Dong Jinhuan, Shi Lou, Pan Ling, Xu Xianxiu, Liu Qun
Department of Chemistry and Jilin Province Key Laboratory of Organic Functional Molecular Design &Synthesis, Northeast Normal University, Changchun 130024, China.
Sci Rep. 2016 Jun 1;6:26957. doi: 10.1038/srep26957.
In recent years, numerous methods have emerged for the synthesis of trifluoromethylated arenes based on the late-stage introduction of a trifluoromethyl group onto an aryl ring. In sharp comparison, the synthesis of trifluoromethylated arenes based on the pre-introduction of a trifluoromethyl group onto an "aromatic to be" carbon has rarely been addressed. It has been found that 4-trifluoromethyl-p-quinol silyl ethers, the readily available and relatively stable compounds, can act as dielectrophiles to be applied to multi-component reactions for the synthesis of various trifluoromethylated arenes. Catalyzed by In(OTf)3, 4-trifluoromethyl-p-quinol silyl ethers react with C-, N-, and S-nucleophiles, respectively, in a regiospecific 1,2-addition manner to generate the corresponding highly reactive electrophilic intermediates. Further reaction of the in-situ generated electrophiles with a C-nucleophile followed by spontaneous aromatization enables the construction of functionalized trifluoromethyl arenes. This three-component, double nucleophilic addition/aromatization reaction based on the pre-introduction of a trifluoromethyl group onto an "aromatic to be" carbon provides a divergent strategy for the synthesis of trifluoromethylated arenes under mild reaction conditions in a single operation.
近年来,基于在芳环上后期引入三氟甲基,已出现了多种合成三氟甲基化芳烃的方法。与之形成鲜明对比的是,基于在“潜在芳烃”碳上预先引入三氟甲基来合成三氟甲基化芳烃的方法却很少被涉及。已发现4-三氟甲基对喹啉硅醚这种易于获得且相对稳定的化合物可作为亲双烯体应用于多组分反应,以合成各种三氟甲基化芳烃。在三氟甲磺酸铟(In(OTf)3)催化下,4-三氟甲基对喹啉硅醚分别与碳、氮和硫亲核试剂以区域特异性的1,2-加成方式反应,生成相应的高活性亲电中间体。原位生成的亲电试剂与碳亲核试剂进一步反应,随后自发芳构化,从而构建出功能化的三氟甲基芳烃。这种基于在“潜在芳烃”碳上预先引入三氟甲基的三组分双亲核加成/芳构化反应,为在温和反应条件下通过单一操作合成三氟甲基化芳烃提供了一种多样化的策略。