Synthesis of dl-Shikonin by Vanadium(II)-Assisted Cross-Coupling and Electrooxidation of Aromatic Nucleus

Torii, S.; Akiyama; K.; Yamashita, H.; Inokuchi, T. Bull. Chem. Soc. Jpn. 1995, 68, 2917.

Vanadium(II)-assisted cross-coupling of 2-formyl-1,4,5,8-tetramethoxynaphthalene and 3-methyl-2-butenal was employed for introduction of the side chain of dl-shikonin. 2-(1-Hydroxy-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxynaphthalene was prepared by the pinacol coupling and the subsequent palladium-catalyzed hydrogenolysis of the carbon-oxygen bond at the allylic position of the diol carbonate. Electrochemical oxidation of the 2-substituted 1,4,5,8-tetramethoxynaphthalene followed by reductive acetylation with zinc and the subsequent electrooxidation of the resulting 5,8-diacetoxy-1,4-dimethoxynaphthalene, afforded the corresponding 1,4-naphthoquinone diacetate, whose alkaline hydrolysis furnished dl-shikonin.