Application of the Anionic Oxy-Cope Rearrangement to Stereocontrolled Synthesis of the A/B Subunit of Cytoxic 8,9-Seco-ent-kaurenes

Abstract
Methodology is described for expedient synthesis of the A/B framework of 8,9-seco-ent-kaurenes and for introduction of the 5-methylene-2-cyclopentenone moiety. In the first part of the study, a sequence of only six steps is necessary to convert 2-(hydroxymethylene) cyclohexanone to a key functionalized intermediate. Five of the transformations are 100% stereocontrolled as a direct result of complementary steric biases that operate in the desired direction. The final target is arrived at by selective protection/oxidation of the oxygenated centers. This first synthetic entry to the structural core of the titled diterpenes is expected to guide the future de novo acquisition of these cytotoxic agents.

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