Electrophilic Reagents for the Direct Incorporation of Uncommon SCF2CF2H and SCF2CF3 Motifs

J Org Chem. 2022 Aug 19;87(16):10791-10806. doi: 10.1021/acs.joc.2c01038. Epub 2022 Aug 9.

Abstract

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 SCF3 and SCF2H moieties. Herein, two saccharin-based electrophilic reagents have been disclosed for the incorporation of uncommon SCF2CF2H and SCF2CF3 motifs. Their reactivity performance, multigram-scale preparation, and divergent derivatization have been thoroughly investigated with a variety of nucleophiles, including natural products and pharmaceuticals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products* / chemistry
  • Drug Discovery*
  • Indicators and Reagents

Substances

  • Biological Products
  • Indicators and Reagents