Ru(ii) catalyzed chelation assisted C(sp2)–H bond functionalization along with concomitant (4 + 2) annulation

Abstract

Efficacious protocols have been established to synthesize a structurally privileged Π-extended coumarin-fused pyridone nucleus by activating the vinylic C(sp²)–H bond of coumarin-3-carboxamide under the influence of inexpensive Ru(II)-metal. Here an N-methoxy carboxamide entity has been exploited as the chelating fragment to manifest C(sp²)–H bond functionalization with a concomitant (4 + 2) annulation reaction, resulting in heterocyclic ring-forming protocols along with sulfoxonium ylide and iodonium ylide as representative bench-stable carbene surrogates. This diverse heterocycle formation via carbene insertion strategies, is further expanded to activate the ortho-C(sp²)–H bonds of different heterocycles by employing the sp²-N moiety as the directing group to develop acyl-alkylated/alkenylated quinazolines, isoxazoles and highly fluorescent pyridone-N-oxides. Intriguingly, during an evaluation of the versatility of the current protocols, a one-pot double C–H activation has been rationalized in the presence of iodonium ylide, which results in biologically potent benzimidazole-fused coumarin-centered bridge-headed polycyclic heteroarenes. Furthermore, a chemo-selective late-stage synthetic transformation is being designed to develop differently substituted pyridone analogues by switching the nature of the reducing agent. In addition, a photophysical experiment was done on one pyridine-N-oxide compound (7e) and delightfully it exhibited fluorescence quenching activity selectively in the presence of Al³⁺ ions, which appears to be a unique feature of our methodology. Finally, upon correlation of the merit of the developed pathways, the iodonium ylide mediated strategy appears to be superior.