Chelation controlled regiospecific O-substitution of myo-inositol orthoesters: convenient access to orthogonally protected myo-inositol derivatives

A general method for the completely regioselective protection of the three secondary hydroxyl groups of orthoester derivatives of myo-inositol, utilizing the subtle differences in reactivity exhibited by its alkali metal alkoxides due to differences in their ability to form chelates, is described. This method provides convenient access to orthogonally protected myo-inositol derivatives. A comparison of the methylation of racemic 4-O-trityl-myo-inositol 1,3,5-orthoformate in the presence of sodium or lithium ions showed that stabilization of the C4-alkoxide by chelation with lithium overrides steric hindrance offered by the C6-axial substituent in deciding the regioselectivity during the nucleophilic O-substitution.