有机合成Class_No._4

1、第四章第四章 HeckHeck反应反应HRX+ Base Pd R+ Base -HXRPdXRXPd (0)RBaseRHPdXHHPdX+ Base - HXR - H elimination124 4. .1 1 分分子子间间 H He ec ck k 反反应应1. 插入反应的区域选择性HCO2CH3HH3CH2CCH3PhPhHHH3CPhHH3CHHHNOCH2 = CHCO2CH3CH2 = CHCNCH2 = CHPhCH2 = CHCH(OCH3)2CH2 = CH - CH - CH310010010096 110010093 779 218020100901040 60OH

2、 2. 立体选择性MePhPhPhMePhBrEt3NPd(OAc)2PPh3E - isomerE - isomer70 %+MePhPhPhMePhBrEt3NPd(OAc)2PPh3Z - isomerZ - isomer79 %+HMeHPhPd+PhMeHPhHPd+HPhMePhHMePhHPhPd+ - PhE isomerSyn - additionrotationelimination3MeHHPhPd+PhHMePhHPd+HMePhPhHPhMeHPhPd+ - PhZ isomerSyn - additionrotationelimination43. 卤代物的活泼性

3、零价钯对卤代物的氧化加成的难易程度，取决于碳卤键的强弱。一般说来，碘化物比溴化物活泼，而氯化物则在一般情况下不反应。对于芳基卤化物，芳环若带有吸电子基团，有利于氧化加成。 4. 反 应 类 型( 1 ) 简 单 烯 烃 的 反 应HRX+cat. PdbaseRR = 1-alkenyl, allylic, benzyl, 1-alkynyl, arylX = OTf, Br, I, I+Ph, SO2Cl, COCl, etc.PhI+COOMecat. Pd(OAc)2, NaHCO3n-Bu4NCl, 30oC, 1 dCOOMePhPhI+COMecat. Pd(OAc)2, NaHC

4、O3n-Bu4NCl, 25oC, 2 dCOMePh94%98%IC4H9+COOMecat. Pd(OAc)2, NaHCO3n-Bu4NCl, 27oC, 4 hCOOMe96%C4H9 (2) 共轭双键+RXPdBase-H eliminationNu-Nu+Nu6785RPdLnHHRHRR( 3 ) 烯 丙 醇IC6H13+OHC6H13OHC6H13CHOC6H13HaPdOHHbpath aPd(OAc)2, Ag2CO3Bu4NHSO4, CH3CN54%path bPd(OAc)2, PPh3AgOAcDMF, 61%91011(4) 卤 代 烷 与 末 端 炔 的 偶 联

5、 反 应HCCRRCCR+RXBasecat. PdCl2(PPh3)2cat. CuI(3)(Ph3P)2PdCl2Et2NH2ClRCuI, Et2NH(Ph3P)2Pd(C=CR)2RR(Ph3P)2Pd(0)RX(Ph3P)2PdRXRCuI, Et2NHEt2NH2X(Ph3P)2PdRRRR121314ClR2HR1+R3PdCl2L2, CuINHR2HR1R3up to 97%(4)+RPdCl2(PPh3)2IHOCuIRHOR = aryl, CH2OH, alkyl(5)OTfOTf+R1L2PdCl2CuI, i-Pr2NHOTfR1R2R1R2151617(6)R1C

6、lNR2+R3L2PdCl2Et3N, CuIR1NR2R351-79%1819(7)BrR1R2R3+R5R42.5 mol% Pd(OAc)210 mol% PPh3Cs2CO3, DMF, 130 oCR1R2R3HR5R4Chem. Lett. 1997, 823.(5) 联 烯+RXPdPdLnNu-20CH2RRR-H elimination21RRNuRR22 4 4. . 2 2 分分子子内内 H H e ec ck k 反反应应(1) 碳碳双键(包括共轭双烯)的 分子内 H eck 反应XRnPd(0)PdXRnPdXnR232425(8) (2) 联 烯 的 分 子 内 H

7、 eck 反 应XnPd(0)RPdXnRnRPdX262728(9)(3) 碳碳叁键的分子内 H eck 反应XRnPd(0)PdXRnPdXnR293031(10)4 4. .2 2. .1 1 以以 H H 消消 除除 终终 止止 的的 分分 子子 内内 H H e ec ck k 反反 应应一一、芳芳基基、烯烯基基卤卤代代物物的的分分子子内内 H H e ec ck k 反反应应 1 1、 成环大小的一般规律和影响因素NOPhINOPhPdINOPhPdILnHNOPhNOPh(CH2)nNOPh(CH2)n(CH2)n(CH2)nban-Bu4NClPd(OAc)2Ph3PK2CO3

8、CH3CN(CH2)n(CH2)n- H elimination- H eliminationab323537333436LnIPdNIOPd(OAc)2n-Bu4NClPh3PK2CO3CH3CNNO3839(11)BrEEPd(OAc)2Ph3P, K2CO3CH3CN, 67%EE+EE404142E = COOEt5:4EEPdBrLnEEPdBrLnPdBrLnEE434445ZBrZZ = CH 47aZ = N 47b(12)Z = CH 46aZ = N 46bPd70-90%OHHBrOHHOHH+4849502:1(13)5% Pd(OAc)210% PPh380 , 23

9、h, 67%BrHNPdBrLnPdBrLnPdBrLnNPdBrLnNPdBrLnPd+HPdLnXHPdLnXNH5157 (4%)525354555658596061 (8%)Pd(OAc)2, P(OEt)3CH3CN, 125 , 12hPdIIPd(OAc)2PPh3CH3CNababexoexo62636465(1) 立体位阻对成环的影响PdIIPdIPdIHHPdILnPd(OAc)2PPh3CH3CNababK2CO3- H elimination- H eliminationno - H666768697068: 70 = 1:1.5(2) 电子效应对成环的影响HOHIOC

