Organic Letters 2012-08-03

Synthesis of α,α-difluoroethyl aryl and heteroaryl ethers.

Eddie Yang, Matthew R Reese, John M Humphrey

Index: Org. Lett. 14(15) , 3944-7, (2012)

Full Text: HTML

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.