Rapid and Mild Metal-Free Reduction of Epoxides to Primary Alcohols Mediated by HFIP

Abstract

The reduction of epoxides is a powerful tool to access anti-Markovnikov alcohols, but reported methods are poorly compatible with strongly electronically deactivated substrates. Here, we describe a general method for the linear-selective reduction of styryl oxides incorporating strong electron-withdrawing groups. The method remains compatible with more traditional epoxide motifs, such as aliphatic and electron-rich styrene oxides. Other (hetero)cycles such as oxetanes, tetrahydrofurans, aziridines, and cyclopropanes can also be reductively opened. This user-friendly reaction relies on the combination of a Brønsted acid catalyst and hexafluoroisopropanol as a solvent, and thus, in contrast to existing epoxide reduction methods, it does not require anhydrous reagents or an inert atmosphere. The generated primary alcohols can be conveniently functionalized in situ by a dehydrative Friedel–Crafts arylation without preactivation.