One-pot access to quinoline–chalcone hybrids via the iron-catalyzed aerobic oxidative sp3 C-H activation of unactivated alkylquinolines

Abstract

Quinoline-chalcone hybridization is a versatile strategy in anticancer drug discovery by integrating the complementary biological and physicochemical features of quinoline and chalcone scaffolds, enabling enhanced activity and broad structural diversification. Here, we report an iron-catalyzed one-pot approach for the direct synthesis of quinoline–chalcone hybrids from unactivated 4-alkylquinolines via aerobic oxidative sp³ C-H activation. The dual action of the iron catalyst enables both oxidative activation and aldol condensation, eliminating the need for the additional oxidants or strong bases that are required in the previously developed methods. This efficient access to quinoline–chalcone hybrids is anticipated to facilitate the development of anticancer agents based on this privileged scaffold. Furthermore, the synthetic versatility of the resulting hybrids is demonstrated through further functionalization and an application involving bioactive compounds.