Palladium-Catalyzed Weakly Coordinating Lactone-Directed C–H Bond Functionalization of 3-Arylcoumarins: Synthesis of Bioactive Coumestan Derivatives

Abstract

A palladium-catalyzed highly regioselective ortho-selective C–H functionalization of 3-arylcoumarins has been developed. The method utilizes the weakly coordinating lactone as a directing group. The versatility of the strategy is highlighted by developing methodologies for alkenylation, halogenation, fluoroalkoxylation, and hydroxylation. Different functional groups were well tolerated, and functionalized coumarins were obtained in moderate to high yields. The method also showed good selectivity for monofunctionalization versus difunctionalization. The generated ortho-hydroxy derivatives were cyclized in the presence of DDQ, thus developing a simple and fast method for the synthesis of bioactive coumestan from 3-arylcoumarins.