有機合成Class_No_4

1、第四章第四章 HeckHeck反應(yīng)反應(yīng)HRX+ Base Pd R+ Base -HXRPdXRXPd (0)RBaseRHPdXHHPdX+ Base - HXR - H elimination124 4. .1 1 分分子子間間 H He ec ck k 反反應(yīng)應(yīng)1. 插入反應(yīng)的區(qū)域選擇性HCO2CH3HH3CH2CCH3PhPhHHH3CPhHH3CHHHNOCH2 = CHCO2CH3CH2 = CHCNCH2 = CHPhCH2 = CHCH(OCH3)2CH2 = CH - CH - CH310010010096 110010093 779 218020100901040 60OH

2、 2. 立體選擇性MePhPhPhMePhBrEt3NPd(OAc)2PPh3E - isomerE - isomer70 %+MePhPhPhMePhBrEt3NPd(OAc)2PPh3Z - isomerZ - isomer79 %+HMeHPhPd+PhMeHPhHPd+HPhMePhHMePhHPhPd+ - PhE isomerSyn - additionrotationelimination3MeHHPhPd+PhHMePhHPd+HMePhPhHPhMeHPhPd+ - PhZ isomerSyn - additionrotationelimination43. 鹵代物的活潑性

3、零價鈀對鹵代物的氧化加成的難易程度，取決于碳鹵鍵的強弱。一般說來，碘化物比溴化物活潑，而氯化物則在一般情況下不反應(yīng)。對于芳基鹵化物，芳環(huán)若帶有吸電子基團，有利于氧化加成。 4. 反 應(yīng) 類 型( 1 ) 簡 單 烯 烴 的 反 應(yīng)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) 共軛雙鍵+RXPdBase-H eliminationNu-Nu+Nu6785RPdLnHHRHRR( 3 ) 烯 丙 醇IC6H13+OHC6H13OHC6H13CHOC6H13HaPdOHHbpath aPd(OAc)2, Ag2CO3Bu4NHSO4, CH3CN54%path bPd(OAc)2, PPh3AgOAcDMF, 61%91011(4) 鹵 代 烷 與 末 端 炔 的 偶 聯(lián)

5、 反 應(yīng)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) 聯(lián) 烯+RXPdPdLnNu-20CH2RRR-H elimination21RRNuRR22 4 4. . 2 2 分分子子內(nèi)內(nèi) H H e ec ck k 反反應(yīng)應(yīng)(1) 碳碳雙鍵(包括共軛雙烯)的 分子內(nèi) H eck 反應(yīng)XRnPd(0)PdXRnPdXnR232425(8) (2) 聯(lián) 烯 的 分 子 內(nèi) H

7、 eck 反 應(yīng)XnPd(0)RPdXnRnRPdX262728(9)(3) 碳碳叁鍵的分子內(nèi) H eck 反應(yīng)XRnPd(0)PdXRnPdXnR293031(10)4 4. .2 2. .1 1 以以 H H 消消 除除 終終 止止 的的 分分 子子 內(nèi)內(nèi) H H e ec ck k 反反 應(yīng)應(yīng)一一、芳芳基基、烯烯基基鹵鹵代代物物的的分分子子內(nèi)內(nèi) H H e ec ck k 反反應(yīng)應(yīng) 1 1、 成環(huán)大小的一般規(guī)律和影響因素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) 立體位阻對成環(huán)的影響PdIIPdIPdIHHPdILnPd(OAc)2PPh3CH3CNababK2CO3- H elimination- H eliminationno - H666768697068: 70 = 1:1.5(2) 電子效應(yīng)對成環(huán)的影響HOHIOC

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

11、nationR = H828384858687888990(4) 鹵 素 原 子 對 成 環(huán) 大 小 選 擇 性 的 控 制BrEEPd(OAc)2Ph3P, K2CO3CH3CN, 67%EEEE919495E = COOEtEEPdBrLnEE9392BrBrBrBrPdBrLn2 2 影影響響環(huán)環(huán)化化產(chǎn)產(chǎn)率率的的因因素素(1) 碳碳雙鍵取代基對分子內(nèi) H eck 反應(yīng)的影響B(tài)rHNRPhOHNPhROPd(OAc)2, P(o-tol)3100 oC, Et3NR = H 58%R = CH3 21%9697(16)NMeOBrONMeONMe+Pd(OAc)2Et3NPPh358%Ag

12、2CO39899100(17)(2 ) 電 子 效 應(yīng) 的 影 響B(tài)rOHNHOHOHOHNHOONHBrOAcNAcOAcOAcOAcNAcOAcOAcNAcAc2O(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、 分分子子內(nèi)內(nèi) H H e ec ck k 反反應(yīng)應(yīng)中中新新生生成成雙雙鍵鍵的的位位置置（ 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) 新生成雙鍵的異構(gòu)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. . 烯烯丙丙基基鹵鹵化化物物及及醋醋酸酸酯酯和和芐芐基基類類鹵鹵化化物物的的分分子子內(nèi)內(nèi)H H e ec ck k 反反應(yīng)應(yīng)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. . 聯(lián)聯(lián)烯烯的的分分子子內(nèi)內(nèi)碳碳鈀鈀化化反反應(yīng)應(yīng)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