Herein, we developed a practical method for the direct cross-coupling of ethyl 3-bromo-3-alkyl-2,2-difluoropropanoates with coumarins/quinolinones, leveraging a halogen bond as the pivotal non-covalent interaction. Employing this protocol, a library of structurally diverse difluoroalkylated coumarin and quinolinone derivatives has been successfully synthesized under mild reaction conditions, affording moderate to good yields. Notably, compound 3l demonstrated potent antitumor efficacy against both Huh-7 and A549 cancer cell lines, with IC₅₀ values of 4.6 μM and 6.8 μM, respectively.

中文翻译：

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卤素键促进的 3-溴-3-烷基-2,2-二氟丙酸乙酯与香豆素/喹啉酮的直接交叉偶联

在此，我们开发了一种实用方法，利用卤素键作为关键的非共价相互作用，将 3-溴-3-烷基-2,2-二氟丙酸乙酯与香豆素/喹啉酮直接交叉偶联。采用该方案，在温和的反应条件下成功合成了结构多样的二氟烷基化香豆素和喹啉酮衍生物库，并提供了中等至良好的产率。值得注意的是，化合物3l对Huh-7和A549癌细胞系均表现出有效的抗肿瘤功效，IC ₅₀值分别为4.6 μM和6.8 μM。