School of Materials Science and Chemical Engineering, Institute of Drug Discovery Technology, Ningbo University, Ningbo 315211, P. R. China.
State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, P. R. China.
Org Biomol Chem. 2022 Sep 28;20(37):7491-7498. doi: 10.1039/d2ob01281b.
A simple and efficient methodology for the first synthesis of tri- and di-fluoromethyl-bis(indolyl)methanols has been demonstrated through a one-pot Friedel-Crafts-type acylation-alkylation of readily available indoles and fluorinated acids. This simple protocol was successfully performed under metal-, additive-, toxic-solvent-, and protective-gas-free conditions, and delivered a wide range of tri- and di-fluoromethyl-bis(indolyl)methanols in moderate to high yields. Notably, this reaction can tolerate diverse vital and reactive functional groups. Furthermore, this one-pot Friedel-Crafts-type acylation-alkylation can be readily expanded to the gram scale with no obvious decrease in the yield, demonstrating its high application potential.
一种简单高效的三氟甲基-和二氟甲基-双（吲哚基）甲醇的合成方法，通过 readily available indoles 和 fluorinated acids 的一锅 Friedel-Crafts 型酰化-烷基化反应得到了展示。该简单的方案在无金属、添加剂、有毒溶剂和保护性气体的条件下成功进行，以中等至高的收率得到了广泛的三氟甲基-和二氟甲基-双（吲哚基）甲醇。值得注意的是，该反应可以容忍多种重要和反应性的官能团。此外，该 Friedel-Crafts 型酰化-烷基化的一锅法可以很容易地扩展到克级规模，产率没有明显下降，显示出其高的应用潜力。
