Natural deep eutectic solvents in the hetero-Diels–Alder approach to bis(indolyl)methanes.

For the first time, the use of natural deep eutectic solvents (NADES) as reaction media to carry out hetero-Diels–Alder reactions is disclosed. This allowed to improve the efficiency and sustainability of the synthetic approach to bis(indolyl)methanes (BIMs) based on bis-hetero-Diels–Alder/conjugate addition reactions of nitroso- and azoalkenes with indoles. The ternary mixture of H₂O with choline chloride/glycerol allowed the tuning of the physical properties of this NADES leading to a better solvent system, affording the target hydroxyiminomethyl- and hydrazonomethyl-BIMs, in much shorter reaction times, higher efficiency and easier isolation procedures. Furthermore, the direct access to carbonyl-BIMs was possible when 3-methyl-1-tert-butoxycarbonyl azoalkenes were used. [ABSTRACT FROM AUTHOR]