Unexpected Cascade Dehydrogenation Triggered by Pd/Cu-Catalyzed C(sp³)–H Arylation/Intramolecular C–N Coupling of Amides: Facile Access to 1,2-Dihydroquinolines

Abstract

In this work, we successfully explored an unexpected dehydrogenation triggered by Pd/Cu-catalyzed C(sp 3 )−H arylation and intramolecular C−N coupling of amides to synthesize the bioactive 1,2-dihydroquinoline scaffold with good regioselectivity and good compatibility of functional groups. This strategy provides an alternative route to realize molecular complexity and diversity from simple and readily available molecules via multiple C−H bond activation. Preliminary mechanistic studies demonstrated that β,γ-dehydrogenation is triggered by the arylation of the C(sp 3 )−H bond and the intramolecular C−N coupling.

Facile synthesis of chiral 2-functionalized tetrahydroquinolines via Pd/Cu-catalyzed cascade γ-C(sp3)–H arylation/C–N coupling of amides derived from amino acids and their derivatives

“…Encouragingly, the halo substituents chloro ( 2f ) or bromo ( 2g ), located para to the reaction position, which can be found in diverse transformations, are not disturbed in this reaction. These observations are consistent with our previous results, 17 indicating the good regioselectivity of this cascade reaction. Finally, other electron-withdrawing groups, cyano ( 2h ), methoxycarbonyl ( 2i ), and nitro ( 2j ), were able to give the corresponding products 4h (56%), 4i (58%), and 4j (62%), respectively.…”

“…16 We also have successfully developed the strategy of cascade reactions triggered by inert C(sp 3 )–H bond arylation to provide alternative access to the bioactive motifs 3,4-dihydroquinolin-2(1 H )-one and 1,2-dihydroquinoline. 17 While the application of this strategy in the chemical modification of AAs to prepare chiral THQs is still under development.…”