Direct and enantiospecific ortho-benzylation of phenols by the Mitsunobu reaction

Abstract

ortho-Substituted phenol derivatives with high optical purity have been obtained directly by Mitsunobu reaction between an appropriate phenol and an optically active benzyl alcohol. In this reaction, the chemical yield was well balanced with the optical purity of the ortho-substituted compound when 5 equiv. of phenol was allowed to react with 1 equiv. of alcohol in a solvent such as dichloroethane or toluene. In addition, it was confirmed by an X-ray analysis of the product that stereochemical inversion of the asymmetric centre took place in this reaction, as well as the usual Mitsunobu reaction. This reaction is useful in the preparation of optically active phenol derivatives possessing a diarylmethane moiety.