A Review on Indoles Synthesis from Nitroarenes: Classical to Modern Approaches

Abstract

Indole is a highly privileged and versatile heterocyclic pharmacophore crucial in natural product synthesis, drug discovery, pharmaceuticals, and medicinal chemistry. This review provides a comprehensive analysis of various synthetic approaches to indole with a particular emphasis on nitroarenes as key precursors. Despite the vast exploration of indoles and their derivatives in natural and pharmacological applications due to their significant bioactivity, several established synthetic methodologies remain underexplored. Traditionally, indole synthesis from ortho-substituted nitroarenes has been achieved through methods such as Bartoli, Reissert, Cadogan, and Leimgruber–Batcho, etc. approaches. However, recent advancements have introduced novel one-pot and tandem strategies that effectively integrate redox and hydrogenation reactions to streamline indole formation. Additionally, emerging photochemical and electrochemical techniques have facilitated the selective synthesis of nitroarenes, allowing access to indoles with precisely tailored 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.