Organic synthesis in fluoroalcohol-water two-phase systems

Abstract

The addition of organic reactants to aqueous solutions of hexafluoroisopropanol (HFIP) leads to the formation of a two-phase system with one phase enriched in HFIP and the organic reactant and another largely aqueous phase. These systems were used as a reaction medium for Friedel–Crafts reactions between arenes and heteroarenes with a benzyl chloride electrophile. Good to excellent yields were obtained for nucleophiles of varying strength in the presence of large amounts of water (10–20 % HFIP v/v), which is unusual for weaker nucleophiles. Surprisingly, the reactions performed in the two-phase systems outperformed those in pure (100%) HFIP. The presence of the aqueous phase offers advantages over single-phase reaction media in terms of driving the reaction and product recovery. This system offers a new, largely aqueous medium for organic synthesis.