Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin 130022 (China); The University of Chinese Academy of Sciences, Beijing 100864 (China).
Chemistry. 2014 Feb 17;20(8):2373-81. doi: 10.1002/chem.201302857. Epub 2014 Jan 21.
The development of a highly efficient and practical protocol for the direct C-N coupling of H-tetrazole and boronic acid was presented. A careful and patient optimization of a variety of reaction parameters revealed that this conventionally challenge reaction could indeed proceed efficiently in a very simple system, that is, just by stirring the tetrazoles and boronic acids under oxygen in the presence of different Cu(I) or Cu(II) salts with only 5 mol % loading in DMSO at 100 °C. Most significantly, the reaction could proceed very smoothly in a regiospecific manner to afford the 2,5-disubstituted tetrazoles in high to excellent yields. A mechanistic study revealed that both tetrazole and DMSO are crucial for the generation of catalytically active copper species in the reaction process in addition to their role as reactant and solvent, respectively. It is demonstrated that in the reaction cycle, the Cu(I) catalyst could be oxidized to Cu(II) by oxygen to form a [CuT2D] complex (T = tetrazole anion; D = DMSO) through an oxidative copper amination reaction. The Cu(II) complex thus formed was confirmed to be the real catalytically active copper species. Namely, the Cu(II) complex disproportionates to aryl Cu(III) and Cu(I) in the presence of boronic acid. Facile elimination of the Cu(III) species delivers the C-N-coupled product. The results presented herein not only provide a reliable and efficient protocol for the synthesis of 2,5-disubstituted tetrazoles, but most importantly, the mechanistic results would have broad implications for the de novo design and development of new methods for Cu-catalyzed coupling reactions.
本文提出了一种高效实用的直接 C-N 偶联 H-四唑和硼酸的方法。通过仔细和耐心地优化各种反应参数，发现该常规挑战性反应确实可以在非常简单的体系中高效进行，即在氧气存在下，只需在 100°C 下用不同的 Cu(I)或 Cu(II)盐在 DMSO 中以 5 mol%的负载量搅拌四唑和硼酸。最重要的是，该反应可以以高区域选择性的方式进行，以高至优异的收率得到 2,5-取代的四唑。机理研究表明，除了分别作为反应物和溶剂之外，四唑和 DMSO 对于在反应过程中生成催化活性铜物种都是至关重要的。实验证明，在反应循环中，Cu(I)催化剂可以被氧气氧化为 Cu(II)，通过氧化铜氨化反应形成[CuT2D]配合物（T = 四唑阴离子；D = DMSO）。形成的 Cu(II)配合物被确认为真正的催化活性铜物种。也就是说，在硼酸存在下，Cu(II)配合物歧化生成芳基 Cu(III)和 Cu(I)。Cu(III)物种的易消除提供了 C-N 偶联产物。本文的结果不仅为 2,5-取代四唑的合成提供了可靠高效的方法，而且最重要的是，机理结果将对新型铜催化偶联反应的从头设计和开发具有广泛的意义。
