Debrauwer Vincent, Leito Ivo, Lõkov Märt, Tshepelevitsh Sofja, Parmentier Michael, Blanchard Nicolas, Bizet Vincent
Université de Haute-Alsace, Université de Strasbourg, CNRS, LIMA, UMR 7042, 68000 Mulhouse, France.
Institute of Chemistry, University of Tartu, Tartu 50411, Estonia.
ACS Org Inorg Au. 2021 Jul 6;1(2):43-50. doi: 10.1021/acsorginorgau.1c00010. eCollection 2021 Dec 1.
Structural diversity in heterocyclic chemistry is key to unlocking new properties and modes of action. In this regard, heterocycles embedding emerging fluorinated substituents hold great promise. Herein is described a strategy to access 2-SF-(aza)indoles for the first time. The sequence relies on the radical addition of SFCl to the alkynyl π-system of 2-ethynyl anilines followed by a cyclization reaction. A telescoped sequence is proposed, making this strategy very appealing and reproducible on a gram scale. Downstream functionalizations are also demonstrated, allowing an easy diversification of N- and C3-positions. Ames test, p , log , and differential scanning calorimetry measurements of several fluorinated 2-Rf-indoles are also disclosed. These studies highlight the strategic advantages that a C2-pentafluorosulfanylated motif impart to a privileged scaffold such as an indole.
杂环化学中的结构多样性是解锁新性质和作用模式的关键。在这方面，嵌入新兴含氟取代基的杂环具有巨大潜力。本文首次描述了一种合成2-五氟硫烷基（氮杂）吲哚的策略。该反应序列基于SFCl对2-乙炔基苯胺的炔基π-体系进行自由基加成，随后进行环化反应。本文提出了一种串联反应序列，使该策略极具吸引力且可在克级规模上重现。还展示了下游官能团化反应，可轻松实现N位和C3位的多样化。还公开了几种氟化2-Rf-吲哚的艾姆斯试验、p、log以及差示扫描量热法测量结果。这些研究突出了C2-五氟硫烷基 motif赋予诸如吲哚这类优势骨架的战略优势。
