Polyfluoro(aza)aromatic compounds are of interest in various fields of practical applications, such as medicinal and agrochemistry, materials science and advanced technologies. The C–C coupling reactions are known to be a promising synthetic tool to create challenging fluorinated molecules of diverse architectures. In this review, we have summarized the recent advances in the functionalization of polyfluoro(aza)aromatics via both transition metal-catalyzed and metal-free C–C coupling reactions for the period from 2006 to the beginning of 2021. Also, mechanistic features for chemical transformations of fluoroarene scaffolds and new opportunities for practical applications of the designed fluorinated molecules have been highlighted.

The methodology of direct C(sp²)–H functionalization has for the first time been applied as an efficient and advanced approach to carry out C–H/C–H coupling of 2H-imidazole 1-oxides and pyrroles. The atom-economical method used does not require either any auxiliary group in the starting substrates, or catalysis by transition metals. As a result, a number of novel 1H-pyrrol-2-yl-2H-imidazoles, that are particularly of interest in the design of bioactive molecules, have been prepared under mild conditions and in good to excellent yields.

The synthesis of inhibitors for oxidative stress-associated destructive processes based on 2H-imidazole-derived phenolic compounds affording the bifunctional 2H-imidazole-derived phenolic compounds in good-to-excellent yields was reported. In particular, a series of bifunctional organic molecules of the 5-aryl-2H-imidazole family of various architectures bearing both electron-donating and electron-withdrawing substituents in the aryl fragment along with the different arrangements of the hydroxy groups in the polyphenol moiety, namely derivatives of phloroglucinol, pyrogallol, hydroxyquinol, including previously unknown water-soluble molecules, were studied. The structural and antioxidant properties of these bifunctional 5-aryl-2H-imidazoles were comprehensively studied. The redox transformations of the synthesized compounds were carried out. The integrated approach based on single and mixed mechanisms of antioxidant action, namely the AOC, ARC, Folin, and DPPH assays, were applied to estimate antioxidant activities. The relationship “structure-antioxidant properties” was established for each of the antioxidant action mechanisms. The conjugation effect was shown to result in a decrease in the mobility of the hydrogen atom, thus complicating the process of electron transfer in nearly all cases. On the contrary, the conjugation in imidazolyl substituted phloroglucinols was found to enhance their activity through the hydrogen transfer mechanism. Imidazole-derived polyphenolic compounds bearing the most electron-withdrawing functionality, namely the nitro group, were established to possess the higher values for both antioxidant and antiradical capacities. It was demonstrated that in the case of phloroglucinol derivatives, the conjugation effect resulted in a significant increase in the antiradical capacity (ARC) for a whole family of the considered 2H-imidazole-derived phenolic compounds in comparison with the corresponding unsubstituted phenols. Particularly, conjugation of the polyphenolic subunit with 2,2-dimethyl-5-(4-nitrophenyl)-2H-imidazol-4-yl fragment was shown to increase ARC from 2.26 to 5.16 (10⁴ mol-eq/L). This means that the considered family of compounds is capable of exhibiting an antioxidant activity via transferring a hydrogen atom, exceeding the activity of known natural polyphenolic compounds.