Concise Report

Trifluoromethylselenylative Difunctionalization of Arynes with [Me4N][SeCF3]

Hao-Nan Wang, Fu-Yan Xiao, Yu-Wei Rao, and Cheng-Pan Zhang*

A general protocol for the trifluoromethylselenylative difunctionalization of aryne with the nucleophilic [Me4N][SeCF3] reagent is described. The NiCp2-catalyzed cross-couplings of o-silylaryl triflates, [Me4N][SeCF3], and CsF with H2O/CH3CN, D2O/CD3CN, and n-C4F9I or C6F13Br or CCl4 afforded the hydrotrifluoromethylselenylated products, deuterotrifluoromethylselenylated products, and halotrifluoromethylselenylated products, respectively, while the metal-free reaction of o-silylaryl triflates and [Me4N][SeCF3] with NFSI provided the bis(trifluoromethylselenylated) products. These reactions allowed for the facile synthesis of diverse difunctionalized SeCF3 products in good yields, which are unprecedented and difficult to synthesize by other methods. In the Ni-catalyzed reactions, the key aryne intermediate is generated from o-silylaryl triflate in the presence of fluoride ion, coordinates with the nickel catalyst, undergoes ligand exchange with the ?SeCF3 anion, and is inserted into the carbon-carbon triple bond to form an o-trifluoromethylselenylaryl-nickel complex, which is then protonated with H2O/CH3CN to yield the hydrotrifluoromethylselenylated product, deuterated with D2O/CD3CN to produce the deuterotrifluoromethylselenylated product, or halogenated with n-C4F9I, C6F13Br or CCl4 to afford the halotrifluoromethylselenylated product. In the metal-free reaction, the ?SeCF3 anion is first oxidized with NFSI to yield ?SeCF3 radical and fluoride ion, which activates o-silylaryl triflate in situ to form the aryne species, followed by radical addition with ?SeCF3 and subsequent trapping by another ?SeCF3 radical to produce the bis(trifluoromethylselenylated) product. The moisture-sensitive [Me4N][SeCF3] salt was successfully tolerated in the reactions with H2O or D2O. This work further demonstrated the rich chemistry of [Me4N][SeCF3] and the power of aryne-based functionalization as a linchpin step in the production of multi-substituted SeCF3-arenes.

Arynes | Deuterium | Halogen | Trifluoromethylselenylation | Difunctionalization | Nickel | Radical | Cross-Coupling

[Me4N][SeCF3]對芳炔的三氟甲硒基(雙)官能團化反應研究

含氟有機化合物在藥物化學中具有重要地位，三氟甲硒基（SeCF3）作為兼具氟和硒特性的官能團，因其獨特的理化性質和生物活性，成為近年來研究的熱點。然而，由于SeCF3小分子的合成方法學尚不成熟，限制了其在藥物化學中的深層次應用，導致目前尚無含該基團的藥物問世。面對這一挑戰，武漢理工大學張成潘團隊致力于開發溫和、高效的含SeCF3化合物的合成方法，并在該領域做出了系統性貢獻（Org. Lett. 2017, 19, 3919-3922; ACS Sustainable Chem. Eng. 2018, 6, 1327-1335; Org. Chem. Front. 2019, 6, 2732-2737; Org. Lett. 2019, 21, 10013-10017; Org. Lett. 2020, 22, 6016-6020; ChemMedChem 2021, 16, 3177-3180; Org. Chem. Front. 2022, 9, 2220-2227; Chem. Commun. 2022, 58, 9238-9241; J. Org. Chem. 2023, 88, 9372-9380; Org. Lett. 2023, 25, 7884-7889; Chem. Commun. 2025, 61, 15606-15609）。

最近，張成潘、王浩男及肖福艷等報道了一種由NiCp2催化的芳炔三氟甲硒基(雙)官能團化反應。該研究以鄰三甲基硅芳基三氟甲磺酸酯為芳炔前體，以[Me4N][SeCF3]和CsF為反應試劑。通過對反應條件的精準調控（如使用H2O/CH3CN、D2O/CD3CN以及含有全氟碘丁烷、全氟溴己烷或四氯化碳的混合溶劑體系），分別高效地實現了芳炔的氫化、氘代及鹵代三氟甲硒基化。此外，該團隊以N-氟代雙苯磺酰亞胺（NFSI）為氧化劑，實現了[Me4N][SeCF3]對芳炔的雙三氟甲硒基官能團化反應（圖1）。機理研究表明，這些反應可能涵蓋了兩種路徑：在鎳催化體系中，反應經由配合物7遷移插入過程生成關鍵的三氟甲硒基芳基鎳中間體8，隨后中間體8與不同親電試劑反應，實現產物的多樣化構建；另一方面，無金屬介導的雙三氟甲硒基化反應則遵循自由基機理（圖2）。這一合成策略不僅實現了一系列SeCF3雙官能團化產物的簡便合成與高價值轉化，更深層次地揭示了[Me4N][SeCF3]試劑在復雜分子構筑中的反應潛力。該研究進一步拓展了芳炔雙官能團化的應用范疇，為多取代芳烴的結構多樣性合成提供了新思路。

圖 1 綜合摘要圖

圖 2 反應機理圖

上述研究結果作為Report發表于Chin. J. Chem. (2026, 44, 979-986, DOI: 10.1002/cjoc.70432)。該項工作得到了武漢理工大學、湖北省自然科學基金的資助。

認識本文的作者們

Left to Right: Hao-Nan Wang, Fu-Yan Xiao, Yu-Wei Rao, Cheng-Pan Zhang

張成潘教授簡介

武漢理工大學 化學化工與生命科學學院

張成潘，武漢理工大學教授、博士生導師。2011年于中科院上海有機所獲得博士學位，隨后在美國夏威夷大學和德州農工大學從事博士后研究；2014年入職武漢理工大學。主要從事有機氟化學、锍鹽化學和藥物化學方面的研究。已發表SCI論文100余篇，被引用4600多次。先后主持國家自然科學基金、湖北省自然科學基金和企業橫向課題等30余項。先后入選湖北省各類省級人才計劃，武漢市青年科技晨光計劃，武漢理工大學“15551人才工程”青年拔尖人才，湖北省科技副總、濟南市科技副總等。2019年國際化學元素周期表年（IYPT 2019）為锿元素代言（http://www.chemsoc.org.cn/IYPT2019/a3122.html）。