Lv Leiyang, Gao Ge, Luo Yani, Mao Kuantao, Li Zhiping
Department of Chemistry, Renmin University of China, Beijing 100872, China.
J Org Chem. 2021 Dec 3;86(23):17197-17212. doi: 10.1021/acs.joc.1c02288. Epub 2021 Nov 1.
The development of methods for the assembly of 1,2,3-triazoles is an important topic due to the broad applications of this motif in various scientific fields. In this work, we demonstrate that the three-component assembly of α-CF carbonyls, NaN, and amines was achieved for the selective construction of a variety of 5-amino -1,2,3-triazoles under transition-metal-free and open-air conditions. The method provides a general and operationally simple route to functionalized biologically important molecules including carbohydrates, nucleosides, and peptides and exhibits broad substrate scopes. We further demonstrate that the -1,2,3-triazoles can be smoothly converted to the regiospecific -2 alkylated 1,2,3-triazole products. Mechanistic studies based on experiments and density functional theory calculations showed that this transformation proceeds via defluorination-initiated programmed substitution/cyclization/H-transfer to give the 4,5-difunctionalized captodative -1,2,3-triazole product.
由于1,2,3-三唑基序在各个科学领域的广泛应用，其合成方法的开发是一个重要的课题。在这项工作中，我们证明了在无过渡金属和露天条件下，通过α-CF羰基、NaN和胺的三组分组装，能够选择性地构建多种5-氨基-1,2,3-三唑。该方法为功能化的具有生物学重要性的分子（包括碳水化合物、核苷和肽）提供了一条通用且操作简单的路线，并且具有广泛的底物范围。我们进一步证明了1,2,3-三唑可以顺利转化为区域特异性的-2烷基化1,2,3-三唑产物。基于实验和密度泛函理论计算的机理研究表明，这种转化是通过脱氟引发的程序取代/环化/H-转移进行的，从而得到4,5-二官能化的两性离子型1,2,3-三唑产物。
