Although highly reactive (1H-indol-3-yl)methyl electrophiles such as (1H-indol-3-yl)methyl halides are potential precursors for the synthesis of various indole derivatives, some researchers have reported difficulties in their preparation due to concomitant undesired dimerization/oligomerization. Nevertheless, there have been some reports on the preparation of (1H-indol-3-yl)methyl halides. To resolve this contradiction, all the previously reported preparations of (1H-indol-3-yl)methyl halides were examined. However, we could not reproduce any of these preparations, and we revised several structures of indole derivatives. Here we show the rapid (0.02 s) and mild (25 °C) generation of an (1H-indol-3-yl)methyl electrophile that enables the rapid (0.1 s) and mild (25 °C) nucleophilic substitution in a microflow reactor. Eighteen unprotected indole analogues can be successfully synthesized using the developed microflow nucleophilic substitution with various nucleophiles.

尽管高反应性 (1 H -indol-3-yl) 甲基亲电子试剂如 (1 H -indol-3-yl) 甲基卤化物是合成各种吲哚衍生物的潜在前体，但一些研究人员报告说，由于以下原因，它们的制备存在困难伴随不希望的二聚化/寡聚化。尽管如此，已有一些关于(1 H -indol-3-yl)甲基卤化物制备的报道。为了解决这一矛盾，对所有先前报道的 (1 H -indol-3-yl)methyl halides的制备进行了检查。然而，我们无法重现这些制剂中的任何一种，我们修改了几种吲哚衍生物的结构。在这里，我们展示了快速 (0.02 s) 和温和 (25 °C) 的 (1 H-indol-3-yl)methyl 亲电子试剂，可在微流反应器中实现快速 (0.1 s) 和温和 (25 °C) 的亲核取代。使用开发的微流亲核取代与各种亲核试剂，可以成功合成十八种未保护的吲哚类似物。