Wang Hao, Fu Lei, Zhou Chunlin, Li Gang
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences (CAS) 155 West Yang-Qiao Road Fuzhou Fujian 350002 China
Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University Shanghai 200240 China.
Chem Sci. 2022 Jul 5;13(29):8686-8692. doi: 10.1039/d2sc01834a. eCollection 2022 Jul 29.
The classic electrophilic bromination leads to - and -bromination of anilines due to their electron-rich properties. Herein we report the development of an unprecedented Pd-catalyzed -C-H bromination of aniline derivatives using commercially available -bromophthalimide (NBP), which overcomes the competing /-selectivity of electrophilic bromination of anilines. The addition of acid additives is crucial for the success of this reaction. A broad range of substrates with various substitution patterns can be tolerated in this reaction. Moreover, benzoic acid derivatives bearing complex substitution patterns are also viable with this mild bromination reaction, and -C-H chlorination is also feasible under similar reaction conditions. The ease of the directing group removal and subsequent diverse transformations of the brominated products demonstrate the application potential of this method and promise new opportunities for drug discovery.
经典的亲电溴化反应由于苯胺具有富电子性质，会导致苯胺发生邻位和对位溴化。在此，我们报道了一种前所未有的钯催化苯胺衍生物的间位C-H溴化反应，该反应使用市售的N-溴代邻苯二甲酰亚胺（NBP），克服了苯胺亲电溴化反应中竞争的邻/对选择性。添加酸性添加剂对该反应的成功至关重要。该反应可以耐受具有各种取代模式的广泛底物。此外，具有复杂取代模式的苯甲酸衍生物也适用于这种温和的溴化反应，并且在类似的反应条件下间位C-H氯化反应也是可行的。导向基团易于去除以及溴化产物随后的多样转化证明了该方法的应用潜力，并为药物发现带来了新机遇。
