Nickel-catalyzed β-arylation and benzylation of 2'-hydroxychalcones to access warfarin analogues

镍催化2'-羟基查尔酮的β-芳基化和苄基化反应合成华法林类似物

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Abstract

The development of new methods for forming carbon-carbon bonds is essential for advancing the synthesis of biologically active molecules. Achieving high selectivity in these reactions remains a significant challenge in organic chemistry. Here we show that a nickel-catalyzed β-arylation and benzylation of 2'-hydroxychalcones enables the efficient synthesis of chalcone derivatives. This transformation is directed by the substrate's intrinsic hydroxy group, resulting in high chemoselectivity and avoiding unwanted byproducts. The resulting chalcone derivatives can be converted in one step into a series of 3-functionalized 4-hydroxycoumarin compounds. These compounds demonstrate excellent anticoagulant effects in animal studies, with some showing greater activity than the widely used drug warfarin. This approach offers a promising strategy for developing therapeutic agents and functional materials based on the chalcone structure.

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