Total\nSynthesis of the Norcembranoid Scabrolide B\nand Its Transformation into Sinuscalide C, Ineleganolide, and Horiolide

It was recognized\nonly recently that the sister norcembranoids\nscabrolides A and B have notably different carbotricyclic scaffolds.\nTherefore, our synthesis route leading to scabrolide A could not be\nextended to its sibling. Rather, a conceptually new approach had to\nbe devised that relied on a challenging intramolecular alkenylation\nof a ketone to forge the congested central cycloheptene ring at the\nbridgehead enone site; the required cyclization precursor was attained\nby a lanthanide-catalyzed Mukaiyama–Michael addition. The dissonant\n1,4-oxygenation pattern was then installed by allylic rearrangement/oxidation\nof the enone, followed by suprafacial 1,3-transposition. Synthetic\nscabrolide B was transformed into sinuscalide C by dehydration and\ninto ineleganolide by base-mediated isomerization/oxa-Michael addition,\nwhich has potential biosynthetic implications; under basic conditions,\nthe latter compound converts into horiolide by an intricate biomimetic\ncascade.