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Asymmetric silver-catalysed intermolecular bromotrifluoromethoxylation of alkenes with a new trifluoromethoxylation reagent

Nature Chemistry volume 9, pages 546–551 (2017)Cite this article

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Abstract

Fluorinated organic compounds are becoming increasingly important in pharmaceuticals, agrochemicals and materials science. The introduction of trifluoromethoxy groups into new drugs and agrochemicals has attracted much attention due to their strongly electron-withdrawing nature and high lipophilicity. However, synthesis of trifluoromethoxylated organic molecules is difficult owing to the decomposition of trifluoromethoxide anion and β-fluoride elimination from transition-metal–trifluoromethoxide complexes, and no catalytic enantioselective trifluoromethoxylation reaction has been reported until now. Here, we present an example of an asymmetric silver-catalysed intermolecular bromotrifluoromethoxylation of alkenes with trifluoromethyl arylsulfonate (TFMS) as a new trifluoromethoxylation reagent. Compared to other trifluoromethoxylation reagents, TFMS is easily prepared and thermally stable with good reactivity. In addition, this reaction is operationally simple, scalable and proceeds under mild reaction conditions. Furthermore, broad scope and good functional group compatibility has been demonstrated by application of the method to the bromotrifluoromethoxylation of double bonds in natural products and natural product derivatives.

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Figure 1: Trifluoromethyl aryl sulfonate (TFMS) as a new trifluoromethoxylation reagent.
Figure 2: Insights into the reaction mechanism of asymmetric silver-catalysed intermolecular bromotrifluoromethoxylation of alkenes.

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Acknowledgements

The authors dedicate this manuscript to Qi-lin Zhou on the occasion of his sixtieth birthday. We are grateful for financial support from the State Key Laboratory of Elemento-Organic Chemistry, the National Key Research and Development Program of China (2016YFA0602900) and NFSC (21402098, 21421062, 21522205).

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Authors and Affiliations

  1. State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, China

    Shuo Guo, Fei Cong, Rui Guo, Liang Wang & Pingping Tang

  2. Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, 300071, China

    Pingping Tang

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  1. Shuo Guo
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  2. Fei Cong
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Contributions

S.G., F.C., R.G. and L.W. performed the experiments and analysed the data. P.T. designed and directed the project. P.T. wrote the manuscript. All of the authors discussed the results and commented on the manuscript.

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Correspondence to Pingping Tang.

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The authors declare no competing financial interests.

Supplementary information

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Supplementary information (PDF 8374 kb)

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Crystallographic data for compound 3i. (CIF 213 kb)

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Crystallographic data for compound 3t. (CIF 661 kb)

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Crystallographic data for compound 3x. (CIF 394 kb)

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Crystallographic data for compound 5a. (CIF 256 kb)

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Crystallographic data for compound 5b. (CIF 643 kb)

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Guo, S., Cong, F., Guo, R. et al. Asymmetric silver-catalysed intermolecular bromotrifluoromethoxylation of alkenes with a new trifluoromethoxylation reagent. Nature Chem 9, 546–551 (2017). https://doi.org/10.1038/nchem.2711

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