Access to 2-substituted-2H-indazoles via a copper-catalyzed regioselective cross-coupling reaction

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.