Fluorinated 1,2,3-Triazoles: Terra Incognita in 1,2,3-Triazoles Chemistry

This review is devoted to the synthesis and application of fluoro-substituted 1,2,3-triazoles. The analysis of the available studies of fluorinated triazoles indicates exceptional value properties especially for biomedical research, despite the significant limitations of synthetic methods of their preparation. In general, it can be noted that today there are only two strategic approaches to obtaining fluorinated triazoles. First, Huisgen 1,3-dipolar cycloaddition, which is significantly limited by stability problems of fluorine-unsaturated dipolarophiles, regioselectivity and low conversion problems. This approach allows preferentially obtaining 4-fluoro-1-substituted triazoles. Second, nucleophilic substitution, which allows obtaining 5-fluoro-1,4-disubstitution, but under rather hard conditions and is also limited by the nature of the substituent. Finally, there are practically no protocols for the preparation difluorotriazoles, and, also, the use of fluoro-substituted 1,2,3-triazoles as regents for further transformations is not enough studied. The analysis of the available studies of fluorinated triazoles indicates exceptional value properties, especially for biomedical research, despite the significant limitations of synthetic preparation methods. In general, it can be noted that today, there are only two strategic approaches to obtaining fluorinated triazoles - Huisgen 1,3-dipolar cycloaddition and nucleophilic substitution.image