Copper-Catalyzed Carbonylative Cyclization of CO2: A Promising Approach for Synthesis of Flavone

Abstract

Flavones are an important class of building blocks for numerous biologically active molecules, pharmaceuticals, and natural products. Reductive carbonylation of CO2 is a powerful method to provide high-value heterocycles quickly. However, examples of transition metal-catalyzed carbonylation to produce flavones using CO2 are quite scarce, and the related copper-catalyzed carbonylative cyclization of CO2 is not reported. Here, a general procedure is developed for the copper-catalyzed carbonylative C(sp3)-H bond synthesis of flavone using CO2 as the C1 source. Additionally, 13C-labeled flavones are successfully synthesized using [13C]-CO2, demonstrating significant inhibitor activity against MCF-7 cells in antitumor assays. Mechanistic investigations suggest that the phenolic group accelerates CO2 mass transfer by promoting nucleophilic addition to DBU-CO2 complexes, followed by selective intramolecular carbonylative cyclization.