Huertas.Morales, IvánCendón, BorjaCosta, DomingoGulías Costa, Moisés2024-10-252024-10-252024Huertas-Morales, I.; Cendón, B.; Costa, D.; Mascareñas, J. L.; Gulías, M. (2024), Assembly of 2-substituted tetrahydroquinolines from ortho-methylbenzenesulfamides and dienes, using a C(sp3)-H activation/ annulation sequence. Org. Lett., 26: 7789–7794. doi: 10.1021/acs.orglett.4c02292https://hdl.handle.net/10347/37554This is the peer reviewed version of the following article: Huertas-Morales, I.; Cendón, B.; Costa, D.; Mascareñas, J. L.; Gulías, M. (2024), Assembly of 2-substituted tetrahydroquinolines from ortho-methylbenzenesulfamides and dienes, using a C(sp3)-H activation/ annulation sequence. Org. Lett., 26: 7789–7794, which has been published in final form at https://doi.org/10.1021/acs.orglett.4c02292. This article may be used for non-commercial purposes in accordance with ACS Terms and Conditions for Use of SelfArchived Versions.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.engjournal article10.1021/acs.orglett.4c022921523-7052open access