基于8-氨基喹啉导向的钴催化吲哚氘代反应研究

8-Aminoquinoline-guided cobalt-catalyzed deuteration of indole

同位素标记在药物发现过程中发挥着关键作用,它能提高潜在药物分子的性能,应用前景广阔。通过金属催化的C—H活化,H/D交换已被广泛采用为合成同位素标记化合物的关键方法,允许氘的后期掺入,从而避免使用昂贵的标记起始材料。与其他方法相比,过渡金属介导的H/D交换反应相对温和的反应条件和对大量官能团的高耐受性,避免了不常见的副反应。本研究在8-氨基喹啉导向钴催化剂的作用下,氧化银作为催化剂,苯甲醚作为溶剂,氘代乙酸作为氘代试剂在反应温度为100℃时,反应12 h,实现了吲哚酰胺的位置选择性氘代反应,该方法反应条件温和,操作简单,有广泛的底物范围。

Isotope labeling plays a key role in drug discovery,which can improve the performance of potential drug molecules.The application prospect is broad.Through metal-catalyzed C-H activation,H/D exchange has been widely used as a key method to synthesize isotope-labeled compounds,allowing deuterium to be doped in the later stage to avoide expensive labeling starting materials.Compared with other methods,transition metal-mediated H/D exchange reaction has relatively mild reaction conditions and high tolerance to a large number of functional groups,thus avoide frequent and uncommon side reactions.This study achieved a position selective deuteratation reaction of indole amide using silver oxide as catalyst,benzyl ether as solvent,and deuterated acetic acid as deuterated reagent under the guidance of 8-aminoquinoline cobalt catalyst at a reaction temperature of 100℃for 12 hours.The reaction conditions were mild,the operation was simple,and the substrate range was wide.