Revisiting Hydroxyalkylation of Phenols with Cyclic Carbonates

Abstract

Described is a tetrabutylammonium fluoride-mediated hydroxyalkylation reaction of phenols with cyclic carbonates. This operationally simple method enables the synthesis of a variety of aryl beta-hydroxyethyl ethers in good to excellent yields with a very small amount of catalyst loading (0.1-1 mol%). Of particular note is the efficient conversion of aromatic diols and phloroglucinol to the corresponding bis- and tris-hydroxyethylated products. To further showcase the versatility of this protocol, guaifenesin was prepared with a single step by the condensation of guaiacol and glycerol carbonate. We also developed a flow ethoxylation process permitting the continuous synthesis of multiflorol.