Zhang Siqi, Zhao Liang
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China.
Nat Commun. 2023 Oct 24;14(1):6741. doi: 10.1038/s41467-023-42602-x.
The reaction mechanism of the historic copper-catalyzed Glaser coupling has been debated to be based on redox cycles of Cu ions in specific oxidation states or on a radical mechanism based on Cu(0)/Cu(I). Here, the authors demonstrate two coexisting Glaser coupling pathways which can be differentiated by anaerobic/irradiation or aerobic reaction conditions. Without O, copper(I) acetylides undergo a photo-excited pathway to generate highly reactive alkynyl radicals, which combine together to form a homo-coupling product or individually react with diverse X-H (X = C, N, O, S and P) substrates via hydrogen atom transfer. With O, copper(I) acetylides are oxidized to become a Cu-acetylide/Cu-O merged Cu(I/II) intermediate for further oxidative coupling. This work not only complements the radical mechanism for Glaser coupling, but also provides a mild way to access highly energetic alkynyl radicals for efficient organic transformations.
具有历史意义的铜催化格拉泽偶联反应的机理一直存在争议，有人认为其基于特定氧化态的铜离子的氧化还原循环，也有人认为是基于Cu(0)/Cu(I)的自由基机理。在此，作者证明了两种共存的格拉泽偶联途径，这两种途径可通过厌氧/辐照或有氧反应条件来区分。在没有氧气的情况下，炔铜经历光激发途径生成高活性炔基自由基，这些自由基相互结合形成均偶联产物，或通过氢原子转移分别与各种X-H（X = C、N、O、S和P）底物反应。在有氧气的情况下，炔铜被氧化成为炔铜/铜-氧合并的Cu(I/II)中间体，用于进一步的氧化偶联。这项工作不仅补充了格拉泽偶联的自由基机理，还提供了一种温和的方法来获得高活性炔基自由基，以实现高效的有机转化。
