Versatile and mild HCl-catalyzed cationic imino Diels-Alder reaction for the synthesis of new tetrahydroquinoline derivatives

Abstract

<p>A simple, inexpensive, and mild one-pot methodology for the synthesis of novel 4-aryl-3-methyl-1,2,3,4-tetrahydroquinolines derivatives using aqueous HCl as catalyst has been developed. The key step involves the formal inverse-electron-demand [4π⁺ + 2π] cycloaddition reaction of in situ–generated cationic 2-azadienes with arylpropenes (isoeugenol and <i>trans</i>-anethole). Iminium ion intermediates are generated through the condensation between <i>N</i>-benzylanilines and formalin. The products are obtained with good to excellent yields and high <i>trans</i>-diastereoselectivity. Further catalytic hydrogenation (Pd/C) allowed debenzylation to successfully obtain the respective 4-aryl-3-methyl-<i>N</i>-H-tetrahydroquinolines of interest. Recent reports suggest that these compounds could serve as interesting models in pharmacological studies against parasites that cause the most common tropical diseases.</p