One-Pot, Three-Component Cascade Synthesis of 4-Amino Quinoline Derivatives from 2-Aminobenzonitriles, Aldehydes, and Active Methylene Compounds

A novel SnCl₄-mediated one-pot, three-component methodology has been developed for the direct synthesis of a diverse array of 4-aminoquinoline derivatives utilizing 2-aminobenzonitriles, aldehydes, and active methylene compounds. The reaction proceeds smoothly via a series of tandem reactions, including condensation followed by intramolecular cyclization and aromatization, to afford highly substituted 4-aminoquinolines in good to excellent yields (up to 88%) within 12-14 h. The protocol exhibits a broad substrate scope and excellent functional group tolerance. Notably, the strategy can also be applied for the construction of highly fused polycyclic frameworks through C-H activation and annulation and allows for the efficient synthesis of diacylated derivatives, highlighting its broad synthetic utility.