Regiospecific synthesis of quinizarin and naphthazarin derivatives by cycloaddition

The diene (E)-1,1,4-trimethoxybuta-1,3-diene underwent regiospecific cycloaddition to derivatives of 2(3)-chloro-1,4-naphthoquinone. The resulting adducts were aromatized to give 1,4-dioxygenated anthraquinones. The latter were obtained as derivatives of quinizarin dimethyl ether or of quinizarin monomethyl ether depending on the conditions of aromatization. Cycloaddition of the diene to non-halogenated naphthoquinones proceeded similarly, orientation being controlled by substituents in the benzenoid ring. Analogous reaction of the diene with benzoquinones gave 5,8-dioxygenated naphthoquinones (naphthazarins), generally in limited yield. The procedure has been applied to synthesis of the mould metabolites helminthosporin and cynodontin.