Unexpected diastereoselective acetylation of 1,8-dimethoxyanthracene adducts with maleic anhydride and dimethyl maleate

Friedel-Crafts acetylation of adducts between 1,8-dimethoxyanthracene and maleic anhydride or dimethyl maleate proceeds with a strong preference toward the syn diastereomer. This stereoselectivity is especially prominent for the anhydride counterpart. Dependence of the observed selectivity on the adduct structure is rationalized by the analysis of computed HOMO energies of the reactants and relative energies of the intermediate σ-complexes. The possible undesired intermolecular condensation of the anhydride did not take place because of steric hindrance. Structures of the reaction products were unambiguously confirmed by single-crystal X-ray diffraction (XRD). The reported stereoselectivity of acetylation provides facile access to compounds with the functionalized benzene ring in a syn arrangement with respect to the pendant carboxyl substituents. Acetylation of the adduct of maleic anhydride with 1,8-dimethoxyanthracene selectively produces the syn diastereomer without intermolecular condensation. This reaction provides convenient access to syn bicyclic phenols.