One‐Pot Mechanochemical Synthesis of Mono‐ and Bis‐Indolylquinones via Solvent‐Free Multiple Bond‐Forming Processes
Marta Piquero, Cristina Vadillo, Natalia Gullón, Pilar López‐Alvarado, J. Carlos Menéndez
Abstract
Abstract Bis‐indolylquinones are fungal natural products endowed with interesting pharmacological properties. Most of the previously described methodologies in solution for the construction of the bis‐indolylquinone framework show disadvantages associated with long reaction times and difficult, waste‐generating purifications. A one‐pot mechanochemical methodology for the synthesis of indolylquinones was developed, starting from indoles and dihaloquinones in the presence of FeCl 3 or p ‐TsOH as catalysts and Fetizon's reagent as an oxidant. In contrast to solution chemistry, mechanochemical activation allowed the double addition of indole to a quinone substrate in one pot, leading to symmetrical or non‐symmetrical bis‐indolylquinones via a domino processes comprising up to six steps. In terms of sustainability, the method has several advantages over the solution protocol, including much shorter reaction times, no external heating, one‐pot operation, and the absence of chromatography, leading to a drastically better performance in green metrics and demonstrating the application of several principles of green chemistry, in particular principles 2, 3, and 5.