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

ABSTRACT

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 trans-anethole). Iminium ion intermediates are generated through the condensation between N-benzylanilines and formalin. The products are obtained with good to excellent yields and high trans-diastereoselectivity. Further catalytic hydrogenation (Pd/C) allowed debenzylation to successfully obtain the respective 4-aryl-3-methyl-N-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.

GRAPHICAL ABSTRACT

KEYWORDS:

• Arylpropenes
• cationic imino Diels–Alder reaction
• hydrochloric acid
• tetrahydroquinolines

Acknowledgment

The authors would like to acknowledge Julia Bruno Colmenárez of the Instituto Venezolano de Investigaciones Científicas de Zulia, IVIC-Zulia (Maracaibo-Venezuela) for X-ray data collection.