固相有机合成中钯催化的交叉偶联反应研究进展

:20111108;:20101206;:(1984-),,,;*,Email:[e-mail].专论郝树林1,2,张政朴1*,刘长令2(1南开大学高分子化学研究所,吸附分离功能高分子材料教育部重点实验室,天津300071;2沈阳化工研究院有限公司,新农药创制与开发国家重点实验室,沈阳110021):,CC,CC,HeckNegishiSuzukiStille,HeckNegishiSuzukiStille,:;;Heck;Negishi;Suzuki;Stille;引言2010DelawareRichardFHeckPurdueEiichiNegishi()HokkaidoAkiraSuzuki()Heck(1972)Negishi(1977)Suzuki(1979)33,(SolidPhaseOrganicSynthesis,SPOS)SPOS1963,R.B.Merrified[1],1984SPOS[2]SPOS,,,,SPOS11在聚合物载体上进行的Heck反应HeckPd(OAc)2Pd2(dba)3,CC,Heck11HeckHeckSPOS[4]SPOSHeck171[3]Figure1Typesoffunctionalisedpolystyreneresinsusedforpalladiumcatalysedandmediatedreactionsonsolidsupports(forreviewsandexplanations,seeRef.[3])Heck[Pd(OAc)2,PPh3P(oTol)3,DMF,80~100,2~24h][4]JefferyHeck[Pd(OAc)2,PPh3,Bu4NCl,K2CO3,DMF,20~80][5]Jeffery10%,Pd2(dba)3Pd(OAc)2[6]SPOSHeck()(1)(2),[7]12HeckHeck1995(21)2024(22)(2)[21],oCtrityl(3.1)20(32)(3)[22],15,[23]2201171HeckTable1IntermolecularHeckreactionsonsolidsupports:polymerboundaryliodidesandrelatedcompounds1Cleav:HCl,HTF,ultrasound,50,5minorHSiCl3,DCM,32,10minPd(OAc)2,PPh3,Et3N,DMF,ultrasound,80,24h8,92Cleav:(1)Et3O+BF-4;(2)PhB(OH)3,PdCl2(dppf),K2CO3,THF,60,14hPd(OAc)2,PPh3,K2CO3,DMF,70,14h103alkeneaR1=CO2tBu,R2=R3(69%)bR1=SO2Me,R2=R3(43%)cR1=Ph,R2=R3=H(NA)dR1=R3=H,R2=Ph(NA)eR1=R2=H,R3=Ph(NA)MeONa(6equiv),MeOH/dioxane(v/v14),24hAcONa,nBu4NCl,Pd(OAc)2,DMA,100,24h114Cleav:THF/DCM/PhOMe(50473)Pd(AcO)2,PPh3,Bu3NCl,sat.K2CO3,DMF/H2O(91),37,4h125Pd2(dba)3,Et3N,DMF,60,18h(DMFvolume:2~1mL/gofresin)136Pd(OAc)2,P(otol)3,Et3N,DMF/oxylene,MW,100147Pd(OAc)2,PPh3,Et3N,DMF15378Pd(OAc)2,Bu4NCl,NaOAc,DMA,100162HeckTable2IntermolecularHeckreactionsonsolidsupport:polymerboundalkenes1RX=Phl2naphthylBr,2thienylBr,3PyrBrPd2(dba)3,P(otol)3,Et3N,DMF,100,20horPd(OAc)2,Et3N,nBuNCl,DMF,80~90,16h172Arl;Ar=pTol,pBuC6H4,pMeOC6H4Pd(OAc)2,NaHCO3,DMF,145,20h183ArX;Ar=Ph,oH2NC6H4,oHOC6H4Pd2(dba)3,P(otol)3,Et3N,DMF,40~100,20h194Pd2(dba)3,P(tBu)3,DIPEA,supervriticalCO2(880psi),80,16h202Heck[21]Figure2IntramolecularHeckreactionforthesynthesisofmacrocycles[21],567,4201173Heck[22]Figure3IntramolecularHeckreactionforthesynthesisofamacrocycle[22],(3)3Table3Synthesisofindoles,benzofurans,dihydroisoquinolinesandbenzazepinesbyHeckreactionsonsolidsupports1Pd2(dba)3,CHCl3,P(oTol)3,NaHCO3,DMF,40,20h242Pd2(OAc)2,PPh3,Ag2CO3,DMF,100,16h253Pd2(OAc)2,PPh3,Bu4NCl,K2CO3,DMF,100,24h264Pd2(OAc)2,PPh3,Bu4NCl,K2CO3,DMF,100,24h26575Pd2(OAc)2,PPh3,Bu4NCl,K2CO3,70,24h2713HeckHeckWang(42)(43)Rink(41)44(4)[28]Heck,Heck70%~95%,44,41,5[28]Figure4Couplingofasolidsupportedpiperidinewith1,5hexadieneandarylhalides[28]2聚合物载体上的Negishi反应NegishiSPOSNegishi()(4),51[29](5)6163(6)[30],526471,[31]8283(8)[32]5[29]Figure5Arylarylcrosscouplingreactionwithpolymerboundarylbromides[29]6201176[30]Figure6Arylarylcrosscouplingreactionwithpolymerboundaryliodidesandtriflates[30]7[31]Figure7Arylarylcrosscouplingreactionwithpolymerboundarylzineates[31]8[32]Figure8Arylationofapolymerboundimidacylzincate[32]3聚合物载体上Suzuki偶联反应Suzuki()[38],,(),,Suzuki919BBN92(9),[39],,(5,1617)[51]774NegishiTable4Negishireactionswithimmobilisedzincsaltorwithimmobilisedarylhalidesandtriflates1(Hel)ArX=Phl,2BrPy,PhBRPPh3,DMF,reflux,18h332ArZnXAr=Ph,3MeOC6H4Pd2(dba)3,tBu3P.HBF4MW,THF/NMP175,10min343Ni(PPh3)2Cl2,PPh3,LiCl,THF,reflux,48h354Pd(PPh3)4,dryTHF,N2,rt,24h365RZnX(5eq)R=Ph,Ar,Bn,Alkyl(PPh3)4,THF,65,18h379[39]Figure9Derivatisationofaborane[39],Pd(OAc)2(03eq)PPh3(09eq)NaOH(3eq)(TritonB,15eq)(4eq)DMF8514hPdCl2(dppf)K2CO3(4min,40W)[60](5,67),Suzuki(5,25)8201175SuzukiTable5Suzukireactionswithimmobilisedaryloralkenylhalidesandtriflates/1RB(OH)2K2CO3,Pd(OAc)2,dioxane,H2O100,20h112ArB(OH)2PdCl2(dppf)Et3N,DMF,65,24h403Pd(PPh3)4K2CO3,DMF,70414ArB(OH)2Pd(PPh3)4K2PO4,DMF,80,24h425ArB(OH)2Pd(PPh3)4Na2CO3,tol/EtOH(81),90,24h426Pd(0),KOAc,DMSO,80,2h437PdCl2(dppf),KOAc,DMF,80,16h44978Pd(PPh3)4K3PO4,THF/H2O(61),80,2d459Pd(PPh3)4K3PO4,THF/H2O(61),80,2d4510Pd(PPh3)4K3PO4,THF/H2O(61),80,2d4511ArB(OH)2Pd(PPh3)42MNa2CO3,Xylene/H2O(61),80,24h4612RB(OH)2Pd(PPh3)4K3PO4,554713ArB(OH)2Pd(dppf)Cl2,K3PO4,toluene/tBuOH/H2O991,85,4h48102011714RB(OH)2cat,Pd(OAc)2,PPh3CsF,DME,4h,904915Pd(PPh3)4,Na2CO3,DMF/H2O(90/10),80,16h5016Pd(PPh3)4,Na2CO3,DMF,75,48h5117Pd(PPh3)4,K3PO4,DMF,75,48h5118PhB(OH)2Pd(PPh3)4,Na2CO3,DMF,75,48h5219ArB(OH)2;Ar=Ph,oMeC6H4,pF3CC6H4Pd(PPh3)4,Na2CO3,DMF/H2O151,80,45h5320Pd(PPh3)4,P(tBu)3,Cs2CO3,DMF,80,4h5421ArB(OH)2;Ar=pOHCC6H4,mO2NC6H4,mNHAcC6H4,pHO2CC6H4,pNCC6H4,m(F3C)2C6H3,3ThienylPd(OAc)2,dppf,Cs2CO3,DMF,90,16h55117221)ArB(OH)2:Ar=pOHCC6H4,mO2NC6H4,mNHAcC6H4,pHO2CC6H4,pNCC6H4,m(F3C)2C6H3,3Thienyl2)ethylchlorooximidoacetate,NEt3,THF,1h,fourtimesPd(OAc)2,dppf,Cs2CO3,DMF,90,16h5523ArB(OH)2:Ar=phenyl,mO2NC6H4,mMeOC6H4,pFC6H4,pMeOC6H4,pMeSC6H4,mEtOC6H4,3ThienylPd(PPh3)4,Na2CO3,Xylene/EtOH,80,24h5624PhB(OH)2PbCl2(PPh3)2,Cul,K2CO3DMF,reflux,18h3325Pd(dppf),K2CO3,THF/H2O,reflux,48h3526Na2CO3,Pd(PPh3)4,dioxane,reflux,48h3627pMeC6H4B(OH)2Pb(PPh3)4,K2CO3,toluene,EtOH,90,20h5728K2CO3,Pd(AcO)2,dioxane:H2O(61),110,21~48h58122011729PbCl2(PPh3)2,Na2CO3,H2O1530R2B(OH)2R2=4chloro2