Skeletal Editing of Anthranils for Chemodivergent Synthesis

Abstract

Herein, we report an acid-catalysed skeletal editing platform for direct conversion of anthranils into diverse nitrogen-rich heterocycles. Central to this method is the generation of nitroso imine intermediate via an acid-mediated amine addition, ring-opening and aerobic oxidation sequence. This sustainable route further enables amine-dependent chemodivergent tandem cyclizations to deliver structurally distinct products. With aromatic or aliphatic amines, the reaction achieves a formal hybrid skeletal editing/C–H amination of anthranils, yielding 3-amino-2H-indazoles. Employing benzylamines redirects the pathway to 4-aminoquinazolines by leveraging the acidity of the benzylic C(sp3)–H bond, while diamine or amino alcohol substrates enable divergent synthesis of benzimidazoles and 2-aminobenzamides. This protocol features sustainable synthesis of pharmaceutically relevant scaffolds with high atom economy in renewable EtOH solvent, catalysed by earth-abundant metal.