Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides

Christopher J. Smedley, Qinheng Zheng, Bing Gao, Suhua Li, Andrew Molino, Hendrika M. Duivenvoorden, Belinda S. Parker, David J.D. Wilson, K. Barry Sharpless, John E. Moses

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12 Citations (Scopus)

Abstract

SuFEx is a new-generation click chemistry transformation that exploits the unique properties of S−F bonds and their ability to undergo near-perfect reactions with nucleophiles. We report here the first SuFEx-based procedure for the efficient synthesis of pharmaceutically important triflones and bis(trifluoromethyl)sulfur oxyimines from sulfonyl fluorides and iminosulfur oxydifluorides, respectively. The new process involves rapid S−F exchange with trifluoromethyltrimethylsilane (TMSCF3) upon activation by potassium bifluoride in anhydrous DMSO. The reaction tolerates a wide selection of substrates and proceeds under mild conditions without need for chromatographic purification. A tentative mechanism is proposed involving nucleophilic displacement of S−F by the trifluoromethyl anion via a five-coordinate intermediate. The utility of late-stage SuFEx trifluoromethylation is demonstrated through the synthesis and selective anticancer properties of a bis(trifluoromethyl)sulfur oxyimine.

Original languageEnglish
Pages (from-to)4552-4556
Number of pages5
JournalAngewandte Chemie - International Edition
Volume58
Issue number14
DOIs
Publication statusPublished - 26 Mar 2019
Externally publishedYes

Keywords

  • bis(trifluoromethyl)sulfur oxyimines
  • click chemistry
  • fluorine
  • SuFEx chemistry
  • trifluoromethylation

Cite this

Smedley, C. J., Zheng, Q., Gao, B., Li, S., Molino, A., Duivenvoorden, H. M., Parker, B. S., Wilson, D. J. D., Sharpless, K. B., & Moses, J. E. (2019). Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides. Angewandte Chemie - International Edition, 58(14), 4552-4556. https://doi.org/10.1002/anie.201813761