Installation of -SO₂F groups onto primary amides

Abstract

A protocol of SO2F2-mediated installation of sulfonyl fluoride onto primary amides has been developed providing a new portal to sulfur(VI) fluoride exchange (SuFEx) click chemistry. The generated molecules contain pharmaceutically important amide and -SO2F moieties for application in the discovery of new therapeutics.

SuFEx Activation with Ca(NTf2)2: A Unified Strategy to Access Sulfamides, Sulfamates, and Sulfonamides from S(VI) Fluorides

“…Interest in sulfur­(VI) fluorides has grown immensely since Sharpless and co-workers introduced the concept of sulfur–fluoride exchange (SuFEx) chemistry in 2014. , For example, SuFEx has been applied extensively in chemical biology and medicinal chemistry with application toward protein labeling, protease inhibition, and drug target discovery . In polymer chemistry, sulfur­(VI) fluorides have been employed to generate novel polysulfates and polysulfonates, materials that have unique properties with promising applications. ,, Furthermore, advancements in fluorosulfurylation chemistry and the development of new reagents to install the −SO 2 F group have spurred additional exploration into these functional groups. − However, employment of sulfur­(VI) fluorides as synthetic precursors toward nitrogen-based sulfonylated compounds is underdeveloped. ,− …”

Transition-Metal-Free Disulfuration of Amides with Trisulfide Dioxides via Formation of Unaccessible S–S–N Bonds

“…210.3−210.8 °C, 1 H (400 MHz, CDCl 3 ) δ 7.68−7.61 (m, 2H), 7.60−7.52 (m, 3H), 1.39 (s, 9H). 13 N-(tert-Butyldisulfaneyl)-4-(trifluoromethyl)benzamide (3j). Flash column chromatography on silica gel (eluent: PE/EtOAc = 30/ 1, v/v) to afford 3j.…”

“…Analytical thin layer chromatography was carried out using silica gel GF254, visualized under UV light (at 254 nm). 1 H and 13 C{ 1 H} NMR spectra were recorded using a Bruker DRX-400 spectrometer with CDCl 3 and DMSO as solvents. The chemical shifts are referenced to signals at 7.26, 77.16, and 2.5, 39.6 ppm, respectively.…”

Sulfur(vi) fluorides as tools in biomolecular and medicinal chemistry

“…8c). 44 While sulfuryl fluoride is an effective reagent for sulfurylation, it poses notable health risks, 45 environmental hazards, 46 as well as the operational inconvenience that comes with working with toxic gases. However, it can be generated ex situ or a SO 2 F 2 surrogate can be employed.…”