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Updated: Jun 13, 2025

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Assembly of 2-Substituted Tetrahydroquinolines from ortho-Methylbenzenesulfamides and Dienes, Using a C(sp3)-H
Iván Huertas-Morales1, Borja Cendón1, Domingo Costa1
1Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS) and Departamento de Química Orgánica, Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain.
Abstract:
1,2,3,4-Tetrahydroquinolines (THQs) are essential structural cores in many natural products and pharmaceutical drugs. Especially relevant are those presenting substitutions at position 2, yet practical methods for their one-step assembly from acyclic precursors are very scarce. Herein, we present a straightforward approach to assembling these skeletons from ortho-methylanilines using a palladium-catalyzed C(sp3)-H activation/formal cycloaddition sequence. Key for the success of the approach is the use of dienes as partners, since they lead to stable π-allyl palladium intermediates that prevent β-hydride elimination processes and allow installation of versatile alkenyl handles at position 2. Moreover, installing a perfluorobenzenesulfonyl substituent at the amine not only facilitates the C-H activation but also allows for an easy recovery of the free amine.
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