Preparation And Reactivity Of Multi-substituted Cyclohexyne Precursor

Angle-strained cycloalkynes are one kind of highly active compounds or intermediates containing an acetylenic bond.Due to the inherent reaction characteristics of the triple bond,cycloalkynes could simultaneously achieve ortho-bifunctionalization,such as cyclization reaction or ? bond insertion,which is difficult to achieve by other methods and own important synthetic significance.Among them,the most studied is benzyne,which was introduced in 1927 as a reactive intermediate.Since then,benzyne has been widely used in the functionalization of aromatic rings as well as in the synthesis of natural products,drugs and functional materials.Especially,the development of mild preparation conditions by Kobayashi and Hoye significantly improved the reaction efficiency and functional group compatibility of benzyne chemistry.In addition,these mild conditions inspire the discovery of numerous new transformations and propel the advance of benzyne chemistry.Although cyclohexyne possesses the same ring size and presented time as benzyne,unfortunately,the research on it is far behind the latter.In its early stage,due to the harsh preparation conditions of cyclohexyne,i.e.strong bases or high temperature,both the reaction efficiency and functional group compatibility were greatly restricted.However,with the application of mild generation conditions such as Kobayashi conditions,this problem could be well solved.Nowadays,one of the remaining limitation in cyclohexyne chemistry is the functionalization on the other four positions except the triple-bond.Therefore,this dissertation is focused on the preparation of polyfunctional cyclohexyne precursors and the study of their reaction behavior.As both cyclohexyne and benzyne could be prepared by the Kobayashi's method,especially under the circumstance that the preparation of Kobayashi benzyne precursor is convenient,we propose an idea by converting Kobayashi benzyne precursor to polysubstituted cyclohexyne precursor.Through continuous experimentation,the hydroxy-substituted Kobayashi benzyne precursors can be converted to polysubstituted cyclohexyne precursors via oxidative dearomatization operation.Those obtained cyclohexyne precursors can further undergo functional group conversion,where both TMS and OTf groups were unaffected.Subsequently,we studied the reactivity of these cyclohexyne precursors.Under the action of the activating reagent,these cyclohexyne intermediates can be smoothly generated and achieve subsequent reactions in high yields and selectivity,such as nucleophilic reaction,pericyclic reaction,etc.Finally,this dissertation also realized the reaction of cyclohexyne with arylallyl sulfoxide substrates.Through a tandem process,this chemical transformation can introduce a nucleophile and two electrophiles on the triple bond simultaneously and the acetylene bond is degraded to a saturated bond in one step,which could not be reached by traditional benzyne chemistry.This reaction shows that the chemical reaction characteristics of cyclohexyne is differed from benzyne,which exhibits a new idea for the future research on cyclohexyne chemistry.