García Abellán, Susana De Vos, Dirk Beckers, Igor 2019 2019 This work focuses on the coupling of indoles via C–H activation, due to their importance in bioactive molecules such as pharmaceuticals, for avoiding long synthetic pathways with multiple wasteful reaction septs. This research focuses on the use of oxygen as a green alternative for the oxidation of the Pd-catalyst, which generates H2O as an environmentally harmless side-product. In this work, the Pd-catalyzed C–H/C–H coupling of indoles was demonstrated with oxygen as the oxidant, resulting in a sustainable reaction with H2O as the only stoichiometric by-product. The asymmetric 1,1'-methyl-2,3'-bisindole coupling product was obtained in 88% yield at a low temperature of 40°C. The catalytic activity was increased, allowing a decrease in Pd-loading from 5 to 1 mol% compared to the state-of-the-art. Furthermore, it was shown that the regioselectivity of the reaction can be influenced by changing the electronic properties of the carboxylate ligand. A decrease in reactivity was observed for indole substrates with lower electron density (indole and 1-acetylindole), which indicates that the reaction occurs via an electrophilic attack of the Pd-catalyst.<br /><br />