Preparation of 5-Bromotetronates and a New Concept for the Synthesis of Aflatoxins and Related Structure Types. Tributyltin hydride versus Palladium-Promoted Intramolecular Hydroarylation

Article abstract of DOI:10.1016/S0040-4020(01)85124-3

The coupling of suitably functionalized o-iodophenols (e.g. 6) with 4-alkoxy-5-bromo-2(5H)-furanones (5-bromotetronates) (10a-e) gave precyclic aflatoxin M₁ A-C building blocks (7, 14, 17c).Two cyclization modes for obtaining the ABC-moiety were investigated and compared.Whereas the Bu3SnH-induced reaction worked well for simple model compounds, it failed for the more functionalized compounds.The palladium-mediated procedure allowed the synthesis of potential aflatoxin M₁ precursors such as 18c.An improved procedure for obtaining O-alkylated tetronates (9a-g) is described.The tetronates were converted into 5-bromotetronates (10a-e, h) under controlled free radical conditions.For example, the narthogenin precursor 10a was prepared to the exclusion of undesired isomer 11, in 62 percent yield.Finally, other benzoannulated heterodiquinanes, e.g. a desoxyeserolin precursor 24, were obtained by both cyclization procedures in good toexcellent yield.