Entry to 1,2,3,4-Tetrasubstituted Arenes through Addressing the "Meta Constraint" in the Palladium/Norbornene Catalysis.
Entry to 1,2,3,4-Tetrasubstituted Arenes through Addressing the "Meta Constraint" in the Palladium/Norbornene Catalysis.
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DOI：
10.1021/jacs.9b12355
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发表时间：
2020-01
影响因子：
15
通讯作者：
Jianchun Wang;Yun Zhou;Xiaolong Xu;Peng Liu;Guangbin Dong
中科院分区：
文献类型：
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作者：
Jianchun Wang;Yun Zhou;Xiaolong Xu;Peng Liu;Guangbin Dong
具有四个不同邻位取代基的芳烃，即1，2，3，4-四取代芳烃，在生物活性化合物中很常见，但通过传统方法很难获得。通过解决钯/降冰片烯(Pd/NBE)协同催化中的“间位限制”，即难以在芳基卤化物底物中容忍较大的间位取代基，实现了一种模块化和区域选择性的方法来制备1，2，3，4-四取代芳烃。其中一个关键是使用C2-酰胺取代的NBE，实验和计算相结合的研究揭示了它在促进NBE插入和邻位C-H金属化步骤中的作用。范围很广：通过1，4-二取代芳基卤化物，可以将各种亲电剂和亲核剂分别引入邻位和异位，得到各种不对称的四取代四取代芳烃。这种方法的应用已经在几种生物活性化合物的简化合成中得到了证明。
Arenes with four different contiguous substituents, i.e. 1,2,3,4-tetrasubstituted arenes, are commonly found in bioactive compounds, but they are non-trivial to access via conventional methods. Through addressing the "meta constraint" in the palladium/norbornene (Pd/NBE) cooperative catalysis, which is the difficulty of tolerating a sizable meta substituent in aryl halide substrates, here a modular and regioselective approach is realized for preparing 1,2,3,4-tetrasubstituted arenes. One key is the use of a C2-amide-substituted NBE, and a combined experimental and computational study reveals its role in promoting the NBE insertion and the ortho C-H metalation steps. The scope is broad: a variety of electrophiles and nucleophiles could be introduced to the ortho and ipso positions, respectively, with 1,4-disubstituted aryl halides, leading to diverse unsymmetrical contiguous tetrasubstituted arenes. Application of this approach has been demonstrated in streamlined syntheses of several bioactive compounds.