10、at. Pd(OAc)2K2CO3, n-Bu4NCl DMF 53%H717273(14)IEEEEE EEE( )12120 oC, 12 h2166%Pd(15)7475(3) H对 成 环 的 影 响BrRNOPdBrLnRNORNLnBrPdORNOPdBrLnRNORNOPd(OAc)2100 oCEt2O767778798081R = H; 52%; 85:88 = 9:1R = Me; 50% (88)NIORRRRNLnIPdORRRRNORRRRLnIPdNOORRRRNPdILnORRRRNORRRRNNORRRRPdILnNORRRRPd(0)abab- H elimi

11、nationR = H828384858687888990(4) 卤 素 原 子 对 成 环 大 小 选 择 性 的 控 制BrEEPd(OAc)2Ph3P, K2CO3CH3CN, 67%EEEE919495E = COOEtEEPdBrLnEE9392BrBrBrBrPdBrLn2 2 影影响响环环化化产产率率的的因因素素(1) 碳碳双键取代基对分子内 H eck 反应的影响BrHNRPhOHNPhROPd(OAc)2, P(o-tol)3100 oC, Et3NR = H 58%R = CH3 21%9697(16)NMeOBrONMeONMe+Pd(OAc)2Et3NPPh358%Ag

12、2CO39899100(17)(2 ) 电 子 效 应 的 影 响BrOHNHOHOHOHNHOONHBrOAcNAcOAcOAcOAcNAcOAcOAcNAcAc2O(63%)6% Pd(0)1. HPdX2. O89%36%1011021031041051062 x 2.5%Pd (0)NR2OR3R1R1R2INR2OR3R1R1R2Pd(OAc)2, PPh3n-Bu4NCl, K2CO3107108a: R1 = R2 = R3 = Hb: R1 = OMe, R2 = R3 = Hc: R1 = R2 = OMe, R3 = Hd: R1,R1 = OCH2O R2 = OMe,R

13、3 = Hyield (%)575138233 3、 分分子子内内 H H e ec ck k 反反应应中中新新生生成成双双键键的的位位置置（ 1 ） H 消除的方向I5% Pd(PPh3)4, NEt3CH3CN-THF, reflux6 h109110ICOOMeCOOMePdILnHHCOOMeH5% Pd(PPh3)4NEt3, 1.5 equivMeOH, THFreflux, 20 hCO2EtICO2EtHPdILnH3.0% Pd(OAc)29.0% PPh3CH3CN , Ag2CO380 oCCO2EtH42%111112113114115116(2) 新生成双键的异构化I

14、HNHNPdILnHNHNHNPdILnHHN2% Pd(OAc)2NEt3, 2.5 equiv.Et3N, Bu4NCl, DMFHPdXLn73%117118119120121122ICO2EtCO2EtCO2EtCO2EtCO2EtCO2EtPd(PPh3)4NEt3, MeCN, THFreflux82%126127(19)Br5% Pd(PPh3)4, NEt3CH3CN, reflux+68%17%1231241251 h0.5 h 82% 1%NCOOCH3IN-COOCH3N-COOCH3Pd(OAc)2PPh3, Et3Na: X = Ib: X = BrYield:82%

15、52%1 / 1.68 / 1+128129130(20)NCH3IONCH3O+double bondregioisomera: 1% Pd(OAc)2, 3% PPh3 2 equiv, Et3N, CH3CN, 3 hb: 1% Pd(OAc)2, 3% PPh3 2 equiv, Et3N, 3 h 1 equiv. AgNO31 : 126 : 1Yield: 70%131132(21)2 2. . 烯烯丙丙基基卤卤化化物物及及醋醋酸酸酯酯和和苄苄基基类类卤卤化化物物的的分分子子内内H H e ec ck k 反反应应ClEClEEEPd(PPh3)4NEt3(72%)(64%)5%

16、Pd(PPh3)4NEt3(1.5 equiv)CH3CN, reflux,6 h133134135136EEAcOEEAcOEEHE = COOEtPd(PPh3)4HOAc1 h, 84%Pd(PPh3)4HOAc4 h, 55%137139138NCOCF3AcONCOCF3NCOCF3Pd(PPh3)4HOAc59 - 76%+90 : 10140141142(22)3 3. . 联联烯烯的的分分子子内内碳碳钯钯化化反反应应Br.I69%Br.I66%.IEE.EEI58%.IEE.EEI56%8.BrEEEEII62%( )39Br.II48%( )610E / Z = 73 : 2

17、7I.II57%( )711I: 5% PdCl2(PPh3)2, K2CO3 (5 equiv), EtOH (10 equiv), DMF.II: 5% PdCl2(PPh3)2, K2CO3 (5 equiv), n-Bu4NCl (1 equiv), DMF.E = COOEtOOII100 oC, 2 h52%, 74% by NMROOII100 oC, 21 h 5% by NMRBrII120 oC, 12 h55%( )29( )5BrII120 oC, 12 h 2%( )29( )5( )5+dimer, trimer, etc10 2%IEEEEEEEEII80 oC, 29 h( )41250%IEEEEE EEEHEEEEII80 oC, 35 h( )418%( )4+37%13IEEEEEEEEII120 oC, 5h( )122086%IEEEEEEEEE EEE( )12II120 oC, 12