Transition Metal-Catalyzed Tandem Cyclization Reactions Of Heterosubstituted Alkynes For The Synthesis Of Heterocycles And Polycyclic Compounds

Alkynes are a very important kind of synthons in organic synthesis,which can undergo various types of addition reactions under the activation of transition metal?-acids or Bronsted acids to realize the highly efficient construction of C-C,C-H and C-X bond.Due to the fact that the heteroatom is able to impose an electronic bias,it not only can enhance the activity of alkyne,but also can realize the regioselectivity control of cycloaddition reaction.More importantly,Heterosubstituted alkynes are easier to be trapped by the nucleophiles in the presence of transition metals to form extremely useful metal carbenes intermediates.This paper will be devoted to study transition metal-catalyzed tandem cyclization reactions of heterosubstituted alkynes and explore the new method of formation of metal carbenes to realize multistep cascade reaction in the presence of various functional groups.On this basis,we design and develop some non-noble metal catalyzed tandem cyclization reactions to provide new synthetic methods for bioactive molecules containing core skeleton of drugs and enrich the synthetic methodology of organic chemistry.This dissertation is divided into the following four sections mainly:In the first part,the reaction background and research progress of ynamides with isoxazoles,pyridine N-oxides,azides are briefly introduced.We find out the unsolved problems in this field through the analysis and research of the reported literature.On the basis of above mentioned background,the main research ideas and innovation points of this paper are put forward.In the second part,platinum-catalyzed formal[5+2]and[4+2]annulation of isoxazoles with heterosubstituted alkynes are introduced.A novel and atom-economical route to the generation of ?-imino platinum carbenes through a platimum-catalyzed annulation reaction between ynamides and isoxazoles is studied.This work provides the first example of the generation of aimino platinum carbenes which is dramatically divergent from that observed under gold catalysis.Besides the efficient and atom-economical formation of valuable 1,3-oxazepines and 2,5-dihydropyridines,a computational study provides further evidence for the feasibility of the proposed mechanism.In the third part,copper-catalyzed oxidation reaction of diynes are introduced.The oxidation reaction of heterosubstituted substituted alkynes which is connected with alkyne and azide group is studied.This is the first example of non-noble metal-catalyzed diyne oxidation by an N-O bond oxidant.At the same time,this is the first example that metal carbenes produced by alkyne oxidative pathway are trapped by azide group.A series of complex nitrogen-containing heterocyclic molecules containing core skeleton of a drug are constructed efficiently.In addition,the gold-catalyzed cascade cyclization of the same substrates leads to the formation of pyrrolo[2,3-b]indoles.Moreover,the computational study provides further evidence on the feasibility of the proposed mechanism of these novel cascade reactions,especially for the distinct selectivity.In the fourth part,copper-catalyzed amination reaction of heterosubstituted alkynes are introduced.The generation of a-imino copper carbenes via non-noble metal-catalyzed intramolecular reaction of azides and ynamides is the first time to be disclosed.The ?-imino copper carbenes can be trapped by different nucleophilic reagents to build a series of isoquinoline compounds.