Difluorocarbene-Derived Trifluoromethylthiolation and [(18)F]Trifluoromethylthiolation of Aliphatic Electrophiles

Angew Chem Int Ed Engl. 2015 Nov 2;54(45):13236-40. doi: 10.1002/anie.201505446. Epub 2015 Sep 21.

Abstract

The first trifluoromethylthiolation and [(18)F]trifluoromethylthiolation of alkyl electrophiles with in situ generated difluorocarbene in the presence of elemental sulfur and external (radioactive) fluoride ion is described. This transition-metal-free approach is high yielding, compatible with a variety of functional groups, and operated under mild reaction conditions. The conceptual advantage of this exogenous-fluoride-mediated transformation enables unprecedented syntheses of [(18)F]CF3S-labeled molecules from most commonly used [(18)F]fluoride ions. The rapid radiochemical reaction time (≤1 min) and high functional-group tolerance allow access to a variety of aliphatic [(18)F]CF3S compounds in high yields.

Keywords: carbenes; fluorine; isotopic labeling; positron emission tomography; sulfur.

Publication types

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

MeSH terms

  • Fluorine / chemistry
  • Fluorine Radioisotopes / chemistry
  • Hydrocarbons, Fluorinated / chemical synthesis*
  • Hydrocarbons, Fluorinated / chemistry
  • Ions / chemistry
  • Molecular Structure
  • Sulfhydryl Compounds / chemical synthesis*
  • Sulfhydryl Compounds / chemistry
  • Sulfur / chemistry

Substances

  • Fluorine Radioisotopes
  • Hydrocarbons, Fluorinated
  • Ions
  • Sulfhydryl Compounds
  • difluorocarbene
  • Fluorine
  • Sulfur