A novel atroposelective strategy for the synthesis of quinoline substrates

Among heterocyclic compounds, quinoline scaffold has become an important motif for the development of new pharmacological active compounds. Since the discovery of their antimalarial properties, a large variety of quinolines was found to have interesting physiological activities and displayed attractive applications for pharmaceutical industries. In accordance to the above-mentioned features, a number of methods were developed for their synthesis but enantioselective versions are still lacking in the literature. In the past decades, this question has become even more complex, with the emergence of the less common axial chirality. Within the growing number of articles about atropisomers, the discovery of new synthetic pathways for the synthesis of enantioenriched atropisomers and their use in drug discovery has become a challenging topic in the organic chemistry scenario. In this work, the development of a novel atroposelective strategy for the synthesis of quinoline substrates has been achieved, and in order to obtain high values of enantioselectivity and yields a screening of the reaction conditions has been performed. The design of such strategy has been developed combining an already established methodology for the synthesis of heteroaromatic compounds such as a well-known Friedländer-type quinoline synthesis with chiral Brønsted acid catalysis to obtain the C-C bond formation in an enantioselective fashion.