Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides

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. (March 2019) Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides. Angew Chem Int Ed Engl, 58 (14). pp. 4552-4556. ISSN 1433-7851

DOI: 10.1002/anie.201813761


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 (TMSCF(3) ) 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.

Item Type: Paper
Additional Information: Angewandte Chemie (International ed. in English)
Uncontrolled Keywords: *SuFEx chemistry *bis(trifluoromethyl)sulfur oxyimines *click chemistry *fluorine *trifluoromethylation
Subjects: chemistry
chemistry > techniques > click chemistry
chemistry > techniques
CSHL Authors:
Communities: CSHL labs > Moses lab
Depositing User: Matthew Dunn
Date: 26 March 2019
Date Deposited: 08 Jan 2021 17:14
Last Modified: 02 Feb 2024 20:52
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