One-pot Three-component Reaction For Highly Selective Synthesis Of 1-polyfluoroaryl-1,2,3-triazole Compounds

Fluorine is the most electronegative element. The introduction of a fluorine atom or a fluorine-containing group into organic molecules can effectively modify the acidity, polarity, dipole moment, lipophilicity and metabolic stability of these substances. Therefore, the synthesis of organic fluorine compounds has attracted considerable intensive attention and has gradually become one of the hot fields in the synthetic organic chemistry.1,2,3-triazoles scaffolds are ubiquitous structural moieties in the synthetic chemistry, which find widespread applications in medicinal chemistry and materials science. Therefore, researchers make great effort to the synthesis of organofluroine compounds. At present, there are a lot of methods for the synthesis of 1,2,3-triazoles, however, there are few examples for introducing polyfluoroaryl groups to 1,2,3-triazoles. So, the exploration of the facile method for efficient construction of such compounds has become an important topic in the field of organic chemical synthesis.In this dissertation, we have successfully developed a simple and efficient approach for the synthesis of 1-polyfluoroaryl-1,2,3-triazoles via a one-pot three-component tandem reaction. The reaction shows high generality and functional group tolerance, and gives 21 examples up to 92% yield. In the mechanism study, the intermediate polyfluoroarylated azide compound was confirmed by the NMR technology, which produced in situ by the selective C-F bond cleavage of polyfluoroarene with sodium azide, not only avoiding isolation and handling of potentially unstable and dangerous organic azides, but also reducing the complexity and improving the efficiency of the reaction. Such one-pot three-component cascade reaction may be considered to be an efficient strategy in the organic chemistry, which is promising for efficient construction of other drug modules.