Direct Catalytic Functionalization of Indazole Derivatives

Abstract

Indazoles are a very important class of N‐containing heterocycles with a wide range of biological and medicinal properties. The presence of different functionalities on indazole moieties enhances its biological activities. Hence, the preparation of indazole compounds bearing functional groups has gained a significant interest to the organic synthetic chemists. A large effort has been made to develop efficient and new methods for the functionalization of indazoles. Direct catalytic functionalization is a very powerful tool for facile synthesis of important indazole derivatives due to its straightforwardness. This review summarizes developments on direct functionalizations of indazoles published in the last two decades.

Visible-light-induced direct 3-ethoxycarbonylmethylation of 2-aryl-2H-indazoles in water

“…7 Consequently, the development of greener and practical methods to construct a variety of 2Hindazole derivatives is highly desirable in medicinal chemistry and organic synthesis. 8 Recently, the direct C3 functionalization of 2H-indazoles using radical reactions has gained great advances. For instance, the radical C3-functionalization of 2-aryl-2H-indazole including the C3-alkylation, 9 C3-benzylation, 10 C3-trifluoromethylation, 11 C3-acylation, 12 C3-arylation, 13 C3-amination, 14 C3-alkoxylation, 15 C3-sulfonylation, 16 C3-thiocyanation, 17 C3cyanoalkylation, 18 C3-phosphonylation, 19 C3-carbamoyla-tion, 20 C3-fluorination, 21 etc., was built up by cross-coupling of the radical sources and heteroaromatic substrates.…”

Recent Developments in the Cyclization of Alkynes and Nitrogen Compounds for the Synthesis of Indole Derivatives

“…[5] Indoles have been studied for over one hundred years and these studies delivered to the scientific community impressive advances in biological properties [6] and synthetic applications of this class of compounds. [7] Although less studied, its derivatives azaindole, [8] carbazole, [9] carboline, [10] indazole, [11] 3H-indole, [12] indoline, [13] indolizine, [14] isoindole, [15] and isoindoline [16] have gained prominence in organic synthesis, medicinal chemistry, materials science, and industry. Because of such an application, the synthesis of indole derivatives has been a subject of several approaches.…”

Oxidative cross-dehydrogenative coupling (CDC) via C(sp2)–H bond functionalization: tert-butyl peroxybenzoate (TBPB)-promoted regioselective direct C-3 acylation/benzoylation of 2H-indazoles with aldehydes/benzyl alcohols/styrenes

“…Indazole functionalization has achieved emerging demand in the fields of organic and medicinal chemistry as the functionalization of indazoles can be rendered into advantageous structural motifs for various medications. 4 Therefore, the development of a new synthetic pathway to introduce various functional groups on 2 H -indazoles leading to an increase in the molecular abundance and the formation of new bioactive molecules, will always be of the utmost importance to medicinal chemistry and drug discovery.…”