Total Synthesis of Linear Polyprenoids. 3. Syntheses of Ubiquinones via Palladium-Catalyzed Oligomerization of Monoterpene Monomers

Article abstract of DOI:10.1021/ja00221a040

A general methodology for highly regio- and stereoselective Pd(0)-catalyzed, stepwise allylic coupling of bifunctional monomers was developed, representing a practical approach for total synthesis of naturally occuring polyprenoids.As an example, the total synthesis of the cardiovascular agent ubiquinone 10 (coenzyme Q10), as well as shorter ubiquinones, was carried out via selective coupling of monomers easily derived from geraniol that contain either one or two reacting functional end groups.One of these funcionalities is a latent allylic electrophyle activated by the Pd(0) catalyst and the other is a latent nucleophile activated by an appropriate base.After the desired decaprenyl carbon skeleton of Q10 was achieved, the synthesis was completed by removal of the activating groups: Methyl ester was deleted via a highly efficient demethoxycarbonylation procedure involving 4-aminothiophenol and catalytic amounts of cesium carbonate, and the allylic sulfones were deleted by Pd(0)-catalyzed allylic reduction.Finally, oxidation of the aromatic ring to quinone affords ubiquinone 10.