Non-Noble Metal-Catalyzed Tandem Reactions Of Heterosubstituted Alkynes For The Synthesis Of Heterocycles

Heterosubstituted alkynes are special substituted-alkynes which consist of heteroatoms directly connected to acetylenic carbon.Compared with normal alkynes,heterosubstituted alkynes generally exhibit more highly polarized triple bonds due to the difference of electronegativity between heteroatoms and carbons.So the chemical reactivities of heterosubstituted alkynes are rather high.Generally,non-noble metal catalyzed reaction of heterosubstituted alkynes can be achieved.In addition,regioselective reversal can be realized when attacking of nucleophile to the triple bonds.More important,the heteroatoms in heterosubstituted alkynes can be introduced into target heterocycles to achieve the diverse synthesis of useful heterocycles.Therefore,the studies of heterosubstituted alkynes have been attracted significant attention in the past decade.Heterocycles are widely existed in natural products and pharmaceutical bioactive molecules.Among them,N-heterocycles,O-heterocycles and S-heterocycles account for most of the proportion in heterocycles.Therefore,this dissertation will focus on three types of electron-rich heterosubstituted alkynes containing ynamides,ynol ethers and thioynol ethers.To construction of valuable heteocycles by realizing non-noble metal catalyzed tandem reaction of these heterosubstituted alkynes.It not only can enrich the heterosubstituted alkyne chemistry,but also provides new synthetic strategies for the construction of core skeletons of natural products and pharmaceutical bioactive molecules.This dissertation is mainly divided into the following four sections:In the first part,the recent research progress of heterosubstituted alkynes and reaction of alkynes and isoxazoles are briefly introduced.The applications of electrocyclization in organic synthesis are described.On the basis of analysis and summary of background,the main design ideas and research purposes of this dissertation are proposed.In the second p art,zinc-catalyzed amination reaction of heterosubstituted alkynes with isoxazoles,which include reaction of ynol ethers and thioynol ethers are studied.Non-noble metal catalyzed reactions of ynol ethers or thioynol ethers with isoxazloes are achieved,which represents the first example of non-noble metal catalyzed reaction of alkynes and isoxazoles.For the ynol ethers,1H-pyrrole and 3H-pyrrole can be selectively obtained by controlling different types of substituted isoxazoles.For the thioynol ethers,?-keto enamides are delivered only,which could be readily converted to four types of valuable heterocycles.Combined with DFT calculation,a novel reaction pathway is proposed.In comparison to traditional noble-metal catalysis,this zinc-catalyzed reaction system did not go through traditional ?-imino metal carbene intermediates.At the same time,the source of the regioselectivity is clarified.In the third part,zinc-catalyzed asymmetric 6? electrocyclization reaction of ynol ethers with isoxazoles is introduced.For the first time,a zinc-catalyzed asymmetric[4+3]annulation via 6? electrocyclization is achieved,which can construct a series of chiral 2H-azepine compounds.This protocol not only represents the first asymmetric reaction of isoxazoles with alkynes,but also represents the first asymmetric catalysis based on ynol ethers and the first asymmetric heptatrienyl cation type 6? electrocyclization.DFT calculations provide further evidence for the feasibility of the proposed reaction mechanism,especially in clarifying the origins of regioselective and stereoselective control of the reaction.In the fourth part,copper-catalyzed asymmetric alkenyl metal carbene cyclization of diynes is studied.Based on previous work in our group,we choose propargyl enynamides as the substrates.After generation of copper carbenes,it would be readily trapped by intramolecular alkene moties to synthesis chiral polycyclic heterocycles via an asymmetric alkenyl metal carbene cyclization progress.This work represents the first non-noble metal catalyzed asymmetric C-H functionalization/cyclization involving alkenyl metal carbene,which provides a new strategy to construct chiral polycyclic pyrroles in high yields with excellent enantioselectivities.