A review on indole synthesis from nitroarenes: classical to modern approaches

Abstract

Indoles are highly privileged and versatile heterocyclic pharmacophores that play a crucial role in natural product synthesis, drug discovery, pharmaceuticals, and medicinal chemistry. This review provides a comprehensive analysis of various synthetic approaches to indoles with a particular emphasis on nitroarenes as key precursors. Although indoles and their derivatives have been extensively explored for their bioactivity in natural and pharmacological contexts, several classical synthetic methodologies remain underutilized. Traditionally, indole synthesis from ortho-substituted nitroarenes has been achieved through methods such as Bartoli, Reissert, Cadogan, and Leimgruber–Batcho approaches. However, recent advancements have introduced novel one-pot and tandem strategies that effectively integrate redox and hydrogenation reactions to streamline indole formation. Emerging photochemical and electrochemical techniques have also enabled the selective conversion of nitroarenes into indoles bearing well-defined functional groups. Beyond their intrinsic biological activity, indoles serve as valuable intermediates for further derivatization into compounds such as isatins and oxindoles, expanding their synthetic potential. These advancements continue to enhance the synthetic toolkit for constructing biologically active indoles, with far-reaching applications in pharmaceuticals, agrochemicals, and advanced materials.