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Analytical-scale synthesis of aryl-SF4Cl via flow microfluidic technology

Abstract

The SF5 group has great potential in influencing the drug-like features of organic molecules due to its chemical stability, hydrophobic surface, electron-withdrawing capability and unique octahedral geometry. However, the difficulty in synthesising SF5-containing compounds, particularly in aromatic systems, has impeded the widespread incorporation of this group into desired scaffolds in medicinal chemistry. The most troublesome step operationally involves the synthesis of the intermediate species ArSF4Cl from aryl-disulfides. Here, we report an analytical-scale synthesis of ArSF4Cl using flow microfluidic technology, allowing for safer handling of reagents and avoiding the need for gloveboxes or Cl2 cylinders. The system is fairly straightforward to prepare, clean to assemble and can be adapted easily to further developments. As well as making progress towards continuous de novo syntheses of ArSF5 compounds, this result broadly highlights the potential of flow chemistry in providing new avenues to perform challenging batch reactions.

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Acknowledgments

This work was supported financially by an Australian Government Research Training Program (RTP) Scholarship; and AINSE Limited through the Residential Student Scholarship (RSS). The National Imaging Facility is gratefully acknowledged. The authors also thank C.R. Pitts and A. Togni for helpful discussions.

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Correspondence to Glen Surjadinata or Giancarlo Pascali.

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Surjadinata, G., Hunter, L., Matesic, L. et al. Analytical-scale synthesis of aryl-SF4Cl via flow microfluidic technology. J Flow Chem 11, 107–115 (2021). https://doi.org/10.1007/s41981-020-00130-5

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Keywords

  • Pentafluorosulfanyl
  • Analytics
  • Flow chemistry
  • Fluorination
  • Arylsulfur chlorotetrafluoride