Zhou Changsheng, Huang Ming, Yao Yufeng, Chen Chunyu, Yi Xin, Yang Ke-Fang, Lai Guo-Qiao, Xuan Wenjing, Zhang Pinglu
Hangzhou Normal University, College of Material Chemistry and Chemical Engineering, Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, Key Laboratory of Organosilicon Material Technology of Zhejiang Province, Hangzhou 311121, China.
Westlake University, School of Engineering, Hangzhou 310030, China.
Org Biomol Chem. 2023 Dec 13;21(48):9534-9541. doi: 10.1039/d3ob01570j.
Hydroarylation of alkenes is one of the most straightforward and atom-economical strategy for the construction of multi-aryl-substituted alkanes, but systematic studies have been limited to transition metal catalysis. Here we report a hexafluoroisopropanol (HFIP)-promoted hydroarylation of alkenes with indoles without the presence of transition metal catalysts or any additive. HFIP was the only reagent used in this work, and could be easily removed evaporation, and recovered distillation in industry settings. This reaction was shown to provide an efficient, clean and operationally simple procedure with a remarkable substrate scope and versatile transformations, delivering a variety of multi-aryl alkanes incorporating the indole motif. In preliminary studies, several of these products showed biologically activity against cells from an array of human cancer cell lines. A mechanistic study was also carried out and suggested that the quinone methide might be the key intermediate. And in contrast to the conclusions of a previous report, the current work suggested that protonation by HFIP might not be the rate-determining step.
烯烃的氢芳基化反应是构建多芳基取代烷烃最直接且原子经济性最高的策略之一，但系统研究一直局限于过渡金属催化。在此，我们报道了一种在无过渡金属催化剂或任何添加剂存在的情况下，由六氟异丙醇（HFIP）促进的烯烃与吲哚的氢芳基化反应。HFIP是本工作中唯一使用的试剂，在工业环境中可通过蒸发轻松除去，并通过蒸馏回收。该反应被证明提供了一种高效、清洁且操作简单的方法，具有显著的底物范围和多样的转化，可生成多种包含吲哚基序的多芳基烷烃。在初步研究中，其中几种产物对一系列人类癌细胞系的细胞显示出生物活性。还进行了机理研究，表明醌甲基化物可能是关键中间体。与之前一份报告的结论相反，当前工作表明HFIP的质子化可能不是速率决定步骤。
