TEMPO-Mediated Cross-Dehydrogenative Coupling for the Synthesis of Bis(indolyl)methanes

Abstract

A TEMPO-mediated method has been developed for the synthesis of bis(indolyl)-methane derivatives by the cross-dehydrogenative coupling between C(sp³)−H of para-cresol derivatives and C(sp²)−H of indoles in moderate yields under aqueous conditions. This method utilizes toluene derivatives as starting materials, allowing for coupling without the need for further functionalization. The use of environmentally friendly water as a solvent minimizes waste generation. Electron-donating groups such as methyl and methoxy, as well as halogens like fluorine, chlorine, and bromine, exhibit good tolerance in this process. Furthermore, a possible reaction mechanism is proposed to elucidate the formation of BIMs.