School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
Nat Commun. 2017 Mar 20;8:14801. doi: 10.1038/ncomms14801.
Benzothiophenes are heterocyclic constituents of important molecules relevant to society, including those with the potential to meet modern medical challenges. The construction of molecules would be vastly more efficient if carbon-hydrogen bonds, found in all organic molecules, can be directly converted into carbon-carbon bonds. In the case of elaborating benzothiophenes, functionalization of carbon-hydrogen bonds at carbon-number 3 (C3) is markedly more demanding than at C2 due to issues of regioselectivity (C3 versus C2), and the requirement of high temperatures, precious metals and the installation of superfluous directing groups. Herein, we demonstrate that synthetically unexplored but readily accessible benzothiophene S-oxides serve as novel precursors for C3-functionalized benzothiophenes. Employing an interrupted Pummerer reaction to capture and then deliver phenol and silane coupling partners, we have discovered a directing group-free method that delivers C3-arylated and -alkylated benzothiophenes with complete regioselectivity, under metal-free and mild conditions.
苯并噻吩是对社会具有重要意义的分子的杂环成分，其中包括有可能应对现代医学挑战的分子。如果能够直接将所有有机分子中都存在的碳氢键转化为碳碳键，那么分子的构建效率将大大提高。在苯并噻吩的构建中，由于区域选择性（C3 与 C2）和高温、贵金属以及过多导向基团安装的要求，碳氢 3 位（C3）的碳氢键官能化比 C2 位要求更高。在此，我们证明了以前在合成上尚未开发但易于获得的苯并噻吩 S-氧化物可用作 C3 功能化苯并噻吩的新型前体。我们采用中断的 Pummerer 反应捕获并随后提供酚和硅烷偶联试剂，发现了一种无需导向基团的方法，该方法在无金属和温和条件下，以完全的区域选择性得到 C3-芳基化和 C3-烷基化的苯并噻吩。
