Synthesis of α,α-difluoroethyl aryl and heteroaryl ethers

Org Lett. 2012 Aug 3;14(15):3944-7. doi: 10.1021/ol301696x. Epub 2012 Jul 20.

Abstract

Fluorine plays a critical role in modern medicinal chemistry due to its unique properties, and new methods for its incorporation into target molecules are of high interest. An efficient new method for the preparation of aryl-α,α-difluoroethyl ethers (4) via addition of aryl and heteroaryl alcohols (1) to commercially available 2-bromo-1,1-difluoroethene (2) and subsequent hydrogenolysis is presented. This procedure is an attractive alternative to existing methods that employ harshly reactive fluorinating systems such as xenon difluoride and hydrogen fluoride.

MeSH terms

  • Alcohols / chemistry*
  • Catalysis
  • Combinatorial Chemistry Techniques
  • Ethers / chemical synthesis*
  • Ethers / chemistry
  • Fluorides / chemistry
  • Fluorine / chemistry*
  • Hydrocarbons, Fluorinated / chemical synthesis*
  • Hydrocarbons, Fluorinated / chemistry
  • Hydrofluoric Acid / chemistry
  • Molecular Structure
  • Xenon / chemistry

Substances

  • Alcohols
  • Ethers
  • Hydrocarbons, Fluorinated
  • Fluorine
  • Xenon
  • xenon fluoride
  • Fluorides
  • Hydrofluoric Acid