Electrochemically Promoted Regioselective C3–H Trifluoro/Difluoromethylation of 2H-Indazoles at Room Temperature

Dedicated to Prof. B. C. Ranu on the occasion of his 75th Birthday

Abstract

A green and sustainable electrochemical approach is developed for the regioselective C3–H trifluoro/difluoromethylation of 2H-indazoles at room temperature. Relatively less expensive C-soft (+)/Ni-foam (–) electrodes are utilized to selectively functionalize the 2H-indazoles effectively by avoiding the use of any external oxidant and transition-metal salt. Moreover, along with the C3–H trifluoromethylation, for the very first time, direct C3–H difluoromethylation of 2-phenyl-2H-indazoles is accomplished. Diverse C3–H trifluoro/difluoromethylated 2H-indazoles having an array of functionalities are successfully synthesized in moderate to very good yields. As an application, a precursor of both an estrogen receptor ligand and an acetyl Co-A carboxylase inhibitor is synthesized. A plausible reaction mechanism is proposed based on control experiments and cyclic voltammetry studies.

Key words

trifluoromethylation - difluoromethylation - regioselective - 2H-indazole - transition-metal-free - external-oxidant-free

Publication History

Received: 12 August 2024

Accepted after revision: 25 September 2024

Accepted Manuscript online:
25 September 2024

Article published online:
31 October 2024

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These methods required prefunctionalization of the starting material and multistep reactions to afford difluoromethylated 2H-indazoles, see
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