Studies On The Diversity Synthesis Of Five-Membered Nitrogen-Containing Heterocycles From Nitrones And 1-Ethynylnaphthalen-2-ols

Five-membered nitrogen-containing heterocycles are extremely important nitrogen heterocyclic compounds,and also important structural units for many natural products,pharmaceuticals and bioactive compounds.It is widely used in the fields of medicine and pesticides,and played an important role in human health and agricultural production development.Nitrogen-containing ligands are also widely used in the field of organic catalysis because of its good coordination ability with metals.Meanwhile,five-membered nitrogen-containing heterocycles are also important intermediates in organic synthesis,which can be converted into indole,amino acid derivatives by simple chemical reactions.Therefore,the construction of various five-membered nitrogen-containing heterocyclic skeletons from simple and readily available starting material remains one of the main focuses of modern organic synthesis.Nitrones,as highly active 1,3-dipoles and important raw materials in organic synthesis.Cycloaddition with electrophilic reagents such as alkynes,alkenes,and allenes have not only plays important roles in the construction of nitrogen heterocyclic compounds,but also has been successfully applied into the synthesis of natural products and bioactive molecules.In recent years,α,β-unsaturated nitrones have attracted much attention from many organic synthetic chemists due to their abundant chemical conversion of unsaturated double bonds in the reaction and they can construct more and novel nitrogen heterocyclic skeletons.This paper mainly focuses on the efficient construction of various nitrogen-containing five-membered heterocyclic compounds through the cycloaddition reaction and the subsequent rearrangement strategy fromα,β-unsaturated nitrones with 1-ethynylnaphthalen-2-ols.This thesis is divided into four sections:In the first part,a method for cinchonidine-catalyzed the reaction of N-aryl-α,β-unsaturated nitrones and 1-ethynylnaphthalen-2-ols undergo[4+3]cycloaddition,[1,3]-rearrangement,ring opening,1,4-addition and intramolecular cyclizations to construct various[4.2.1]azabridged ring compounds.It is found that[4.2.1]azabridged ring compounds were prepared in good yields by using cinchonidine as catalyst in THF/CHCl₃（1:1）under 100℃.This method shows high regioselectivity and diastereoselectivity,high atomic economy,good functional group tolerance,broad substrate scope,simple operation,and easy gram scales preparation.The results showed that 1-ethynylnaphthalen-2-ols were activated by cinchonidine via hydrogen-bonding to form vinylidene o-quinone methide in situ,which underwent cycloaddition reaction with nitrones to produce seven-membered N-O vinyl intermediate.Then,it underwent a selective[1,3]-rearrangement on the N-atom rather than a[3,3]-rearrangement on the phenyl ring owing to the small steric hindrance of the styrenyl group attaching to N,O-acetal.In the second part,we investigated a copper and base co-catalyzed formal[4+1]cycloaddition of cinnamaldehyde derived N-aryl-α,β-unsaturated nitrones and 1-ethynylnaphthalen-2-ols in the presence of m-CPBA as the oxidant.The reaction underwent four steps of[4+3]cycloaddition,[1,3]-rearrangement,isomerization and oxidation to afford 2-pyrrolidones containing N-trifluoromethyl phenyl in moderate to good yields with high diastereoselectivity.Mechanistic studies revealed that m-CPBA inhibited intramolecular O-cyclization and played an important role in interrupting the intramolecular cyclization to afford target products;The CF₃-group might improve the reactivity of imine intermediates to facilitate 1,2-addition of m-CPBA as nucleophile and intermolecular oxidation to give 2-pyrrolidones.Moreover,the reaction could be easily prepared in gram scales and the obtained products were selectively converted into various pyrroline skeletons.In the third part,we studied a method for the selective construction of spiro[5.5]quinoline naphthalenedione compounds and spiro[4.5]quinoline naphthalenedione compounds through[4+3]cycloaddition/oxidative dearomatization cascade strategy.The reaction was carried out with N-aryl-α,β-unsaturated nitrones and 1-ethynylnaphthalen-2-ols as raw materials,DCM as the solvent and m-CPBA as oxidant.A total of 28 spiro[5.5]quinoline naphthalenedione compounds were synthesized in moderate to good yields and high diastereoselectivity.The reaction had simple operation,good functional group tolerance and wide range of substrates.It was found that a total of 19 spiro[4.5]quinoline naphthalenedione compounds were synthesized in moderate to good yields and high diastereoselectivity through oxidization and dearomatization with Ph I（OAc）₂ as oxidant by using N-trifluoromethylaryl-α,β-unsaturated nitrones and 1-ethynylnaphthalen-2-ols as raw materials.In the four part,we developed an available and recyclable sulfonated graphene oxide catalyzed[4+3]cycloaddition/[3,3]-rearrangement reaction of N-vinyl-α,β-unsaturated nitrones and 1-ethynylnaphthalen-2-ols to prepare various polysubstituted pyrrole derivatives.Compared with graphene oxide,sulfonated graphene oxide not only removed a large number of oxygen-containing functional groups from graphene oxide,but also had hydrophilicity.The high hydrophilicity of sulfonated groups improved the dispersion of carbon materials,while maintaining its original properties,reducing the accumulation of graphene,promoting catalytic reactions,and preparing pyrrole compounds with efficiently.In addition,sulfonated graphene oxide can be easily recovered and recycled seven times without lowering the catalytic efficiency.