Departamento de química Orgánica e Inorgánica, Universidad de Oviedo, Julian Clavería 8, 33006, Oviedo, Spain.
Institut für Organische Chemie, Universität Duisburg-Essen, Universitätsstraße 7, 45117, Essen, Germany.
Angew Chem Int Ed Engl. 2023 Jun 26;62(26):e202305296. doi: 10.1002/anie.202305296. Epub 2023 May 12.
Selective functionalization of non-activated C(sp )-H bonds is a major challenge in chemistry, so functional groups are often used to enhance reactivity. Here, we present a gold(I)-catalyzed C(sp )-H activation of 1-bromoalkynes without any sort of electronic, or conformational bias. The reaction proceeds regiospecifically and stereospecifically to the corresponding bromocyclopentene derivatives. The latter can be readily modified, comprising an excellent library of diverse 3D scaffolds for medicinal chemistry. In addition, a mechanistic study has shown that the reaction proceeds via a so far unknown mechanism: a concerted [1,5]-H shift / C-C bond formation involving a gold-stabilized vinylcation-like transition state.
非活性 C(sp 3 )-H 键的选择性功能化是化学领域的一个主要挑战，因此通常使用官能团来增强反应性。在这里，我们提出了一种无任何电子或构象偏向的金（I）催化 1-溴炔烃的 C(sp 3 )-H 活化。该反应具有区域和立体选择性，得到相应的溴环戊烯衍生物。后者可以很容易地进行修饰，构成了一个用于药物化学的多样化 3D 支架的优秀库。此外，一项机理研究表明，该反应通过一种迄今为止未知的机制进行：涉及金稳定的乙烯基阳离子样过渡态的协同 [1,5]-H 迁移/C-C 键形成。
