Relatively low reactivity hinders using chlorodifluoromethane (ClCF₂H) for general difluoromethylation with organic molecules, despite its availability as an inexpensive industrial chemical. To date, transformations of ClCF₂H are very limited and most of them involve difluorocarbene intermediate. Here, we describe a strategy for difluoromethylation of aromatics through nickel-catalyzed cross-coupling of ClCF₂H with readily accessible (hetero)aryl chlorides. The reaction proceeds under mild reaction conditions with high efficiency and features synthetic simplicity without preformation of arylmetals and broad substrate scope, including a variety of heteroaromatics and commercially available pharmaceuticals. The reliable practicability and scalability of the current nickel-catalyzed process has also been demonstrated by several 10-g scale reactions without loss of reaction efficiency. Preliminary mechanistic studies reveal that the reaction starts from the oxidative addition of aryl chlorides to Ni(0) and a difluoromethyl radical is involved in the reaction, providing a route for applications of ClCF₂H in organic synthesis and related chemistry.

中文翻译：

---

镍催化的（杂）芳基氯与氯二氟甲烷的二氟甲基化。

相对较低的反应性阻碍了使用氯二氟甲烷（ClCF ₂ H）与有机分子进行一般的二氟甲基化，尽管它可以作为廉价的工业化学品获得。迄今为止，ClCF ₂ H的转化非常有限，并且大多数涉及二氟卡宾中间体。在这里，我们描述了一种通过镍催化的ClCF ₂交叉偶联来实现芳族化合物二氟甲基化的策略。H与容易获得的（杂）芳基氯化物。该反应在温和的反应条件下高效进行，并且具有合成简便性，无需形成芳基金属和宽范围的底物范围，包括各种杂芳族化合物和可商购的药物。当前的镍催化工艺的可靠实用性和可扩展性也已经通过数个10克规模的反应证明，而不会损失反应效率。初步的机理研究表明，该反应从芳基氯化物的氧化加成到Ni（0）开始，并且该反应涉及二氟甲基，从而为ClCF ₂ H在有机合成和相关化学中的应用提供了途径。