经典合成反应标准操作—钯催化的插羰反应
7. 插羰反应制备醛实验操作
Br+NCO+H2PdBr2(Ph3P)2, benzene Et3N, 1200 Psi, 145oC, 80%NCHO
To the 45 mL-Parr bombwere added 3.95 g (25.0 mmol) of 3-bromopyridine, 10 mL of triethylamine,
10
mL
of
benzene,
and
0.30
g
(0.375
mmol)
of
dibromobis(triphenylphosphine)palladium (II). The bomb was then flushed with argon, sealed, and pressurized to 600 Psi with carbon monoxide. After the pressure was released, the bomb was re-pressurized to 600 Psi with carbon monoxide and finally pressurized to 1200 Psi with hydrogen. The reaction vessel was heated in an oil bath with stirring at 145oC. After 20 min, the pressure reached a maximum of 1350 Psi. Times and pressure were periodically recorded until gas absorption stopped (26 hr), and the pressure in the reaction vessel had decreased to 1025 Psi. The reaction vessel was cooled, and the gases were slowly released. After addition of anhydrous ether, the reaction mixture was filtered to remove the triethylamine hydrochloride, concentrated in vacuo to remove ether, benzene, and triethylamine, and finally distilled to give 2.15 g of (80% yield) of product.
Br+BrCO+H2PdBr2(Ph3P)2, tri-n-butylamine benzene, 1200 Psi, 145oC, 80%CHO CHO
The 75-mLreaction bomb was charged with 5.9 g (25.0 mmol) of 1,4-dibromobenzene, 11.2 g (60.0 mmol) of tri-n-butylamine, 15 mLof benzene, and 0.4 g (0.5 mmol) of dibromobis(triphenylphosphine)palladium (II). The bomb was then flushed with argon, sealed, and pressurized to 600 Psi with carbon monoxide. After the pressure was released, the bomb was re-pressurized to 600 Psi with carbon monoxide and finally pressurized to 1200 Psi with hydrogen. After 15 min, the pressure reached 1375 Psi at 140oC and decreased to 600 Psi after 24 hr of treaction. The vessel was then cooled to room temperature and the pressure released. After addition of anhydrous ether, the reaction mixture was filtered to remove the
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经典合成反应标准操作—钯催化的插羰反应
triethylamine hydrochloride, concentrated in vacuo to remove ether, benzene, and triethylamine. After evaporation of the ether, the resulting solids were sublimed (100oC, 8 mm) to give 3.79 g of a mixture of the terephthalaldehyde and 1,4-dibromobenzene. The mixture was separated by chromatography on silica gel. There were obtained 0.66 g (2.8 mmol) of 1,4-dibromobenzene and 2.47 g (18.4 mmol) of 1,4-benzenedicarboxaldehyde (83% yield). Recrystallization from hexane yielded 2.21 g of pure dialdehyde.
8. 插羰反应制备酮
在Zn, B, Al, Sn, Si, Hg等有机金属化合物或其他亲核试剂（他们可以进攻酰基钯中间体，发生金属转移和还原消去反应）的存在下，卤化物和类卤化物的羰基化反应可以生成酮。
芳基碘化物在烷基碘化物和Zn-Cu存在条件下发生插羰反应，以非常高的收率生成了烷基芳基酮。这个反应首先生成烷基锌试剂，然后再发生金属转移和还原消去反应。
Ph-I+COPd(Ph3P)41 atm.Ph-COPd-IZnI93%PhO+ZnCl2I+Zn-Cu
在碱性条件下，有机硼化物可以被用于合成酮的插羰反应中：
Ph-I+CO+Et3BPdCl2(Ph3P)2Zn(acac)2, HMPA, 82%PhMOMO+9-BBN+COIPdCl2(Ph3P)2K3PO4, PhH, 74%O
O
MOMO
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经典合成反应标准操作—钯催化的插羰反应
OB(OH)2+CO+PhCH2BrOMOMPdCl2(Ph3P)2, K2CO31 atm., 78%OPhOPhOMOM
9-C8H17-9-BBN+CO+C6H13IPd(Ph3P)4, K3PO4dioxane, 67èH17OC6H13
有机铝化物（例如三苯基铝）可以被用于合成酮的插羰反应。应注意的是，i-Bu3Al应用此类反应时，往往会发生还原羰基化反应，从而生成相应的醇：
OMePh3Al+I+COPdCl2(PhCN)2DMSO, 98%OMeO
PhI+CO+PdCl2(Ph3P)23PhOHAlDME, 95%
有机锡化物，如芳基、烯基和炔基锡化物，可以用于合成酮的插羰反应。反应机理和实例应用如下图所示：
Pd(0)Ar-I+COArCO-Pd-XBu3SnArCOPdArCO+Bu3SnX+Pd(0)
I+CO+Me4SnPhPd(Ph3P)2IHMPA, 120oC, 85%COCH3
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经典合成反应标准操作—钯催化的插羰反应
OTf+CO+Bu3SnSiMe3PdCl2(dppf)LiCl, 50~60%OOPdXOOSiMe3
N2BF4Pd(OAc)2, MeCN+CO+Me4SnCl9 atm., rt., 90%ClCOMe
OTf+TMs+COPd(Ph3P)4, LiClTHF, 1 atm., 86%TMSOMe3Sn
OPdCl2(MeCN)2DMF, LiCl, 53%OOOSnBu3+COOOTf
有机硅化物可以用于合成酮的插羰反应：
ISSiEt2F+CO+CHOπ-C3H5PdCl, KF, DMF100oC, 1 atm., 72%SOCHO
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经典合成反应标准操作—钯催化的插羰反应
OTfEtOOSiMe3++COPd(Ph3P)4HMPA, 87%OOCO2EtOOOPdCO2Et
烷基和芳基汞（II）的卤化物也可以用于酮的合成反应，因为此类反应并不多见，所以在此就不再列举。
如果用活性亚甲基化合物（例如β-酮酯或丙二酸酯）代替醇类化合物进行插羰反应，可以得到β-酮酯或丙二酸酯的衍生物8-1。对于这个反应来说，dppf是非常好的配体。通过烯醇式阴离子捕获酰基钯中间体的方式发生分子内反应，可以形成五元和六元环。化合物8-2的形成就是一个典型实例。这是一个非常有价值的反应。
I+CO+CO2EtCO2EtPd(0), dppfEt3N, 120oC, 75%OCO2EtCO2Et8-1
CO2MeICO2Me+COPd(Ph3P)4, 60 Psi100oC, Et3N, 90%O8-2CO2MeCO2Me
当有一个可烯醇化的羰基存在的时候，C和O之间的捕获竞争就会发生。一般来讲，在形成同样大小环的情况下，O的捕获能力要强于C的捕获能力，因此更多的情况下是形成内酯。
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