Grosso, CarlaBrigas, Amadeude los Santos, Jesus M.Palacios, FranciscoLemos, AmericoPinho e Melo, Teresa M. V. D.2020-07-242020-07-242019-070026-92471434-4475http://hdl.handle.net/10400.1/14304For 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. [GRAPHICS] .engActive pharmaceutical ingredientsCatalytic asymmetric-synthesisCarbonyl-compoundsVibrio-parahaemolyticusIndole alkaloidsIonic liquidsOximesNitrosoalkenesDeoximationMildjournal article10.1007/s00706-019-02421-7