A Heck-Matsuda Process for the Synthesis of β-Arylethenesulfonyl Fluorides: Selectively Addressable Bis-electrophiles for SuFEx Click Chemistry

Angew Chem Int Ed Engl. 2016 Nov 2;55(45):14155-14158. doi: 10.1002/anie.201608807. Epub 2016 Oct 10.

Abstract

A Heck-Matsuda process for the synthesis of the otherwise difficult to access compounds, β-arylethenesulfonyl fluorides, is described. Ethenesulfonyl fluoride (i.e., vinylsulfonyl fluoride, or ESF) undergoes β-arylation with stable and readily prepared arenediazonium tetrafluoroborates in the presence of the catalyst palladium(II) acetate to afford the E-isomer sulfonyl analogues of cinnamoyl fluoride in 43-97 % yield. The β-arylethenesulfonyl fluorides are found to be selectively addressable bis-electrophiles for sulfur(VI) fluoride exchange (SuFEx) click chemistry, in which either the alkenyl moiety or the sulfonyl fluoride group can be the exclusive site of nucleophilic attack under defined conditions, making these rather simple cores attractive for covalent drug discovery.

Keywords: Heck-Matsuda reaction; Michael addition; ethenesulfonyl fluoride; sulfur(VI) fluoride exchange (SuFEx); β-arylethenesulfonyl fluorides.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Click Chemistry
  • Ethylenes / chemical synthesis*
  • Ethylenes / chemistry
  • Molecular Structure
  • Sulfinic Acids / chemical synthesis*
  • Sulfinic Acids / chemistry

Substances

  • Ethylenes
  • Sulfinic Acids
  • sulfuryl fluoride
  • ethylene