The Challenge of Palladium-Catalyzed Aromatic Azidocarbonylation: From Mechanistic and Catalyst Deactivation Studies to a Highly Efficient Process
The Challenge of Palladium-Catalyzed Aromatic Azidocarbonylation: From Mechanistic and Catalyst Deactivation Studies to a Highly Efficient Process
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DOI：
10.1021/om401126m
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发表时间：
2014-02-10
期刊：
影响因子：
2.8
通讯作者：
Grushin, Vladimir V.
中科院分区：
文献类型：
--
作者：
Miloserdov, Fedor M.;McMullin, Claire L.;Grushin, Vladimir V.
碘代芳烃与CO和NaN 3的叠氮羰基化反应是一种新型的Heck型羰基化反应，在室温和1个大气压下，在有机溶剂-水两相体系中容易发生，生成芳酰叠氮化合物。该反应是由Xantali-Pd催化的，并表现出高的官能团耐受性。催化剂失活产物[（Xantphos）PdI 2]可以原位还原。用PMHS转化为Pd（0）以恢复催化活性。以这种方式，催化剂负载量已降低至0.2%，在几乎100%转化率下没有任何选择性损失，以克规模以80-90%的分离产率合成一系列芳酰基叠氮化物。或者，ArCON 3产物可不经分离用于进一步原位转化，例如，异氰酸酯、脲、苯甲酰胺和亚氨基磷烷。详细的实验和计算研究已经确定了两个主要的反应途径的反应。对于这两种途径，Ar-I与Pd（0）的氧化加成是速率决定步骤。在过量CO存在下，Ar-I键被混合羰基膦络合物的较少富电子的Pd中心活化。在CO缺乏的条件下，一个稍低的能量势垒途径，涉及Ar-I氧化加成到一个更具反应性的羰基自由（Xantphos）Pd-0物种。用于反应的三相液液气体系中的传质在这两个反应通道之间的竞争中起着重要作用，均匀地导致共同的芳酰基叠氮基中间体经历非常容易的ArCO-N-3还原消除。已对该方法的安全性进行了研究。
Azidocarbonylation of iodoarenes with CO and NaN3, a novel Heck-type carbonylation reaction, readily occurs in an organic solvent-H2O biphasic system to furnish aroyl azides at room temperature and 1 atm. The reaction is catalyzed by Xantphos-Pd and exhibits high functional group tolerance. The catalyst deactivation product, [(Xantphos)PdI2], can be reduced in situ. with PMHS to Pd(0) to regain catalytic activity. In this way, the catalyst loading has been lowered to 0.2% without any losses in selectivity at nearly 100% conversion to synthesize a series of aroyl azides in 80-90% isolated yield on a gram scale. Alternatively, the ArCON3 product can be used without isolation for further transformations in situ, e.g., to isocyanates, ureas, benzamides, and iminophosphoranes. A detailed experimental and computational study has identified two main reaction pathways for the reaction. For both routes, Ar-I oxidative addition to Pd(0) is the rate-determining step. In the presence of CO in excess, the Ar-I bond is activated by the less electron-rich Pd center of a mixed carbonyl phosphine complex. Under CO-deficient conditions, a slightly lower energy barrier pathway is followed that involves Ar-I oxidative addition to a more reactive carbonyl-free (Xantphos)Pd-0 species. Mass transfer in the triphasic liquid liquid gas system employed for the reaction plays an important role in the competition between these two reaction channels, uniformly leading to a common aroyl azido intermediate that undergoes exceedingly facile ArCO-N-3 reductive elimination. Safety aspects of the method have been investigated.