经典合成反应标准操作—钯催化的插羰反应
OPrBrPrCO,Pd(Ph3P)4(TiCl4,Mg,N2)K2CO3, 70%NHOMg2Cl2OTiNCO,THF+COPd(Ph3P)4, K2CO3NMP, 100oC, 1 atm, 87%OOPr
OPhI+CO+OOPhPdCl2(Ph3P)2Et3N, 56%OOOPhOO
如果在适当的位置有双键存在，那么在CO插入完成之后会紧接着发生烯键插入反应。在化合物8-3的分子内反应中，通过使用不同的催化剂可以得到不同的产物：使用Pd(dba)2作催化剂，插羰后得到产物8-4；而使用PdCl2(Ph3)2作催化剂则得到化合物8-5。
OPd(dba)2, Et3NMeCN, 93%I+COO8-3PdCl2(Ph3P)2Et3N, MeOH, 84%O8-5O8-4OCO2Me
下面是通过芳基卤化物与分子内双键的羰基化反应合成杂环化合物8-6的实例：
BrNHOO+COPd(OAc)2, Ph3P, K2CO3 DMF, 120oC, 12 atm., 87%O8-6OOO
Page 25 of 31
经典合成反应标准操作—钯催化的插羰反应
邻碘苯酚与降冰片二烯和CO反应得到内酯8-7，它可以通过反Diels-Alder反应进一步转化成香豆素8-8。
I+OH+COPd(Ph3)4, anisole1 atm, 80oC, 90%O8-7150oC+O8-8OO
有末端炔烃和非末端炔烃参与的卤化物羰基化反应可以得到各种各样的产物。取代二氢茚酮8-9的合成就是通过在Pd(Ph3P)4和Zn催化下邻二碘苯和炔烃、CO反应制得的。
OI+IEtEt+COPd(Ph3P)4, ZnEtOH, 63%Et8-9Et
在末端炔烃存在情况下，芳基碘化物的羰基化反应可以制备酰基炔烃8-10。在这个反应中，使用双齿配体（如dppf）可以得到非常好的结果。但如果使用Ph3P作为配体，苯乙炔主要转化成二苯乙炔。
Ph-I+CO+PhPdCl2(dppf), Et3N20 atm., 120oC, 86%PhCO8-10Ph
通过类似的反应，三氟甲磺酸酯8-11可以生成炔酮8-12：
OPh+CO+TfO8-11PhPd(OAc)2, dppe, Et3NDMF, 1 atm., 75%Ph8-12Ph
Page 26 of 31
经典合成反应标准操作—钯催化的插羰反应
用Zn-Cu试剂作为还原剂，通过Pd和Cp2TiCl2协同催化下，烯酮8-13能够以较高收率被制备：
Ph-I+CO+BuPdCl2(Ph3P)2, Cp2TiCl2Zn/Cu, 1 atm., 92%Ph8-13OBu
通过卤化物与炔烃的羰基化应制得的炔基酮可以和自身具有的亲和试剂进一步发生分子内反应：
I+CO2MePh+COPd(Ph3P)4, AcOK80oC, 1 atm., 74%CO2MeOPd(II)PhPhOO
O
Pd(Ph3P)4,anisoleAcOK, 82%I+OHPdCl2(dppf)2, Et2NH120oC, 20 atm., 81%OPh
Ph+COOOPh
I+NH2Ph+COOPdCl2(Ph3P)2, Et2NH120oC, 20 atm., 81%NH2OPhNHPh
Page 27 of 31
经典合成反应标准操作—钯催化的插羰反应
OC3H7HNBr+CO2MePh+COPdCl2(dppf)40 atm., 86%PhNC3H7ONaHPhNC3H7CO2MeCO2Me
碘苯和苄基乙炔8-14通过羰基化反应得到(E)-3-arylidenebutenolide 8-16（也可以通过苯乙酰基炔的羰基化反应制备）。烯基钯化物8-15被形成通过Pd-H加成反应。接着烯醇形成，双键异构化，二次羰基化反应得到丁烯羟酸内酯8-16。
Ph-I+OMe8-14+COPd(OAc)2, Ph3PEt3N, 120oC, 55%OMeOMeOPhOMePhOHPd8-15HPhOO8-16
在10 atm下，CO和CO2混合气体中，碘苯和取代炔丙基醇8-17反应得到3(2H)-furanone 8-20。首先碘苯和醇8-17以及CO通过羰基化反应生成苯乙酰炔基醇8-18；然后CO2与醇8-18加成得到碳酸酯8-19；最后脱羧重排得到8-20。
Pd(Ph3P)4Pd-I+8-17OPhOHCO2OO8-188-198-20PhOPhOOH+CO+CO2Et3N, 100oC, 79%OO
Page 28 of 31
经典合成反应标准操作—钯催化的插羰反应
在KCN存在的条件下，碘苯会发生氰基羰基化反应，从而生成苯甲酰氰化物8-21。
I+CO+KCNPhPd(Ph3P)2I, THF20 atm., 100oC, 91%8-21COCN
9. 插羰反应制备酮实验操作
I+OSi(Et)F2+COO(η3-C3H5PdCl)2, KF1 atm, 100oC, DMIO
To a suspension of KF (190 mg, 3.3 mmol), (η3-C3H5PdCl)2 (18 mg, 2.5 mol%), and 1-(4-iodophenyl)ethanone (490 mg, 2.0 mmol) in DMI (10 mL) was added difluoro(ethyl)(4-methylphenyl)silane (560 mg, 3.0 mmol) under 1 atm of carbon monoxide (balloon). After stirring at roon temperature for 10 min, the reaction mixture was heated at 100oC for 3 hours. Bulk of the solvent and the catalyst were removed by passing the mixture through a silica gel column with ethyl acetate-hexane = 1:10 as an eluent solvent. Evaportation of the solvent under reduced pressure afforded 4-acetylphenyl-4-methylphenyl ketone as a colorless solid (430 mg, 91%).
Ph-I+CO+BuPdCl2(Ph3P)2, Cp2TiCl2Zn/Cu, 1 atm., 92%Ph8-13OBu
A mixture of PdCl2(PPh3)2 (14 g, 0.02 mol), Cp2TiCl2 (10 mg, 0.04 mol), and Zn-Cu (98 mg, 1.5 mmol) was purged with carbon monoxide (equipped with a CO balloon). Into this mixture was added a solution of an aryl iodide (1.0 mmol) in 2.5 mL of dry dimethoxyethane in a syringe. The heterogeneous reaction mixture was immersed into an oil bath maintained to 65 ℃ and stirred for 4 hours. After evaporation of the solvent, the reaction mixture was directly subject to column chromatography (silica gel) and product 8-13 (92 %) was isolated.
Page 29 of 31
经典合成反应标准操作—钯催化的插羰反应
I+CO+CO2EtCO2EtPd(0), dppfEt3N, 120oC, 75%OCO2EtCO2Et8-1
Iodobenzene (1.8 mmol) and diethyl methylmalonate (2.0 mmol) in triethyl amine (2 mL) were reacted with carbon monoxide (20 atm) at 120℃ in the presence of a catalytic amount of dichloro[1,1’-bis(diphenylphosphino)ferrocene]-palladium (1.88*10-2mmol). GLC analysis of the resulting mixture revealed the formation of diethyl methylbenzoylalonate in 75.3% yield. The mixture was filtered and distilled (Kugelrohr) to give the pure sample (61% isolated yield).
The End
Page 30 of 31