Fe(III)-Mediated Oxidative [5 + 1] Cyclization for the Highly Site-Selective Synthesis of Functionalized Quinoline Derivatives

Abstract

We describe a method for the construction of highly functionalized quinoline derivatives from enaminones via an oxidative [5 + 1] cyclization. A plausible mechanism may involve a cascade sequence including single-electron transfer (SET), radical Michael addition, elimination of ArNH2, a second Michael addition, keto–enol tautomerism, inverse aldol reaction, intramolecular cyclization, and aromatization. Remarkably, this multistep transformation was accomplished in a single operation simply by heating a mixture of the enaminone substrate, [BMIM]PF6, and FeCl3, which served as both the oxidant and Lewis acid promoter. As a result, a broad range of quinoline derivatives was obtained through an efficient oxidative cascade involving the cleavage of one C═C bond and one C–N bond, as well as the formation of two new bonds, one C═C bond, and one C–C bond, in a single step. This method provides a practical route to highly functionalized quinoline derivatives suitable for combinatorial and parallel synthesis of complex natural-product-like scaffolds, while avoiding tedious multistep procedures.