Access to 2-substituted-2H-indazolesviaa copper-catalyzed regioselective cross-coupling reaction

Abstract

A CuCl catalyzed C-N cross-coupling reaction using commercially available 1H-indazoles with diaryliodonium salts is described. The methodology features ample structural versatility, affording 2-substituted-2H-indazole in good yields and complete N(2)-regiocontrol. Furthermore, the utility of the reaction was demonstrated in the synthesis of a known estrogen receptor β agonist. Mechanistic studies using density functional theory calculations suggested that the complete regioselectivity can be attributed to the only weak base TfO in our system which could not deprotonate indazoles, and the catalyst oxidation process would be the rate-determining step.

Diaryliodoniums Salts as Coupling Partners for Transition-Metal Catalyzed C- and N-Arylation of Heteroarenes

“…2-substituted-2H-indazoles have been recognized as biologically privileged structures, exhibiting a wide range of biological properties such as anticancer activities. Reflecting this, their challenging synthesis under mild conditions was reported by Pan in 2018 [120]. Compared to the previously described C-N cross-coupling reaction starting from 1H indazoles, the use of hypervalent iodine reagent under the catalysis of copper led to N2 arylation in high selectivity.…”

Direct Catalytic Functionalization of Indazole Derivatives

“…In this method, 1H-indazoles (30 a) reacted with hypervalent iodine reagents such as p-tolyl (mesityl)iodonium triflate in presence of CuCl catalyst in dichloromethane solvent at 120°C for 12 h to afford 2-aryl-2H-indazoles (30 b) with moderate to very high yields (Scheme 30). [90] Electron-withdrawing as well as electron-donating substituents at C-4 to C-6 positions of 1H-indazoles were showing compatibility with this reaction and produced good to excellent yields. The group also demonstrated that both electron-withdrawing and electron-donating substituents at meta-and para-positions of the phenyl ring of diaryliodonium salt smoothly produced 2-arylated-2H-indazoles.…”

Synthesis and Photoluminescent Properties of 2-(3-Carboxymethylindazol-1-yl)anilines

“…Due to great practical importance of N-arylated indazoles, over the past two decades methods for their design have been studied in detail and developed using both base and transition metal catalysis [14][15][16][17][18][19]. N-Arylation reactions of 1H-indazoles can proceed at both nitrogen atoms [14][15][16]. However, as a rule, the reaction proceeds regioselectively at the N 1 atom of the indazole ring [17][18][19].…”