Free-Radical-Reaction-of-Diisopropyl-Xanthogen-Dis

HETEROCYCLES,VoL48,NO.10,19982W3IFREERADICALREACTIONOFDIISOPROPYLXANTHOGENDISULFIDEWITHUNSATURATEDSYSTEMSYvesGareau*andAndrBBeaucheminMerckFrosstCentreforTherapeuticResearch,P.O.Box1005,Pointe-Claire-Dorval,Quebec,Canada,H9R4P8.Abstract-1,3-Dithiol-2-onesarepreparedinonepotreactionfromcommerciallyavailablediisopropylxanthogendisulfide(2)andalkynesunderradicalconditions.The5-memberedheterocycleisfomedviaaringclosureofvinylradical(7)resultingfromthethioradicaladditionof5toanalkyne.ThereactionworkedbestforalkynesconjugatedwithaC%doublebond.Theoxygenatomsofreagent(2)couldbereplacedbysulfurandthisnewreagentfurnished1,3-dithiol-2-thionesunderradicalconditions.INTRODUCTIONTetrathiafklvalenesarekeyconstituentsintheformationofchargetransfercomplexeswithmetallikepropertiesand1,3-dithiol-2-ones(1)areimportantbuildingblocksintheirpreparations.IbThese5-memberedheterocyclescanbepreparedinnumerouswayswhichusuallyrequiremanysteps?Ourcontributioninthisareahasbeenthesubjectofarecentcommunication,wherewedescribedabimolecularone-potreactionbetweendiisopropylxanthogendisulfide(2)andalkynesunderradicalconditions?Thismethodologydirectlyfurnishedcompoundsoftype(1).Withthisapproach,oneavoidedtheneedtoprepareS-propargylxanthogenoftype(3)foreveryalkyneused.Tofurtherdeveloponthismethod,hereinwewishtodemonstratei)that2isausefulsyntheticreagenttotransferthe1,3-dithiol-Zonefunctionality,ii)thescopeandlimitationsofthistransferreactionwithalkynesandalkenesandiii)theflexibilityofreagent(2)tobemodifiedwithdifferentcombinationofheteroatomstoallowthetransferofotherfunctionalitysuchas1,3-dithiol-2-thione.RESULTSANDDISCUSSIONWepreviouslyreportedthatterminalalkynescouldbeconvertedto1ina0.1Mrefluxingbenzenesolutionwith2andABN?Thisradicalreactionmaybedescribedbythethreemainstepsof2004HETEROCYCLES,Vol.48,No.10,1998atypicalradicalprocess(Scheme1).ThefirststepwastheinitiationeventwiththethermaldecompositionofacatalyticamountofAIBN.Theradical(4)thusgeneratedwouldaddtothecarbon-sulfurdoublebondof2togiveradical(5)andaneutralspecies(6).Additionof5onthelesshinderedsideofthetriplebondfollowedbyacyclizationgivesthedesiredheterocycle(8).Forthissequencetobevalid,thelaststepmustbeaccompaniedbytheextrusionofanisopropylradical(9).Atthispoint,thepropagationstepwouldbemainlycontrolledbytheadditionof9onxanthogen(2).Asfortheterminationstep,manypossibilitiescouldoccursuchasthecouplingof5witheither4or9.Thisscenariowasstronglysupportedbyexperimentalevidence.Alongwith8,compounds(6)and(10)havebeenisolatedandcharacterizedfromthereactionmixtures.SchemeIinitiation:propagation:5+ReR*S-SL+w.7k='R899+2-5+AoAsAI0termination:5+9-10R'=isopropyl5+4-6Theisopropylgroupofxanthogen(2)alsoprovedtobeimportantforcompletionofthereaction.Fragmentationofxanthogenscontainingprimaryakylgroupshasbeenreportedtobeslowcomparedtosecondaryanalogues.Thisdifferenceinratewasdirectlyreflectedinalowrecoveryof8whendiethylxanthogendisulfidewasused.Underthesameconditions,phenyacetyleneanddiethylxanthogendisulfidefurnisheda36%yieldof4-phenyl-1,3-dithiol-2-one.Atfirst,thereactionswererunina1.0Mbenzenesolutionwithrespecttothealkyneandappreciableamountsofsideproductswereisolated.Theseproductswereidentifiedasdouble-additioncompoundsofgeneralstructure(ll),andprobablyarosefiomtheadditionofintermediate(7)tounreactedxanthogen(2).MixturesofEandZisomerswerecharacterizedinthecaseofphenylacetylene(lla),m-HETEROCYCLES.Val.48.No.10.19982005methoxyphenylacetylene(Ilb)ando-bromophenylacetylene(llc).However,theamountofthesecompoundscouldbegreatlyreducedbydecreasingtheconcentrationofthereactionmixture.Whentheexperimentwasconductedat0.1M,onlytracequantitiesofthesesideproductsweredetected./R\11R=a-phenyl(4%.3.311,En)b-m-rnethoxyphenyl(5%.3.211.EIZ)c-o-brornophenyl(16%.4.911,ER)Withtheoptimizationofthereactionconditionsandofreagent(2),weturnedourattentionatinvestigatingthescopeandlimitationsofthismethod.Severalalkynesweresubmittedtoastandardsetofconditions(1.0equivalentofalkyne,1.1equivalentof2and0.45equivalentofAIBNina0.1Mrefluxingbenzenesolution)andtheresultsarereportedinTable1.Fromthenumerousalkynesstudied,atrendinreactivitycouldbeobservedbasedonthea-substitutionandonecanclassifythesubstratesintotwocategories.Thefirstcategoryofsubstratescontainsmonosubstituted(andsomedisnbstituted)alkynesconjugatedeitherwithanaromaticringoranolefin.Substitutionpatternaswellasfunctionalityonthearomaticringhadlittleeffectontheoutcomeofthereaction.Thiscategoryfurnishedthebestyieldsof8.Theremainingalkynesfallintothesecondcategory.Thisincludesaliphaticalkynes,bulkydisubstitutedalkynesandthoseconjugatedwithacarbonylgroup.Theconjugationwithacarbonylgroupresultedinalowyieldof8andalowrecoveryofstartingmaterial.Inasimilarway,aliphaticalkynesgaveunexpectedlowyieldsbut,contrarytothecarbonylcase,withahighrecoveryofstartingmaterial.Torationalizethedifferentbehaviorbetweenthetwocategoriesofalkynes,therelativestabilityandthegeometryofradical(7)maybeinvoked.Theadditionofathioradicaltoanalkynesisareversibleprocesdandtheresultinghighenergyvinylradicalcanadopton