10.1002/anie.201813761
Angewandte Chemie International Edition
COMMUNICATION
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Figure 2. A) MCF7 breast cancer cells and MCF10A breast cells were treated
for 72 h with 3i. Cell viability was assessed by an MTT assay; B) 3i was dosed
to breast normal (MCF10A) or cancer (MCF7) cells following 24 h of growth.
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In conclusion, we have developed an efficient and robust
bifluoride ion catalyzed SuFEx click chemistry protocol for the
synthesis of triflones, and previously underrepresented
bis(trifluoromethyl)sulfur oxyimines. The reactions are fast, high
yielding and proceed with low sub-stoichiometric quantities of
bifluoride catalyst KFHF. We propose a tentative mechanism
involving bifluoride activation of TMSCF3 to produce the
necessary “free” -CF3 anion, yielding a five-coordinate sulfur
intermediate that weakens the S-F bond allowing dissociation of
fluoride to reform the siliconate intermediate (7). With increasing
interest into methods for installing trifluoromethyl functionality into
drugs and drug candidates, we believe that the new SuFEx
protocol will find wide application in drug discovery, as exemplified
through the synthesis of the bis(trifluoromethyl)sulfur oxyimine
3i—a benzothiazole derived compound with selective cytotoxicity
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Acknowledgements
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The optimal conditions for the procedure were found to be: 1 eq. sulfonyl
fluoride, 1 eq. TMSCF3, 1 mol% KFHF in anhydrous DMSO for 30 min;
We thank the ARC for support through a Future Fellowship (JEM;
FT170100156), and the National Institutes of Health for financial
support (KBS; NIH R01GM117145).
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observed. Addition of excess TMSCF3 led to a complex and unidentified
mixture; b) The product 6n was found to be relatively unstable and slowly
decomposed.
Keywords: SuFEx • click chemistry • trifluoromethylation •
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