases.The reaction involved photoredox and oxidative aromatization process.Meanwhile,this work featured the direct functionalization of N-ortho-C（sp³）-H and the formation of new C-C/C-N bonds.The possible mechanism involved the formation of methimine ylide intermediates from isoquinolinium salts.This method had the advantages of mild reaction conditions and simple operation,and easily modification providing a new strategy for the synthesis of drugs with imidazolo[2,1-a]isoquinoline blocks.