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

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.