Synthesis of the ACDE tetracyclic skeleton in ceforalide B

Ceforalide B is a representative molecule with a complex rigid skeleton composed of ABCDE pentacycle in the benzenoid cephalotane-type norditerpenoids family, which contains five contiguous stereogenic centers involving an all-carbon quaternary center. An advanced intermediate with the ACDE rings has been synthesized from 3,5-dimethylphenol. While the organocatalyzed diastereoselective intramolecular Michael addition and aldol condensation reaction successfully secure the rapid construction of the ACD tricyclic framework, the Yb (OTf)3-catalyzed stereoselective hydroxymethylation, 1,2-addition, followed by a PDC-mediated oxidative rearrangement reaction also play important roles in elaborating this tricyclic core. Additionally, the late-stage C1 epimerization and the construction of bridging lactone for E ring by a Mitsunobu reaction were further used to build the tetracyclic carbon skeleton.