These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
2 files

Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides

revised on 04.12.2018, 01:10 and posted on 04.12.2018, 13:40 by Christopher J. Smedley, Bing Gao, Suhua Li, Qinheng Zheng, Andrew Molino, Hendrika M. Duivenvoorden, Belinda S. Parker, David J. D. Wilson, K. Barry Sharpless, John E. Moses
Sulfur-Fluoride Exchange (SuFEx) is the new generation click chemistry transformation exploiting the unique properties of S-F bonds and their ability to undergo near-perfect reactions with nucleophiles. We report here the first SuFEx based protocol for the efficient synthesis of pharmaceutically important triflones and bis(trifluoromethyl)sulfur oxyimines from the corresponding sulfonyl fluorides and iminosulfur oxydifluorides, respectively. The new protocol involves the rapid exchange of the S-F bond with trifluoromethyltrimethylsilane (TMSCF3) upon activation with 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 catalytic mechanism is proposed supported by DFT calculations, involving formation of the free trifluoromethyl anion followed by nucleophilic displacement of the S-F through a five-coordinate intermediate. The preparation of a benzothiazole derived bis(trifluoromethyl)sulfur oxyimine with cytotoxic selectivity for MCF7 breast cancer cells demonstrates the utility of this methodology for the late-stage functionalization of bioactive molecules.


Developing next generation click chemistry

Australian Research Council

Find out more...

Sulfur(VI) Fluoride Exchange (SuFEx): new developments and biological applications

National Institute of General Medical Sciences

Find out more...


Email Address of Submitting Author


La Trobe University



ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest