Electrochemically Promoted Regioselective C3─H Trifluoro/Difluoro-methylation of 2H-Indazoles at Room Temperature

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