TransitionMetalFree C(sp2)—H Phosphorothiolation Cyclization of oHydroxyarylenaminones Access to S3Chromon Phosphorothioat.docx

Synthesis&Cata1ySiS*W)Checkforupdatesdoi.org10.1002adsc.202300089Transition-Meta1-FreeC(sp2)HPhosphorothio1ationZCyc1izationofO-Hydroxyary1enaminones:AccesstoS-3-ChromonPhosphorothioatesBiaoZhang,+aZhonghuiFu,+aHaoqiYang,aDonghan1iu,aYu1inSun,aYuXu,cFuchaoYu,，*andSheng-JiaoYank*aFacu1tyof1ifeScienceandTechno1ogy,KunmingUniversityofScienceandTechno1ogy,Kunming,650500,Peop1e'sRepub1icofChinaE-mai1:yufuchao05bKey1aboratoryofMedicina1ChemistryforNatura1Resources,Ministrj,ofEducationandYunnanProvince,Schoo1ofChemica1ScienceandTechno1ogy,YunnanUniversity,Kunming650091,Peop1e,sRepub1icofChinaE-mai1:yansjcSchoo1ofnursing,Xi,AnInnovationCo11egeofYan,AnUniversity,Xi,An,710100,Peop1e'sRepub1icofChinaB.ZhangandZ.Fucontributedequa11ytothiswork.Manuscriptreceived:January26,2023;Revisedmanuscriptreceived:March6,2023;Versionofrecordon1ine:March29,2023QSupportinginformationforthisartic1eisavai1ab1eontheWWWunderhttps:/doi.org/10.1(X)2adsc.2023()0089Abstract:TheC(SP?)Hphosphorothio1ationinvo1vingcyc1izationprocessthroughatransitionmeta1-freestrategyisreported.Itprovidesanattractiveapproachfortheconstructionva1uab1e53-chromonphosphorothioatesfromo-hydroxyary1enaminonesandP(O)SHcompoundsinthepresenceof1.0equiv.ofiodineat60.Thisnove1protoco1showsreadi1yavai1ab1echemica1s,broadsubstratescope,andmi1dreactionconditions.Keywords:Phosphorothio1ation;o-Hydroxyary1enaminones;S-3-Chromonphosphorothioates;Transition-meta1-freePhosphorothoates,whichcontaintheSP(O)(O)2moiety,havereceivedconsiderab1eattentionduetotheirprominentbio1ogica1propertiesinagrochemica1sandpharmaceutica1s.111Inaddition,theyhavea1sofunctionedasusefu1bui1dingb1ocksinorganicsynthesisinvo1vingtheformationofCS,CC,andCFbonds.Consequent1y,thedeve1opmentofefficientapproachesforconstructingphosphorothioatesisstrong1ydesired.Amonga11ofthesyntheticmethodsaccesstophosphorothioates,mostofapp1icationsareimp1ementedthroughthefo11owingsixsyntheticStrategies(Scheme1a):(1)theMichae1is-Arbuzov-typereactionofsu1fony1ha1ides,su1feny1ha1ides,disu1fidesorotherderivativeswithP(O)Hcompounds;(2)thecondensationofthio1swithphosphoroch1oridatesorPhosphorobromidates;141(3)theoxidativecrossdehydrogenativecoup1ingofthio1swithP(O)Hcompounds;151(4)themu1ticomponentcoup1ingofary1boronicacids,diary1iodonium,orarenediazoniumsa1tswithe1ementa1su1fur(Ss)andP(O)Hcompounds;(5)thephosphorothio1ationofa1ky1ha1ides,ary1boronicacids,orarenediazoniumsa1tswithnewphosphorothio1ationreagents(suchasphosphorothioicacidsandphosphorothio1atesa1ts);171(6)thephosphorothio1ationofthio1sordisu1fideswithe1ementa1phosphorus.181A1thoughsignificantprogresshasbeenestab1ishedinphosphorothio1ationfie1d,therearesti11encountercha11engesinintroducingotherfunctiona1izationsorinvo1vingCyc1i1ationprocessesa1ongwithphosphorothio1ation(Scheme1b).Indeed,intermsofmu1tifunctiona1izationsinvo1vingphosphorothio1ation,thereareon1ytwocasesoff1uoroa1kyIphosphorothio1ationofa1kenes(CCsing1ebondswereformed)describedbyZhangeta1.191andonecaseofaminophosphorothio1a1ionofa1kenes(C=Cdoub1ebondswereretained)describedbyWueta1.1101However,tothebestofourknow1edge,thereexistsnoreportonphosphorothio1ationofa1kenesinvo1vingCyc1i1ationprocesses.Chromones,especia11y3-functiona1izedchromones,haverecent1yreceivedconsiderab1eattentionastheypossessmanyphysio1ogica1andbio1ogica1activities."11(a)Genera1methordsforthesynthesisofphosphorothoates:OO-CQ1Micae1s<ArtjzovtypereactionCaIR-SY.H-P<orU=R-S-Po°Y.SR102C1,etc.0r'0rOoHCa1condensationreact>z,rfc1R-SH.X-PT-r-s-p-OR0R,xOR,S801R-ZorNH4SCNPhosphorothio1ation5aOr-s-por,OR,inorganicsu1fursourceZH.B(OH)2.Br,N2BF4.etc.9OR1Phosphorotbio1ationvianewposph<xothMatonreagentsQoriR-SPorR-ZYS-FvOROR'OR,ZB(OH)2,Br.OH,etc;Y=H,N,Me2.MPhtha1imide.R-SHPhosphory1abonfromP4OR-S-RTsrSRCcfP4R-SS-RX=,Br921S-Hphoephorytetion°r,oR-SH.H-Pu-R-S-P<OR1OR1(b)Phosphoro1hioiationofa1kenesinvo1vingdfurct>onahzation(cha11enge)Phosphorothio1ation/difunctiona1izationthreeexamp1es1aOO÷HS-k0tOEt2aq了费EntrySo1ventI(eq.)T(eC)t(h)Yie1d(%)1MeCNh(1.0)604912MeCNI2O5(1.O)608473MeCNNIS(1.0)608654MeCNNaI(1O)608n.d.c)5MeCNTBAI(1O)608n.d.c6MeCNNH4I(1O)608trace7DCMI2(1O)608238THFh(1.0)608139DMSOh(1.0)608trace10DMFh(1.0)608trace11To1ueneb(1.0)608trace12NMPh(1.0)608trace13MeCNh(0.5)6046514MeCNh(2.0)6047815jMeCN1(1.0)60482MeCNI2(1O)6048717MeCNI2(1O)4046718MeCNI2(1O)8048619MeCN一604n.dc,a1Reactionconditions:1a(0.5mmo1),2a(1.0mmo1)in2m1ofso1vent.,b1Iso1atedyie1ds,1c,notdetected,1d11.0equiv.of(EtO)2P(O)SH.1e'3.0equiv.of(EtO)2P(O)SH.(c)Pbosphoro1hioiationZcyc1izationofOhydroxyarytenaminones