Divergent Continuous-Flow Synthesis of Flavones and Aurones via CO-Mediated Carbonylation

Carbonylation reactions are fundamental to organic and industrial chemistry, providing efficient access to carbonyl-containing compounds through the incorporation of carbon monoxide (CO) [1]. Despite its low cost and excellent atom economy, the use of CO in conventional batch processes is limited by its toxicity, high-pressure conditions, and storage. Continuous flow chemistry has emerged as a powerful alternative, improving safer handling of the gas [2]. Flavones and aurones are structurally related oxygen-containing heterocycles within the flavonoid family, widely found in bioactive natural products with antioxidant, anti-inflammatory, and anticancer properties. Despite close structural similarity, selective synthesis of either scaffold remains a challenge [3, 4]. Here, we report a palladium-catalyzed carbonylation under flow conditions to allow selective access to either flavones or aurones by fine-tuning reaction parameters, specifically base and solvent (Figure 1). The transformation proceeds efficiently at 100 °C and 5 bar of CO pressure, affording good yields and broad functional-group tolerance. The protocol is scalable and industrially relevant, displaying potential applicability to the synthesis of commercial drugs, natural products, and deuterium-labelled compounds. Moreover, E/Z-selective synthesis of aurones was achieved on a model substrate, and ongoing investigations into in-continuous E/Z photoisomerization aim to further expand the utility of aurones as biological probes.