Study On The Visible Light-Promoted Oxyalkylation Reaction Involving Cyclic Ethers

Cyclic ethers,such as tetrahydrofuran(THF),1,4-dioxane and tetrahydropyran(THP),are important structural motifs widely found in natural products and synthetic drugs.These compounds have a wide range of biological activities,including antibacterial,anti-inflammatory,anti-cancer and anti-diabetes properties.In particular,tetrahydrofuran and 1,4-dioxane are used not only as solvents in organic synthesis,but also as raw materials for the synthesis of some complex molecules,the conversion of simple cycloethers into useful molecules has been of great interest to many chemists.In the past ten years,chemical workers have widely used cyclic ether to synthesize a series of organic molecules,and great progress has been made in the aspects of α-arylation、α-alkylation、α-enylation and α-amidation of cyclic ethers.In this thesis,we aim to focus on the cascade free radical cyclization/oxidation reaction and thioetherification reaction of cyclic ethers to construct a variety of C-C and C-S bond compounds.This thesis consists of the following four chapters:Chapter 1 Research progress in organic synthesis involving cyclic ethersIn this chapter,the research progress of organic synthesis reactions involving cyclic ethers is summarized from three aspects: metal catalytic synthesis,metal-free catalytic synthesis,visible light catalytic synthesis.Chapter 2 Copper-and visible light-catalyzed cascade radical cyclization of Npropargylindoles with cyclic ethersAn efficient visible light-assisted,copper-catalyzed tandem radical cyclization of N-propargylindoles with cyclic ethers was established.A serial of 2-oxoalkyl-9Hpyrrolo[1,2-a]indol-9-ones with potential biological activities were synthesized in middle yields by using a dual catalytic system with copper acetate as a transition metal catalyst and eosin Y as a visible light catalyst.Unfortunately,the dioxane can not provide the corresponding target product.The method has mild reaction conditions,simple operation,green economy and good functional group tolerance.The investigation of reaction mechanism shows that it goes through a cascade oxoalkyl radical addition,cyclization and oxidation process.Chapter 3 Thioetherization of cyclic ethers with aryl thiophenols under visible light irradiationA method to construct 2-phenylthio-tetrahydrofuran derivatives using eosin Y disodium salt as photosensitizer,tert-butyl hydrogen peroxide as oxidant,and 36 W blue LED as visible light source is developed.Twenty-one target compounds were prepared and obtained the products in 53-94% yields.The method has mild conditions,simple operation,green and high efficiency.The target product is obtained by free radical coupling reaction of aryl thiophenols and cyclic ethers as free radical precursors,and the yield is up to 94%.The method shows a wide range of substrates.Aryl thiophenols with different substituents can well participate in the reaction with various cyclic ethers.However,under standard conditions,the alkyl chain thiophenol can not be successfully involved in the reaction.On the basis of a series of control experiments,the prossible free radical mechanism is presented.Chapter 4 Summary and perspectiveIn summary,the oxygen alkylation reaction of cyclic ether with N-propargyl indoles or aryl thiophenols is mainly realized by photocatalysis,and the synthesis of2-oxoalkyl-9H-pyrrolo[1,2-a]indole-9-ketones and 2-phenylthio-tetrahydrofuran derivatives under different conditions can be obtained as expected products in moderate to excellent yields.These two reactions have the advantages of green economy,mild conditions,simple operation and wide range of substrates.They are feasible and reliable preparation methods.In addition,based on some control experiments and published literatures,we have made relevant research on the possible mechanism of the reaction.In the future work,we will further explore the application of cyclic ether in organic synthesis,with a view to developing new reactions and new methods related to cyclic ethers.