Fe‐Catalyzed, Solvent‐Controlled, Switchable Routes for the Domino Construction of 2,4‐Disubstituted and 4‐Substituted Quinoline Scaffolds

Abstract

In this report, we unveil a highly efficient novel protocol for the domino synthesis of 2,4‐disubstituted and 4‐substituted quinoline scaffolds. The developed strategy involves earth‐abundant Fe‐catalyzed, solvent‐controlled, switchable routes for the selective construction of 2,4‐disubstituted and 4‐substituted quinoline frameworks, achieved by using either trifluoroethanol (TFE) or methanol (MeOH) as a solvent. By employing TFE as a solvent in Path A, the alkyne itself serves as a dual synthon through Fe‐catalyzed in situ C(sp)‐C(sp) bond cleavage, enabling the synthesis of two important molecules: 2,4‐disubstituted and 4‐substituted quinolines. Later, upon switching the reaction medium from TFE to MeOH for Path‐B, only 4‐substituted quinolines were obtained extensively. In this Path‐B, Fe‐catalyzed oxidation of methanol was observed and here methanol functioned as both a solvent and an environmentally benign carbon source. Both of these strategies were utilized to prepare a broad range of mono‐ and di‐substituted quinoline derivatives. In the application section and for practical utility, the scale‐up studies, along with the photophysical properties of the synthesized quinoline moiety are also demonstrated.