Transition-metal-catalyzed direct site-selective functionalization of arene C-H bonds has emerged as an innovative approach for building the core structure of pharmaceutical agents and other versatile complex compounds. However, para-selective C-H functionalization has seldom been explored, only a few examples, such as steric-hindered arenes, electron-rich arenes, and substrates with a directing group, have been reported to date. Here we describe the development of a ruthenium-enabled para-selective C-H difluoromethylation of anilides, indolines, and tetrahydroquinolines. This reaction tolerates various substituted arenes, affording para-difluoromethylation products in moderate to good yields. Results of a preliminary study of the mechanism indicate that chelation-assisted cycloruthenation might play a role in the selective activation of para-C_Ar-H bonds. Furthermore, this method provides a direct approach for the synthesis of fluorinated drug derivatives, which has important application for drug discovery and development.

中文翻译：

---

钌（II）能够实现苯甲酸酯及其衍生物的对位选择性CH二氟甲基化。

芳烃CH键的过渡金属催化直接位点选择性官能化已成为一种创新方法，可用于构建药剂和其他通用复杂化合物的核心结构。但是，很少研究对位选择性CH的官能化，迄今仅报道了少数几个例子，例如空间受阻的芳烃，富电子的芳烃和带有导向基团的底物。在这里，我们描述了钌，吲哚啉和四氢喹啉的钌使能的对位选择性CH二氟甲基化的发展。该反应耐受各种取代的芳烃，以中等至良好的产率提供对二氟甲基化产物。对该机制的初步研究结果表明，螯合辅助的环化钌可能在对C的选择性激活中起作用_Ar -H键。此外，该方法提供了合成氟化药物衍生物的直接方法，其对于药物发现和开发具有重要的应用。