TfOH-catalyzed regioselective -alkylation of indazoles with diazo compounds

• Published in: Chemical communications (Cambridge, England) Vol. 58; no. 44; pp. 6429 - 6432
• Main Authors: He, Hangli, Yan, Jingyu, Jin, Jingru, Yan, Zhewei, Yan, Qiongjiao, Wang, Wei, Jiang, Haipeng, Wang, Haifeng, Chen, Fener
• Format: Journal Article
• Published: 30.05.2022
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/d2cc01404a

Selective alkylation of indazoles is still a highly challenging topic in chemistry and the synthesis of important molecules. Herein, a novel highly selective N 2 -alkylation of indazoles with diazo compounds is described in the presence of TfOH. Unlike the traditional metal- and base-catalysed version, this protocol highlights the regioselectivity of alkylation of indazoles and a metal-free catalysis system, affording N 2 -alkylated products in good to excellent yields with high regioselectivity ( N 2 / N 1 up to 100/0) and excellent functional group tolerance. Furthermore, a gram scale synthesis was conducted successfully to give rise to the corresponding products. Mechanistic studies through control experiments provide plausible mechanistic proposals. A novel highly selective N 2 -alkylation of indazoles with diazo compounds is described in good to excellent yields with high regioselectivity ( N 2 / N 1 up to 100/0) and excellent functional group tolerance.