cis-Dihydrocatechols as precursors to highly oxygenated troponoids. Part 2. Regiocontrolled syntheses of stipitatic and puberulic acids

Stipitatic and puberulic acids, 1 and 2 respectively, have both been prepared in a fully regiocontrolled manner using commercially available cis-1,2-dihydrocatechol 3 as the common starting material. In the case of the former acid, compound 3 was converted over six simple steps into the ester 12. Oxidation of this latter compound produced the σ-homo-o-benzoquinone 13 which acted as a Michael acceptor when treated with methoxide ion and the resulting conjugate could be trapped with acetic anhydride to give the acetoxy enone 14. Base-promoted ring-expansion of 14 then afforded the troponoid 15, the acquisition of which constitutes a formal total synthesis of stipitatic acid. Attempts to develop an analogous synthesis of puberulic acid failed. However, a successful synthesis of this natural product was achieved by elaborating the tetra-oxygenated compound 25, which is readily prepared from the diol 3, to the bromotropolone 28. Palladium-catalysed methoxycarbonylation of this latter compound, followed by hydrolysis of the intermediate ester afforded the acid 29, the structure of which was established by X-ray methods. Two-fold demethylation of compound 29 then delivered puberulic acid 2.