Electrophilic Reagents for the Direct Incorporation of Uncommon SCFCFH and SCFCF Motifs.

The introduction of fluoroalkylthioether groups has attracted the attention of the drug-discovery community given the special physicochemical and pharmacokinetic features they confer to bioactive compounds, yet these are often limited to standard SCF and SCFH moieties. Herein, two saccharin-based electrophilic reagents have been disclosed for the incorporation of uncommon SCFCFH and SCFCF motifs. Their reactivity performance, multigram-scale preparation, and divergent derivatization have been thoroughly investigated with a variety of nucleophiles, including natural products and pharmaceuticals.