Selective tetrahydropyranylation under non-acidic conditions

We report that the tetrahydropyranylation of hydroxyl groups, exhibiting especially very low nucleophilicities, can be achieved by means of Mitsunobu reaction with 2-hydroxytetra-hydropyran. This reaction led to the protection of phenols and pyridinols without the use of an acidic catalyst. For instance hydroxypyridines could not be protected by dihydropyran under acidic conditions, whereas they underwent a smooth tetrahydropyranylation under Mitsunobu conditions. The method is selective for a phenol over an alcohol.