Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides

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(...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie International Edition 2019-03, Vol.58 (14), p.4552-4556
Main Authors: Smedley, Christopher J., Zheng, Qinheng, Gao, Bing, Li, Suhua, Molino, Andrew, Duivenvoorden, Hendrika M., Parker, Belinda S., Wilson, David J. D., Sharpless, K. Barry, Moses, John E.
Format: Article
Language:English
Subjects:
Anticancer properties
bis(trifluoromethyl)sulfur oxyimines
Chemical synthesis
click chemistry
Fluorides
fluorine
Nucleophiles
Organic chemistry
Potassium
Purification
Substrates
SuFEx chemistry
Sulfur
trifluoromethylation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. An expedient SuFEx trifluoromethylation of sulfonyl fluorides and iminosulfur oxyfluorides is described. The efficient S−F exchange with TMSCF3 is initiated by sub‐stoichiometric quantities of bifluoride ion [FHF]− in anhydrous DMSO. The selective anticancer properties of previously inaccessible bis(trifluoromethyl)sulfur oxyimines are also demonstrated.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201813761