Palladium-Catalyzed, Site-Selective C(sp2)8–H Halogenation and Nitration of 4-Quinolone Derivatives

Published in: J. Org. Chem. 2024, 89, 16, 11467–11479

Authors: Tapas Kumar Das (TCGLS Member), Prasanjit Ghosh, Shibaji Ghosh, Sajal Das

Abstract: Selective installation of halo and nitro groups in heterocyclic backbone through a transition-metal-catalyzed C–H bond activation strategy is immensely alluring to access high-value scaffolds. Here in, we disclosed N-pyrimidyl-directed assisted palladium(II)-catalyzed C(sp²)8–H halogenation and nitration of substituted 4-quinolone derivatives in the presence of N-halosuccinimide and tert-butyl nitrite, respectively, offering structurally diversified 8-halo/nitro-embedded 4-quinolone frameworks in high yields. Mechanistic studies indicated that the reaction follows an organometallic pathway with a reversible C–H metalation step. This operationally simple protocol is scalable with a broad substrate scope and excellent functional group compatibility. Moreover, the postdiversifications of the synthesized derivatives are also showcased to ensure the synthetic versatility of the methodology.

Grapical Abstract: