Domino Reaction For Construction Of Nitrogen-containing And Sulfur-containing Heterocyclic Compounds

Heterocyclic compounds containing nitrogen,sulfur and oxygen are widely used in pesticides,medicines and materials[1-2],They are the core structure fragments of many drugs or natural alkaloids[3],and showed high biological or medicinal activities in many aspects[4],more and more researchers are increasingly interested in the synthesis of heterocyclic compounds.There are many possibilities for series reactions,making the reaction very important in heterocyclic chemistry and medicinal chemistry.Therefore,the series reaction has become a very hot research topic in current drug research and development.In this paper,some series reaction were investigated to construct nitrogen-containing and sulfur-containing heterocyclic compounds,Finally,a series of potentially biologically active tetrahydroimidazo[1,2-a]pyridine,the polysubstituted thiophene derivatives,functionalized spiro[indoline-3,2'-naphthalene]-4'-yl acetates and alkoxy-substituted spiro[benzo[h]chromene-5,3'-indolines were successfully synthesized.1.In the presence of triethylamine,the addition reaction of substituted a-amino acid alkyl esters including ethyl hyperphenylalaninate,phenylalaninate,isoleucinate,and alaninate with dialkyl but-2-ynedioate afforded active ?-enamino esters,which in turn reacted with aromatic aldehydes and malononitrile to give tetrahydroimidazo[1,2-a]pyridine derivatives in moderate yields.Under similar reaction conditions,the reaction of ethyl glycinate with dialkyl but-2-ynedioate resulted in a 1,3-dipolar azomethine ylide,which reacted further with in situ-generated arylidene malononitrile,alkyl cyanoacetate,and cyanoacetamide to give polysubstituted pyrrolidine derivatives in good yields The structures of the synthesized new compounds were characterized by IR,1H NMR,13C NMR,HRMS,etc.,and the single crystal molecular structure of 7 compounds was determined by single crystal diffraction.2.The one-pot four-component reaction of aromatic aldehydes,malononitrile,1,3-thiazolidinedione and ethyl glycinate hydrochloride in ethanol in the presence of triethylamine afforded trans-dihydrothiophene ureidoformamide derivatives in moderate to good yields.The other a-amino acid ethyl esters resulted in the corresponding diastereoisomeric dihydrothiophene derivatives with various molecular ratios.The functionalized thiophene derivatives were also successfully prepared by sequential dehydrogenation reaction with DDQ.The structures of the synthesized novel compounds were characterized by IR,1H NMR,13C NMR,HRMS,etc.,and the single crystal structure of 3 of them was determined.3.The three-component reaction of two molecular N-phenacylpyridinium salts with indane-1,3-dione and N-alkylindoline-2,3-diones in dry acetonitrile in the presence of triethylamine resulted in the unique functionalized spiro[indoline-3,4'-naphtho[1,2-b]furan]derivatives in good yields,which were successfully converted to stable spiro[indoline-3,2'-naphthalen]-4'-yl acetates derivatives by acylation with acetyl chloride in methylene dichloride and stable alkoxy-substituted spiro[benzo[h]chromene-5,3'-indolines]by acid catalyzed etherification reaction in alcohol.The reaction mechanism involved the sequential cycloaddition reaction of the in situ of pyridinium ylide to enone,ring-opening of 1,3-indanedione,and selective annulation process.The structures of the synthesized new compounds were characterized by IR,1H NMR,13C NMR,HRMS,etc.,and the single crystal structure of 3 of them was determined.