Enantiospecific synthesis of (+)-(1S,2R,6S)-1,2- dimethylbicyclo[4.3.0]nonan-8-one and (-)-7-epibakkenolide-A

Article abstract of DOI:10.1016/S0040-4020(98)00672-3

Synthesis of the chiral bicyclic ketone mentioned in the title starting from R-carvone, and its elaboration to 7-epibakkenolide-A is described. Conjugate addition of dimethyl copperlithium to R-carvone followed by alkylation of the intermediate enolate generated the allylated compound 6, which was transformed into the diketone 12 via a sequence of reactions comprising regiospecific Wacker oxidation, ozonation-Criegee rearrangement as key reactions. Intramolecular aldol condensation followed by catalytic hydrogenation converted the diketone 12 into the bicyclic ketone (+)-3, the optical antipode of the compound derived from the sesquiterpenes bakkenolide- A and fukinone. A 5-exo-dig radical cyclisation based strategy transformed the bicyclic ketone 3 into chiral 7-epibakkenolide-A.