School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu, P.R. China.
J Org Chem. 2022 Jan 21;87(2):1086-1097. doi: 10.1021/acs.joc.1c02412. Epub 2022 Jan 11.
The regio- and chemoselective construction of indole bearing an all-carbon center at the C3-position, a versatile bioactive building block, by C(sp)-C(sp) formation with olefins has been achieved through utilization of hexafluoroisopropanol (HFIP) as the protonation reagent and solvent. The catalytic reactions are operationally simple and green compared with previous reports utilizing elaborated olefins and catalysts. This protocol allows for alkylation of a variety of substituted indoles with diverse of styrene type alkenes in excellent yields and with high selectivity. Application of this protocol to the synthesis of drug was pursued and with an improved yield in contrast to previous art. Catalytic kinetics and deuterium-labeling experiments suggest that the rate-determining step involves the protonation of olefin by HFIP to generate carbocation, followed by electrophilic addition to indole derivative.
通过利用六氟异丙醇 (HFIP) 作为质子化试剂和溶剂，实现了在吲哚的 C3-位构建含有全碳中心的区域和化学选择性，这是一种多功能的生物活性构建块。与之前利用精细烯烃和催化剂的报道相比，催化反应操作简单、绿色。该方案允许在各种取代的吲哚与各种取代的苯乙烯型烯烃的烷基化反应中以优异的收率和高选择性进行。该方案已应用于药物的合成，并与之前的文献相比提高了产率。催化动力学和氘标记实验表明，速率决定步骤涉及 HFIP 对烯烃的质子化以生成碳正离子，然后对吲哚衍生物进行亲电加成。
