Abstract
Flavones are an important class of building blocks for numerous biologically active molecules, pharmaceuticals, and natural products. Reductive carbonylation of CO(2) is a powerful method to provide high-value heterocycles quickly. However, examples of transition metal-catalyzed carbonylation to produce flavones using CO(2) are quite scarce, and the related copper-catalyzed carbonylative cyclization of CO(2) is not reported. Here, a general procedure is developed for the copper-catalyzed carbonylative C(sp(3))-H bond synthesis of flavone using CO(2) as the C1 source. Additionally, (13)C-labeled flavones are successfully synthesized using [(13)C]-CO(2), demonstrating significant inhibitor activity against MCF-7 cells in antitumor assays. Mechanistic investigations suggest that the phenolic group accelerates CO(2) mass transfer by promoting nucleophilic addition to DBU-CO(2) complexes, followed by selective intramolecular carbonylative cyclization.