Studies On Cascade Difunctionalization/Cyclization Of Alkenes And Alkynes:Synthesis Of Five-membered Heterocyclic Compounds

The difunctionalization reaction of alkenes and alkynes,as one of efficient methods to construct carbon-heteroatom and carbon-carbon bonds,has received wide attentions in organic synthesis.Part of the methodology studies have been applied in the synthesis of natural products and biological active molecules.In view of the research meaning and practical applicative values,the difunctionalization of alkenes and alkynes will be briefly discussed.This thesis focused on the corresponding tandem cyclization reactions,which participated in the efficient synthesis of five-membered cyclic compounds.As the further study,an research for the strategy of six-membered nitrogen-cyclic compounds with alkynes is explored preliminarily.The specific contents include the following four chapters.Cascade cyclization reactions,as an important research area in organic methodology,provide a powerful method to access(hetero)cyclic molecular frameworks in a one-pot reaction fashion.It is a long-term challenge for organic chemists to explore and develop high efficient,excellent chemoselective,low cost and waste-minimizing processes of general applicability that should improve our attention on strategy researches.Chapter 1: The 1,2-dicarbofunctionalization/cyclization of alkenes or alkynes is an appealing method for the synthesis of valuable(hetero)cyclic compounds via thermocatalysis and photocatalysis amenable to a single operational fashion.The advantages of this synthetic strategy captures chemists’ interests,as the protocol can prepare an array of cyclic skeletons and generate structurally diverse molecular complexity at the same time.The functionalized cyclic motifs can serve as versatile building blocks for further structural elaboration.Over the past few years,continuousresearch has successfully extended the scope of manifold cyclic products with numerous elegant versions.The thermocatalysis and photocatalysis exhibit different features in the cascade 1,2-dicarbofunctionalization/cyclization reaction.Scientific researches in the field of thermocatalysis are relatively diverse and extensive.As background knowledge,the second section in this chapter focuses on the outstanding achievements in the construction of five-membered(hetero)cyclic compound with or without N and O elements via thermocatalysis.Increased attentions have being placed on visible-light-mediated photoredox processes for several advantages apparent in the context of low consumption of reactive materials,ease of execution and mild reaction conditions,which meet the requirements of "green chemistry".In recent years,visible-light photocatalysis has obtained considerable momentum for providing carbon-centered radical intermediates via single-electron transfer processes(SET),and occupied a privileged position to achieve cascade cyclization reaction.The reduction of halohydrocarbon to form a variety of radical intermediates is one of the most effective processes for accessing chemical activation,which has broad scope for application in carbo-and heterocycle synthesis.In the third section,we elaborate on achievements in previous researches of halogenated hydrocarbons and described such photoinduced catalysis in detail.Chapter 2: A palladium-catalyzed cascade difluoroalkylation/cyclization process of N-propargylamides has been developed.This strategy constructs a series of oxazoles and oxazolines with broad functional-group tolerance and introduces difluoromethyl groups into heterocycles in a one-pot fashion.The system uses a carbonyl oxygen as the acceptor for the addition of a vinylpalladium intermediate to achieve the cyclization.Oxazoline derivatives are generated as the Z-isomer with high stereoselectivity.Additionally,we validated the tentative mechanism of this reaction.Chapter 3: In the third chapter,a palladium-catalyzed,photochemical tandem cyclization/ dicarbofunctionalization of unactivated alkyl halides containing an alkene moiety offers an appealing route to produce five-membered rings in a redox-neutral fashion.Multisubstituted carbo-and heterocyclic compounds were prepared through the formation of new C–B or C–O bonds,which provides a convenient synthetic route for further transformations.This protocol is characterized by the reaction of alkene regio-and stereoselectivities,good functional group compatibility,wide substrate scope,and mild reaction conditions.Chapter 4: An efficient cobalt-catalyzed difluoroalkylation/radical conjugatecyclization manifold with halogenated fluorinating reagent and O-azido phenylpropargyl alcohol is accomplished under mild reaction conditions,thus providing an remarkable route to fluorinated quinoline compound.We have made the staged progress in the steps of reaction researches.Further studies to explore the derivative reactions as well as to define the mechanism are currently underway in our laboratory.