Diastereoselective multicomponent synthesis of dihydroisoindolo[2,1-a]quinolin-11-ones mediated by eutectic solvents.

Abstract

In this contribution, a series of dihydroisoindolo[2,1-a]quinolin-11-ones was synthesized by a one-pot multicomponent Povarov reaction starting from anilines, alkenes (trans-anethole, methyl eugenol and indene) and 2-formylbenzoic acid. Different eutectic solvents bearing Lewis or Brønsted acids were evaluated as reaction media and catalysts for the model reaction employing p-toluidine and trans-anethole finding that the eutectic mixture ChCl/ZnCl2 (1/2) allowed the obtention of the target compound in 77% isolated yield. Under the optimized reaction conditions, 20 derivatives were obtained in good to moderated yields using meta- and para-susbstituted anilines, while the corresponding ortho-analogs followed a different pathway affording isoindolinones. In addition, the eutectic mixture was reused in six cycles without observing a detrimental catalytic activity. This methodology features mild reaction conditions, short reaction time, simple work-up, and utilization of a reusable solvent; and provides straightforward and diastereoselective access to these alkaloid-like heterocyclic molecules.