Jun-KeWang,Ying-XiaoZong,Xi-CunWang,Yu-LaiHu,Guo-RenYue.SynthesisofN-benzothiazol-2-yl-amidesbyPd-catalyzedC(sp2)-Hfunctionalization[J].CCL,2015,26(11):1376-1380SynthesisofN-benzothiazol-2-yl-amidesbyPd-catalyzedC(sp2)-HfunctionalizationJun-KeWanga,b,c,Ying-XiaoZonga,b,Xi-CunWanga,b,Yu-LaiHua,b,Guo-RenYueaaKeyLaboratoryofHexiCorridorResourcesUtilizationofGansuUniversities,CollegeofChemistryandChemicalEngineering,HexiUniversity,Zhangye734000,China;bGansuKeyLaboratoryofPolymerMaterials,CollegeofChemistryandChemicalEngineering,NorthwestNormalUniversity,Lanzhou730070,China;cGansuEngineeringLaboratoryofAppliedMycology,HexiUniversity,Zhangye734000,ChinaReceived11May2015,Receivedinrevisedform29June2015,Accepted1July2015,Availableonline10August2015.E-mailaddresses:wangxicun@nwnu.edu.cn;huyulai@126.comAbstract:AcatalyticsynthesisofN-benzothiazol-2-yl-amidesfrom1-acyl-3-(phenyl)thioureaswasachievedinthepresenceofapalladiumcatalystthroughtheC(sp2)-Hfunctionalization/C-Sbondformation.ThissyntheticmethodologycanproducevariousN-benzothiazol-2-yl-amidesinhighyieldswithgoodfunctionalgrouptolerance.Keywords:BenzothiazolePd-catalyzed1-Acyl-3-phenylthioureaC-HfunctionalizationL-Proline1.IntroductionThebenzothiazolemoietyisanimportantscaffoldduetoitswidespreadoccurrenceinbioactivenaturalproducts,pharmaceuticals,organicoptoelectronicmaterials,andligandsforphosphorescentcomplexes[1-4].Inparticular,substitutedNbenzothiazol-2-yl-amidesareanimportantclassofheterocycliccompoundsthatexhibitawiderangeofbiologicalproperties[5-9]suchasubiquitinligaseinhibition[5],antitumor[6],antirotavirusinfections[7],modulatingtheadenosinereceptor[8,9],andthenuclearhormonereceptor[9].Forexample,theN-benzothiazol-2-yl-cyclohexanecarboxamide,asanewanticancerdrug,wasselectedasoneofthemostpromisingscreeninghitcompounds(Fig.1)[6].Theacylationreactionfrom2-aminobenzothiazole,oneoftheclassicalmethodsforthepreparationofthesemolecules[5,6],isknownforthelimiteddiversityofthecommerciallyavailablestartingmaterials.Furthermore,thepreparationof2-aminobenzothiazolealsorequiredtheuseofthetoxicbromine.ThepastseveralyearshavewitnessedthegreatprogressinthedevelopmentoftheC-Sbondformationpromotedbytransitionmetals,whichcanprovidemoreefficient,practical,andstraightforwardapproachestovaluablesulfur-containingcompounds[10,11].However,thesemethodshavebeenmainlyfocusedonthe‘‘traditional’’cross-couplingreactionsofArX(X=Cl,Br,I,OTf,andB(OH)2)andsulfides[12-39].ToachievegreenerandmoreatomeconomicC-Sbondformations,transitionmetal-catalyzeddirectoxidativecross-couplingofC-Hbondsandsulfideswouldbeideal[40-47].Inourpreviouswork,wehaveshownthatN-benzothiazol-2-ylamidescanbesynthesizedsmoothlybyCu-catalyzedintramolecularcyclizationofvarioussubstituted1-acyl-3-(2-bromophenyl)thioureas[48].ThismethodcanprovidemorediversiformNbenzothiazol-2-yl-amidesthroughthecarbon-heteroatomformationunderrelativelymildconditionsandavoidtheuseofthetoxicbromine.However,thedrawbackofthisprocedureisthelimiteddiversityofthecommerciallyavailablestartingmaterialsduetotheuseofsubstitutedortho-haloarylamines.InordertofurtherextendthediversityofN-benzothiazol-2-yl-amides,wehaverecentlydemonstratedanefficientintramolecularcyclizationofsubstituted1-acetyl-3-(2-phenyl)thioureacatalyzedbyironthroughC-Hfunctionalization[49].ThismethodcanprovidemorediversiformN-benzothiazol-2-...
