Continuous flow palladium-catalyzed trifluoromethylthiolation of C-H bonds

Abstract

A continuous flow process for the synthesis of trifluoromethylthioethers is reported. The palladium-catalyzed C-H trifluoromethylthiolation of amides derived from the 8-aminoquinoline using N-[(trifluoromethyl)thio]phthalimide produced the desired products in moderate to good yields with a residence time of 20 min. In comparison with the batch process, the reaction time was decreased by a factor of 100 to 200, demonstrating the positive effect of continuous flow processes for this type of reaction.

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Acknowledgments

This research was supported by the Natural Science and Engineering Research Council of Canada (NSERC) under the CREATE Training Program in Continuous Flow Science, a discovery grant from NSERC (Canada), the Canada Foundation for Innovation, the Université de Montréal and the Centre in Green Chemistry and Catalysis (CGCC). We would like to thank Alexandra Furtos from the Regional Mass Spectrometry Centre and Sylvie Bilodeau from the Regional Centre of NMR spectroscopy of the Université de Montréal. H.-Y.X. thanks CSC for fellowship.

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Correspondence to Tatiana Besset or Hélène Lebel.

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Bouchard, A., Kairouz, V., Manneveau, M. et al. Continuous flow palladium-catalyzed trifluoromethylthiolation of C-H bonds. J Flow Chem 9, 9–12 (2019). https://doi.org/10.1007/s41981-018-0023-4

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Keywords

  • Aminoquinoline
  • Bidentate directing group
  • C-SCF3 bond
  • Organofluorine compounds
  • Flow process
  • C-H activation
  • Halogenation
  • Trifluoromethylthioethers