经典合成反应标准操作—钯催化的插羰反应 药明康德新药开发有限公司
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.
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经典合成反应标准操作—钯催化的插羰反应 药明康德新药开发有限公司
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
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