General Synthesis of Tri-Carbo-Substituted N2-Aryl-1,2,3-triazoles via Cu-Catalyzed Annulation of Azirines with Aryldiazonium Salts
Fang-Fang Feng, Jun-Kuan Li, Xuan-Yu Liu, Fa-Guang Zhang, Chi Wai Cheung* and Jun-An Ma*
*Department of Chemistry, Tianjin University, Tianjin 300072, P. R. of China, Email:
zhiwei.zhang
tju.edu.cn, majun_an68tju.edu.cn
F.-F. Feng, J.-K. Li, X.-Y. Liu, F.-G. Zhang, C. W. Cheung, J.-A. Ma, J. Org. Chem., 2020, 85, 10872-10883.
DOI: 10.1021/acs.joc.0c01433
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Abstract
A Cu-catalyzed annulation reaction of azirines and aryldiazonium salts provides fully substituted N2-aryl-1,2,3-triazoles. This regiospecific method allows access to a broad spectrum of products substituted with diverse aryl and alkyl moieties.
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proposed mechanism
Details
The article discusses a novel Cu-catalyzed annulation reaction of azirines with aryldiazonium salts to synthesize fully substituted N2-aryl-1,2,3-triazoles. This method addresses the challenge of selectively producing N2-aryl triazoles, which are important in medicinal chemistry, particularly in drug discovery for treating insomnia. Traditional methods often result in unwanted N1-aryl regioisomers. The new approach uses azirines, which are versatile and readily available, to achieve high yields and regiospecificity. The optimized reaction conditions involve using CuBr as the catalyst, DABCO as the base, and acetonitrile as the solvent, achieving up to 93% yield. The protocol is compatible with various functional groups and allows for large-scale synthesis. Additionally, the triazole products can be further derivatized, expanding their utility in creating drug-like molecules and novel chiral ligands. Preliminary mechanistic studies suggest a radical pathway. This method offers a streamlined and efficient route to synthesize diverse N2-aryl-1,2,3-triazoles, enhancing their potential applications in pharmaceuticals and materials science.
Key Words
ID: J42-Y2020
