Beilstein Arch. 2026, 202612. https://doi.org/10.3762/bxiv.2026.12.v1
Published 30 Mar 2026
A novel intermolecular annulation protocol has been developed for the synthesis of quinoline-fused lactams by palladium-catalyzed sequential C–H/N–H functionalization of quinoline-2-carboxamides and 1,2-dihaloarenes. The reaction proceeds at the C–H bond on the quinoline adjacent to the amide group and at the amide N–H bond in the presence of 10 mol% Pd(OAc)2 in o-xylene as a solvent to afford the cyclized product in 34% yield. The yield increases to 81% when the reaction is carried out with 80 mol% P(4-MeOC6H4)3 as a ligand and with an increased catalyst loading of 20 mol%. The reaction affords lactams in up to 83% yield using amides containing various functional groups and substituted 1-bromo-2-iodobenzenes. Furthermore, 1,2-dibromo heteroarenes, such as benzothiophene and pyridine, undergo annulation to give the corresponding heterocycle-fused compounds. The high chemoselectivity of the 1,2-dihaloarene functional groups is confirmed in this reaction, thus enabling divergent synthesis of various multi-fused heterocyclic systems.
Keywords: C–H activation; C–N coupling; sequential reaction; chemodivergent synthesis; fused-ring system
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Sugita, S.; Okano, K.; Mori, A. Beilstein Arch. 2026, 202612. doi:10.3762/bxiv.2026.12.v1
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