Xie Qiqiang, Zhu Ziyue, Li Lingchun, Ni Chuanfa, Hu Jinbo
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, 345 Ling-Ling Road, Shanghai, 200032, China.
Angew Chem Int Ed Engl. 2019 May 6;58(19):6405-6410. doi: 10.1002/anie.201900763. Epub 2019 Apr 5.
An efficient method for the selective C-difluoromethylation of carbon acids with the reagent TMSCF Br has been developed. A variety of structurally diverse sp - and sp-hybridized carbon nucleophiles, including esters, amides, fluorenes, terminal alkynes, β-ketoesters, malonates, and other activated C-H nucleophiles, could be efficiently and selectively transformed into the corresponding C-difluoromethylated products under mild conditions. This protocol is also effective for the late-stage difluoromethylation of pharmaceutically relevant molecules and can be readily scaled up. Moreover, ambident substrates with more than one reactive site towards difluorocarbene can be difluoromethylated orthogonally using TMSCF Br.
已开发出一种使用试剂TMSCF₂Br对碳酸进行选择性C-二氟甲基化的有效方法。多种结构多样的sp²-和sp-杂化碳亲核试剂，包括酯、酰胺、芴、末端炔烃、β-酮酯、丙二酸酯和其他活化的C-H亲核试剂，可在温和条件下高效且选择性地转化为相应的C-二氟甲基化产物。该方案对于药物相关分子的后期二氟甲基化也有效，并且可以很容易地扩大规模。此外，对二氟卡宾有多个反应位点的双亲性底物可以使用TMSCF₂Br进行正交二氟甲基化。
