Alkyl Isocyanates via Manganese-Catalyzed C-H Activation for the Preparation of Substituted Ureas
Alkyl Isocyanates via Manganese-Catalyzed C-H Activation for the Preparation of Substituted Ureas
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DOI：
10.1021/jacs.7b07658
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发表时间：
2017-11-01
影响因子：
15
通讯作者：
Groves, John T.
中科院分区：
文献类型：
--
作者：
Huang, Xiongyi;Zhuang, Thompson;Groves, John T.
有机异氰酸酯是多功能的中间体，提供了广泛的功能。在这项工作中，我们开发了第一个通过直接C-H活化制备脂肪族异氰酸酯的合成方法。该方法在室温下进行效率高，可用于功能化仲、叔、苯基C-H键，具有良好的产率和官能团相容性。此外，异氰酸酯产物可以很容易地转化为取代脲而无需分离，证明了该方法的合成潜力。为了研究反应机理，我们合成并表征了一种罕见的Mn-IV-NCO中间体，并证明了它能够将异氰酸酯部分转移到烷基自由基上。利用EPR光谱，我们在催化条件下直接观察到了Mn-IV中间体。用手性锰盐催化剂对天牛脂进行异氰化反应，再用苯胺捕获，得到对映体过量51%的尿素产物。这是通过C-H活化不对称合成有机尿素的唯一例子。结合我们的DFT计算，这些结果清楚地表明，C-NCO键是通过Mn-IV-NCO中间体捕获底物自由基形成的。
Organic isocyanates are versatile intermediates that provide access to a wide range of functionalities. In this work, we have developed the first synthetic method for preparing aliphatic isocyanates via direct C-H activation. This method proceeds efficiently at room temperature and can be applied to functionalize secondary, tertiary, and benzylic C-H bonds with good yields and functional group compatibility. Moreover, the isocyanate products can be readily converted to substituted ureas without isolation, demonstrating the synthetic potential of the method. To study the reaction mechanism, we have synthesized and characterized a rare Mn-IV-NCO intermediate and demonstrated its ability to transfer the isocyanate moiety to alkyl radicals. Using EPR spectroscopy, we have directly observed a Mn-IV intermediate under catalytic conditions. Isocyanation of celestolide with a chiral manganese salen catalyst followed by trapping with aniline afforded the urea product in 51% enantiomeric excess. This represents the only example of an asymmetric synthesis of an organic urea via C-H activation. When combined with our DFT calculations, these results clearly demonstrate that the C-NCO bond was formed through capture of a substrate radical by a Mn-IV-NCO intermediate.