第9章 鈀催化C-C鍵交叉偶聯(lián)反應(yīng)的機(jī)理

1、耙催化cc鍵交叉偶聯(lián)反應(yīng)及其機(jī)理+mXm=B(Suzuki-Miyaura)Sn(Stille)Zn(Negishi)Si(Hiyama).M=Fe,Rh,Ni,Pd.X=l,Br,Cl,OTf.Acc.Chem.Res.2013,46,2626-2634.1.鋰催化cc鍵交叉偶聯(lián)反應(yīng)AlfredNobelorCross-CouplingProductHalide3rdWaveVlbe卜sa如jwiOTh?NohelIviundAtkQTheNobelFcmrdUkvnHeckNegishiSuzukiLigand3rdWaveMetalCatalyst1stWaveCouplingPartn

2、er2ndWaveNanjingUniversityofScienceandTechnology7000-6000-5000-4W0-3000Suzuki HeckKumadaNegishiSonogashiraStille Buchwald-HartwigHlyamaAlphaketonearylation1000-0Pre19711fl71-1flfifl1fi81-1RftO20007001-2010Angew.Chem.Int.Ed.201乙51,5062-5085.NanjingUniversrtjiofScienceandTechnology19001910CuGteser18$9

3、：Ullman1901NO2XCu(3.7equiv)200°C.neatUllmann1901PdHalide3rdWaveR2-YCouplingPartner2ndWave19401950MeerweinlOkJ)KhdrasiclZnCIOCl76%(X二Br)+Me4SnTMetafCatalystfstWaveBrftBuHwLigandCross-Coupling1960廣丫I廣5丫Pd(OAc)2(1.0mol%)Pd(allyl)CI2(2.5mol%)19001910的ZRi=AlkylUylHartwl»1995R2=Alkyl.ArylrAlkyny

4、liHPBuchwaId19951920193(1194Q195019601970Cul(1mol%)HrPrffPPhoLUImcl%'PdCI2P(otoly1)32(5mol%)HMDS,toluene.100°C2ndWavePdChlPCo-tolyl)(2mol%)NaOfBu,toluene,100986%19701990PdCMPPhh(5mol%)/BnaAIHfIQmol%)；HartwEg199SPhCH2Pd(PPh3)2CI(0.05mol%)PdC以PPhJ(0.5mol%)PhDenmark1999I用ura19934SuchwaId199?2.

5、反應(yīng)機(jī)理LBP%1氧化加成2轉(zhuǎn)移金屬化3還原消除存在問(wèn)題：1缺乏更為具體深入的理論和驗(yàn)證研究。2對(duì)于具體的因素和條件對(duì)于反應(yīng)的影響缺乏明確和系統(tǒng)解釋和依據(jù)，如配體、金屬和底物的類型對(duì)于反應(yīng)的影響。2.1氧化加成LnpdLnPdXRPdLnSn2機(jī)理：1構(gòu)型反轉(zhuǎn)2液相反應(yīng)協(xié)同機(jī)理：1構(gòu)型保持2氣相反應(yīng)3某些極性溶劑NanjingUniversrtjiofScienceandTechnologyLnPd+(3KDOxidativeAdditionReductiveEliminationBrPd/LupR1LUP=UnhinderedPhosphineLHP=HinderedPhosphineR1B

6、(OH)2Pd/Sp91位阻小的磷配體，按SQ機(jī)理進(jìn)行，在烷基位置反應(yīng)。2位阻大的磷配體，按協(xié)同機(jī)理進(jìn)行，在芳基位置反應(yīng)。Chem.Eur.J.2010,16f13390-13397.NanjingUniversrtjiofScienceandTechnology22轉(zhuǎn)移金屬化TransmetalationA+m-(x)Suzukicouplings+X-B(OH)2R1-Pd-X+R2-B(OH)2R1-Pd-X+R2B(OH)Ppathway府pathway0)b(oh)3+x°aR1Pd卜R?HO°PathwayB)1 Pathway0.沒(méi)有堿反應(yīng)不能進(jìn)行。2 Pat

7、hwayA.主要的反應(yīng)途徑，堿首先活化硼酸。3 PathwayR與丹仍于競(jìng)爭(zhēng)反應(yīng)，堿*1%i/1Cm1,xoR1-Pd-OH+R2-B(OH)2+X0B(OH)3Stillecouplings(RX+-SnR3曬十(gg)+x-SnR3L-Pd-LIX+R2SnR3CyclicMecbanjsfn)L-Pd-R2R1XSnR3cis1環(huán)合機(jī)理A:鋰過(guò)渡態(tài)上只有一個(gè)配體配位B:有利于配體離去的特性（大位阻的磷配體）C:環(huán)合步驟為決速步（F取代CI降低能壘，Au降低環(huán)合過(guò)渡態(tài)的位阻）Y=LorsolventQpenMechanisrriR2SnR3XSnRsR1L-Pd-LR2trans2線性機(jī)理

8、A:鋰過(guò)渡態(tài)上有兩個(gè)配體配位B:有利于X基團(tuán)離去的特征（極性溶劑、三氟磺酸基）C:錫試劑取代X基團(tuán)是最高能壘ORLPdR2ILcisMe-Pd-CIZnMeCiIZnMeCIPdL2+Me-MecisLtransNegishicouplings咬X+-ZnY_+X-ZnY(Y=R2orhalide)1反式(trans)過(guò)渡態(tài)比順式(cis)的更容易生成2兩者是相互競(jìng)爭(zhēng)的反應(yīng)3只有順式過(guò)渡態(tài)可以轉(zhuǎn)化為最終產(chǎn)物4順?lè)词讲粫?huì)直接相互轉(zhuǎn)換NanjingUniversrtjiofScienceandTechnologySonogashiracouplings&x+H=Base()>r+H_

9、Basx°R1=aryl,hetaryl,alkenyl,alkyl,SiR$R2=aryl,hetaryl,vinylX=I,Br,Cl,OTfPdL2+R1-X+1Cu(l)可以活化烘婭生成烘基銅Cationic/RPX*AnionicMechanismMechanism2根據(jù)脫質(zhì)子和配體交換的順序，可以將機(jī)理分為陽(yáng)離子型機(jī)理和陰離子型機(jī)理。LR1-Pd-LHt-R2R1PdX3離子型機(jī)理與前兩種機(jī)理存在競(jìng)爭(zhēng)關(guān)系，可以有效提高反應(yīng)速率。4離子型機(jī)理中堿有兩個(gè)作用:結(jié)合質(zhì)子和鹵素(吸電基有利于反應(yīng)進(jìn)行)BaseH-Base5BaseH-R2L=”aRJd-LH-Bas/X0IIOXR2(/o門jcMechanism)R21轉(zhuǎn)移金厲化過(guò)程是反應(yīng)的決速步2鋰不與氫原子直接作用，堿與質(zhì)子結(jié)合后形成卡賓可以與鋰結(jié)合形成穩(wěn)定的環(huán)狀過(guò)渡態(tài)3Concertedmetalationdeprotonation(CMD)IS2.3還原消除ReductiveEliminationtransPdLn+1只有順式產(chǎn)物會(huì)進(jìn)行還原消除2還原消除過(guò)程不可逆3過(guò)渡態(tài)能壘大小：vinyl<Ph<ethynyl<Me,馬來(lái)酰胺v“empty*'vethylene<PMe3=