C−H Activation of Unbiased C(sp3)−H Bonds: Gold(I)‐Catalyzed Cycloisomerization of 1‐Bromoalkynes

• Published in: Angewandte Chemie International Edition 2023-06, Vol.62 (26), p.e202305296-n/a
• Main Authors: Miguélez, Rubén, Semleit, Nina, Rodríguez‐Arias, Carlos, Mykhailiuk, Pavel, González, José M., Haberhauer, Gebhard, Barrio, Pablo
• Format: Article
• Language: English
• Subjects: Alkynes; Catalysis; C−H Bond Activation; DFT Calculations; Functional groups; Gold; Gold - chemistry; Gold Catalysis; Isomerization; Molecular Diversity; Vinyl Cation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202305296

Selective functionalization of non‐activated C(sp3)−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(sp3)−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. A gold‐catalyzed intramolecular insertion reaction of strictly unactivated C(sp3)−H bonds is described. The reaction uses readily available starting materials and benefits from extremely simple reaction conditions. A library of structurally diverse scaffolds bearing a C(sp2)−Br bond has been obtained. In addition, an original reaction pathway in gold catalysis involving a concerted insertion on a gold‐stabilized vinylcation has been disclosed.