Syntheses Of Pyran,Pyridazine And Pyrrolidine Compounds From 1-Chlorocyclopropanecarboxylates

Nitrogen-and oxygen-containing heterocyclic structures are widely used in drugs,natural products and materials.Therefore,chemists have developed efficient,green and economical methods to synthesize heterocyclic compounds with important applications.Thesis,the synthesis of heterocyclic compounds with important dominant structural units is studied by developing new reactions between in situ electron-deficient cyclopropene intermediates and various nucleophiles.The main works include the following three parts:1)the investigation of the reactions of electron-deficient cyclopropene intermediates with sulfoxide ylides and sulfur ylides;2)the investigation of the reactions between electrondeficient cyclopropene intermediates and various hydrazone compounds;3)the investigation of the reactions of electron-deficient cyclopropene intermediates with triphenylphosphine,and their four-component tandem reactions with formaldehyde and amine compounds.Through the above dissertation,we expanded the structural diversity synthesis methods starting from electron-deficient cyclopropylene intermediates,and constructed three kinds of functionalized N-or O-heterocyclic compounds.The main works of thesis are divided into the following five chapters:In the first chapter,the research background and research ideas are briefly introduced.This part mainly focuses on the reactions starting from highly strained cyclopropane or cyclopropene compounds,and their application in synthesis of three-,four-,five-,six-,and seven-membered heterocyclic structures and recent progress in this field.On this basis,the designed preliminary ideas and research contents for thesis are suggested.The main dissertation is focused on the development of reactions between alkyl 2-aroyl-1-chlorocyclopropanecarboxylates and various nucleophiles and the construction of structurally diverse heterocyclic compounds.In the second chapter,the reaction of 1-chlorocyclopropanecarboxylate with trimethyl sulfoxide iodide was introduced.The two reactants are smoothly converted into cyclopropene intermediate and sulfoxide ylide intermediate under the promotion of combined base,respectively.The reaction readily proceeded at room temperature to afford2,5-substituted 4H-pyran compounds in 49-92% yield.When 3-substituted 1-chlorocyclopropanecarboxylates are used as the substrates,2,4,5-trisubstituted 4H-pyran compounds are obtained in 55-92% yields in the presence inorganic base cesium carbonate under heating conditions.In the third chapter,the reaction of 1-chlorocyclopropanecarboxylates with acylmethylthio salts is described.Under the promotion of cesium carbonate,the two reactants are converted into cyclopropene intermediates and sulfur ylide reagents under heating conditions respectively,and their subsequent reaction gives 3,5,6-trisubstituted 4H-pyran compounds in the yields of 35-81%.Changing the structure of 1-chlorocyclopropane substrates,we can obtain 3,4,5,6-tetrasubstituted 4H-pyran compounds and 2,3,4,5,6-pentasubstituted 4H-pyran compounds in satisfactory yields.The results of parallel experiments clearly show that each of the two reactants has the tendency to undergo background self-reaction under the reaction conditions.Therefore,this is a successful case for selective control reaction.In the fourth chapter,the reaction of 1-chlorocyclopropanecarboxylate with simple hydrazone compounds is introduced.The reaction was carried out in the presence of cesium carbonate at room temperature,affording a class of 3,5,6-trisubstituted tetrahydropyridazine derivatives in high yields.Through screening of the reaction conditions,the dr values for the reaction can be significantly improved.It is found that the configuration of syn-isomer can be converted into anti configuration in alkali methanol solutions.In addition,with DDQ as oxidant,tetrahydropyridazine products are easily oxidized into pyridazine compounds in good yields.In the fifth chapter,the reaction of 1-chlorocyclopropanecarboxylate with neutral nucleophile triphenylphosphine is introduced.Under the promotion of cesium carbonate,the 1-chlorocyclopropane substrate and triphenyl phosphine can react successfully to form triphenyl phosphine ylide.In further derivatization process of triphenyl phosphine ylide,we not only established a three-components cascade reaction between 1-chlorocyclopropanecarboxylate,triphenylphosphine and formaldehyde,which gives high yields of multifunctional dienes,but also successfully implemented a four-components cascade reaction between the substrate,triphenylphosphine,formaldehyde and amines,which furnishes good yields of pyrrolidine compounds.The above research demonstrates that the electron-deficient cyclopropene intermediate generated in situ from 1-chlorocyclopropanecarboxylate under the basic conditions is a kind of valuable synthon,and it can smoothly react with various common nucleophiles via cascade nucleophilic addition,ring opening of cyclopropane and intramolecular ring closure reaction.This reaction mode provides us a new synthetic way for the construction of different types of heterocyclic skeletons.