Catalytic SuFEx reactivity of sulfonimidoyl fluorides with functionalized amines with automation applicable conditions
Author(s)
Type
Journal Article
Abstract
Sulfonimidamides have emerged as attractive chemical motifs in drug discovery and as sulfonamide bioisosteres that can offer improved pharmacokinetic and physiochemical properties. Herein, a mild sulfur(VI) fluorine exchange (SuFEx) reaction of sulfonimidoyl fluorides using HOBt as a nucleophilic catalyst is reported that is applicable to automated array technologies. A diverse set of sulfonimidamides is prepared with functionalized amines and sulfonimidoyl fluorides, with variation in carbon and nitrogen-substituents. Moreover, the discovery and utilization of SNAr reactivity of a fluoroaryl-sulfonimidoyl fluoride under modified conditions, occurring in the presence of the sulfonimidoyl fluoride functionality, allow for the divergent generation of sulfonimidoyl fluoride reagents. Orthogonal SNAr or SuFEx processes are achieved highly chemoselectively, as well as sequentially in one-pot. A further 24-compound array is generated using an automated reaction set-up and purification.
Date Issued
2025-11-11
Date Acceptance
2025-06-26
Citation
ChemistryEurope, 2025, 3 (6)
ISSN
2751-4765
Publisher
Wiley
Journal / Book Title
ChemistryEurope
Volume
3
Issue
6
Copyright Statement
© 2025 The Author(s). ChemistryEurope published by Chemistry Europe and Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Publication Status
Published
Article Number
ARTN e202500163
Date Publish Online
2025-07-09