Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA.
Nat Chem. 2019 Oct;11(10):948-956. doi: 10.1038/s41557-019-0331-9. Epub 2019 Sep 23.
Difluorocarbene has important applications in pharmaceuticals, agrochemicals and materials, but all these applications proceed using just a few types of reaction by taking advantage of its intrinsic electrophilicity. Here, we report a palladium-catalysed strategy that confers the formed palladium difluorocarbene (Pd=CF) species with both nucleophilicity and electrophilicity by switching the valence state of the palladium centre (Pd(0) and Pd(II), respectively). Controllable catalytic difluorocarbene transfer occurs between readily available arylboronic acids and the difluorocarbene precursor diethyl bromodifluoromethylphosphonate (BrCFPO(OEt)). From just this simple fluorine source, difluorocarbene transfer enables access to four types of product: difluoromethylated and tetrafluoroethylated arenes and their corresponding fluoroalkylated ketones. The transfer can also be applied to the modification of pharmaceuticals and agrochemicals as well as the one-pot diversified synthesis of fluorinated compounds. Mechanistic and computational studies consistently reveal that competition between nucleophilic and electrophilic palladium difluorocarbene ([Pd]=CF) is the key factor controlling the catalytic difluorocarbene transfer.
二氟卡宾在药物、农化和材料领域有重要应用，但所有这些应用都只利用了其固有亲电性，通过几种特定的反应类型进行。在这里，我们报告了一种钯催化策略，通过改变钯中心的价态（分别为 Pd(0) 和 Pd(II)），使形成的钯二氟卡宾（Pd=CF）物种同时具有亲核性和亲电性。在这种可控的催化二氟卡宾转移反应中，可从易得的芳基硼酸和二氟溴代甲基膦酸二乙酯（BrCFPO(OEt))出发，发生二氟卡宾转移。仅从这种简单的氟源出发，就可实现四种类型产物的合成：二氟甲基化和全氟乙基化芳烃及其相应的氟烷基化酮。这种转移还可应用于药物和农化品的修饰，以及氟代化合物的一锅多样化合成。综合的实验和计算研究表明，亲核性和亲电性钯二氟卡宾([Pd]=CF)之间的竞争是控制催化二氟卡宾转移的关键因素。
