Oxidant-Switched Palladium-Catalyzed Regioselective Mono- versus Bis- ortho -Aroylation of 1-Aryl-1 H -indazoles with Aldehydes via C-H Bond Activation.

A highly efficient oxidant-switched palladium-catalyzed regioselective C (sp 2 ) -H/C (sp 2 ) -H cross-dehydrogenative coupling (CDC) for direct mono/bis - ortho -aroylation of substituted 1-phenyl-1 H -indazoles 1a-j with various substituted aldehydes 3a-t via C (sp 2 ) -H bond activation has been developed. In this study, Pd-catalyzed chelation-assisted mono- or bis-aroylation of substituted 1-phenyl - 1 H -indazoles depends on the type of oxidant being used for the CDC reaction. While mono- ortho -aroylation of substituted 1-phenyl-1 H -indazole was obtained using dicumylperoxide (DCP) as the oxidant, the bis- ortho -aroylation product has been afforded by the use of tert -butyl hydroperoxide (TBHP). Regardless of the greater activity at the C-3 position of 1 H -indazoles, the greater coordinating capacity of the N atom directed the aroylating group to the ortho position, leaving behind the nondirected metalation pathway. The Pd-catalyzed operationally simplified methodology proceeded in the presence of oxidants with either DCP or TBHP in dichloroethane as the solvent at 110 °C for 16 h, which generated a miscellaneous variety of monosubstituted o -benzoyl/acyl-1-aryl-1 H -indazoles 4a-t / 5a-i and bis-substituted o -benzoyl-1-aryl-1 H -indazoles 6a-j in ≤88% yields. The probable mechanistic pathway involves a free radical chelation-assisted approach that could be accomplished by the addition of an in situ -generated oxidant-promoted benzoyl/acyl radical to the ortho position of 1-phenyl-1 H -indazoles. A wide range of substrates, a high functional group tolerance, gram-scale synthesis, control/competitive experiments, and a variety of synthetic applications further exemplify the versatility of the developed methodology.