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Pd 催化的偶联反应. 经典 有机 合成反应 讲座 ( 五 ). 化学合成部执行主任 : 马汝建. 药明康德新药开发有限公司. 药明康德版权所有. 内容简介. Pd 催化的偶联反应有较多类型,目前用途最广泛的主要有以下三类 :. 1. Suzuki 反应 2. Heck 反应 3. Sonogashira 反应. 第一部分: Suzuki 反应. 1. 前 言. 1.1 Suzuki 反应的通式. 在钯催化下,有机硼化合物与有机卤素化合物进行的偶联反应,称之为 Suzuki 偶联反应,或 Suzuki-Miyaura 偶联反应。. 1. 前 言. - PowerPoint PPT Presentation
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Pd () :
1. Suzuki 2. Heck 3. Sonogashira
Pd :
Suzuki
1. SuzukiSuzuki-Miyaura 1.1 Suzuki
1. Suzuki Pd(0)-Pd(II) Pd(II)-Pd(0) 1.2 Suzuki
1. 1.3 Suzuki1.2.3.Suzuki 1. 2. Suzuki3. Suzuki
2. (), ()()2.1
2. Grinard
2. , 1995Ishiyama: (yield: 60-98%), -2.2
2. 1. DMSO DMF > dioxane > toluene 2. KOAcK3PO4K2CO33. Pd(dppf)Cl24. 2001Ishiyama Pd(dba)2/2.4PCy3(3-6mol %)
2.
2. 2.3 2.4
3. Suzuki1. Suzuki-couplingPd(0)-Pd(II) I > TfO > Br >> Cl2. -Pd(II)-arylaryl > alkylaryl > n-propyln-propyl > ethylethyl > methylmethyl3. SuzukiPd(PPh3)4PdCl2PdCl2(dppf)Pd(OAc)2Pd(PPh3)2Cl2NiCl2(dppf)
3. SuzukiSuzuki K2CO3K3PO4Na2CO3CsFCs2CO3t-BuONa,NaHCO3toluene/EtOH/H2O, CH3CN /H2Odioxane/H2O3.1 Suzuki
3. Suzuki SuzukiSuzuki, , NaOHBa(OH)2, DME2,4,6-: Ba(OH)2> NaOH > K3PO4 > Na2CO3 > NaHCO3, 3.2 Suzuki
3. Suzuki
3. Suzuki2-2-Na2CO3DME80, 39%. : , K3PO4, DMF, 89%Suzuki 3.3 Suzuki
3. SuzukiSuzuki Suzuki
3. SuzukiSuzuki 3-,3.4 Suzuki
3. Suzuki()Suzuki, TlOHTl2CO3, Suzuki, , , Suzuki3.5 Suzuki
3. Suzuki3.6 Suzuki
3. Suzuki3.7 TriflateSuzuki , PPh3Triflate, LiBrKBr
3. SuzukiMitchelldppbSuzuki98%; Wang Shen(PCy3)Pd(PCy3)Cl2 3.8 Suzuki
3. SuzukiSyun Satio,80NiCl2(dppf) (10 mol%)n-BuLi(40 mol%). NiCl2(PPh3)280% 3.9 Suzuki
3. Suzuki3.10 PdCl2Pd(OAc)2Pd/CHiroaPd/C Suzuki
3. SuzukiD. S. EnnisPd /C Suzuki-couplingSB-245570Pd(OAc)2Suzuki
Heck
1. Heck Heck2060Heck Morizoki,,C-CHeckTrans
2. Heck Heck
1Oxidative addition: RX (RX=I > TfO > Br >> Cl)Pd0L2Pd
2 Cordination-insertion:Pd-R 3-H
4Pd0L2
3. Heck Heck 1972Mori Ban1977HeckHeck
4. Heck DanishefskyTaxol4.1
4. Heck 2080Heck1989Shibasaki Overman HeckOvermanHeck 4.2
physostigmineHeck4.Heck
4. Heck Zeigler HeckHeckOverman Heck4.3
5. Heck Heck SP3SP3
5.1 Heck
5. HeckPd-HCurtin-HammettR CN,Wittig-Horner
5. Heck 1992Tamio HayashiHeck5.2Heck
, 18-N,N-1a96%ee 26-1a69%ee5.Heck
5. Heck5.3 Heck 5.3.1 BellerHeck
5. Heck
5.3.2 HeckHeck
5. Heck
5.3.3 Heck0.005 mol%
5. Heck
5.3.4 Heck20
Sonogashira
1. Sonogashira Sonogashira,
2. SonogashiraSonogashira(II)(CuI)
2. SonogashiraSonogashiraSonogashira
3. Sonogashira 1. 2. 3. 4.
Sonogashira
3.1 Pd(OAC)2PPh3CuINHCDMF
LiSonogashiraDABCO,Sonogashira,0.0001 mol%7200003.1
3.2 Elangovan2Sonogashira 3.2.1 (CuI)
Pd(OAc)2, Pd2(dba)3, PdCl2(dppf), PdCl2(PPh3)2, PdCl2(PCy)2, PdCl2, PdCl2(CH3CN)2Cs2CO3, Bu4NOAc, TBAF, Pyrrolidine, TEA, DBACO 3.2 3.2.2
3.3
3.3
3.3 3.3.1
3.3.2 3.3
3.3.3 3.3
3.3.4 3.3
3.4 SonogashiraHopkinsSonogashira Sonogashira
McLaughlinSonogashira3.4 LuSonogashiraCacchi
3.4 ,-
, 3.4
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