Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides

Smedley, Christopher, Gao, Bing, Li, Suhua, Zheng, Qinheng, Molino, Andrew, Duivenvoorden, Hendrika, Parker, Belinda, Wilson, David, Sharpless, Barry, Moses, John (December 2018) Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides. ChemRxiv. (Unpublished)

[thumbnail of 2018.Smedley. Bifluoride.pdf] PDF
2018.Smedley. Bifluoride.pdf
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (824kB)
DOI: 10.26434/chemrxiv.7312595.v3


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.

Item Type: Paper
Subjects: chemistry > techniques > click chemistry > Accelerated SuFEx Click Chemistry
CSHL Authors:
Communities: CSHL labs > Moses lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 4 December 2018
Date Deposited: 25 May 2022 16:53
Last Modified: 25 May 2022 16:53

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving