Studies On The Application Of Isocyanides And Diazo/Sulfoxonium Ylides Reaction In Organic Synthesis

As an important class of organic synthetic substrates,isocyanides are widely used in organic,pharmaceutical,materials,and biochemistry,which are irreplaceable components of modern organic synthetic chemistry.Diazo compounds and their analogues（sulfoxonium ylides）are also a very important class of organic synthesis intermediates and play an extremely important role in organic chemistry and materials chemistry.Therefore,the application of isocyanides,diazo compounds and sulfoxonium ylides in organic synthesis has received extensive attention.However,in this field,studies on the reactions of isocyanides and diazo compounds are not only relatively few,but also mainly focused on various conversion reactions in which the ketenimine generated by the coupling reaction of them as the key intermediate and[3+2]cycloaddition reactions between them.In the other hand,the reactions between isocyanides with sulfoxonium ylides have not been realized.Therefore,the development of novel reactions between isocyanides and diazo compounds,especially the realization of tandem cyclization reactions of isocyanides with sulfoxonium ylides and the development of novel and efficient methods for the synthesis of heterocyclic compounds are highly anticipated.This thesis is based on the development of isocyanides in organic synthesis,focusing on the study of multiple novel reactions of isocyanides with diazo compounds/sulfoxonium ylides.The three-component reactions of isocyanides,α-diazo ketones with acid anhydride,the coupling reactions of isocyanides andβ-hydroxy-α-diazo carbonyl compounds,the tandem cyclization reactions of isocyanides with sulfoxonium ylides,and visible-light induced radical addition-cyclization reactions of o-alkenyl aryl isocyanides with thioethers have been investigated.The specific studies are as follows:1.A three-component tandem cyclization reaction of isocyanides,α-diazo ketones and acid anhydrides was achieved under the catalysis of Zn（OAc）₂.This reaction provides a novel and effective strategy for the construction of multisubstituted maleimides from simple and readily available substrates by constructing two C-C bonds,one C-N bond,and one C-O bond in a single step via sequential Wolff rearrangement/nucleophilic addition/intramolecular aza-cyclization reactions.The reaction has the advantages of inexpensive and readily available starting materials,three-component,one-pot,good to high yields,a wide range of substrates and good functional group tolerance.2.The first tandem cyclization reaction of isocyanides with sulfoxonium ylides was developed with the silver salt as a catalyst,and a series of 3-aminofuran or 4-aminoquinoline derivatives were synthesized efficiently.The above experimental results not only developed the new reaction of isocyanides with sulfoxonium ylides and provided a novel and efficient method for the synthesis of 3-aminofuran and 4-aminoquinoline in a single step;but also laid the foundation for the application research of the reaction of isocyanides with sulfoxonium ylides in organic synthesis.3.The nucleophilic addition reaction of isocyanides with alkenyl diazo cation precursors was successfully developed by usingβ-hydroxy-α-diazo carbonyl compounds as alkenyl diazo cation precursors and isocyanides as carbon nucleophiles in the presence of Lewis acids.The reaction efficiently constructed the quaternary carbon center in a single step from a simple and readily available substrates and synthesizedβ-carboxamido-α-diazo ketone or ester diazo compounds which are difficult to synthesize by conventional methods.In the further study,the transition metal-catalyzed intramolecular cyclization-rearrangement reactions ofβ-carboxamido-α-diazo carbonyl compounds were investigated,synthesizing methylene cyclohexane and various spirocyclicβ-lactams.Based on this,the tandem cyclization reactions of isocyanides withβ-hydroxy-α-diazo carbonyl compounds were realized in the presence of DBU,and a series of multi-substituted pyrrole derivatives were prepared.The series of research results not only developed new reaction type of isocyanides and diazo compounds,but also provided new ideas for the application ofβ-hydroxy-α-diazo carbonyl compounds as alkenyl diazo cation precursors in the organic synthesis.4.The radical addition/cyclization reaction of o-alkenyl aryl isocyanides with thioethers was achieved under visible light irradiation conditions by using Ru（2,2-bpy）₃PF₆as a photosensitizer.This reaction provides a new and effective strategy for the synthesis of a variety of 2-thioquinolines from readily available starting materials with a wide range of substrate scope in a single step.In addition,theα-C（sp³）-H activation reaction of thioether-containing amino acids was achieved under mild condition when they were used as starting materials,and quinoline derivatives containing thioether amino acid structures were synthesized.In view of the importance of thioether,amino acids and quinoline structures in biochemistry and medicinal chemistry,we believe that this reaction offers the possibility of subsequent modifications of thioether amino acids with biological and pharmaceutical activities.This series of research results not only provide a new method for the synthesis of thio-substituted and thioether amino acid-substituted quinolines,but also lay the foundation for further applications of photocatalytic reactions involving isocyanides for the synthesis of nitrogen-containing heterocyclic compounds.