Palladium-Catalyzed C−F Activation of Polyfluoronitrobenzene Derivatives in Suzuki−Miyaura Coupling Reactions

Highly fluorinated nitrobenzene derivatives are suitable substrates for palladium-catalyzed C−F bond arylation using readily available palladium catalysts under both conventional heating and microwave conditions. Arylation occurs ortho to the nitro group offering a synthetic route to polyfluorinated 2-arylnitrobenzene systems. The regiochemistry of the arylation reactions suggests that there is a significant directing interaction between the nitro group and the incoming nucleophilic palladium catalyst which is facilitated by the presence of several fluorine atoms attached the ring. Investigations into the regioselectivity and reactivity of several tetrafluoro- and trifluoronitrobenzene derivatives provides further evidence for the highly nucleophilic character of the oxidative addition step in contrast to the concerted mechanism of more conventional Suzuki−Miyaura coupling reactions involving aryl iodides and bromides.

高氟化硝基苯衍生物是钯催化C-F键芳基化反应的适宜底物，该反应可使用易得的钯催化剂，在常规加热及微波辐照条件下均可进行。芳基化反应发生于硝基的邻位，为多氟化2-芳基硝基苯体系提供了合成路径。该芳基化反应的区域化学特征表明，硝基与进攻性亲核钯催化剂之间存在显著的导向作用，苯环上的多个氟原子可促进这一作用。针对多种四氟硝基苯及三氟硝基苯衍生物的区域选择性与反应活性开展的研究，进一步证实了氧化加成步骤具有高度亲核性——这与涉及芳基碘化物与溴化物的传统铃木-宫浦（Suzuki−Miyaura）偶联反应的协同机制截然不同。