Anionic Polycyclization Entry to Tricycles Related to Quassinoids and Terpenoids: A Stereocontrolled Total Synthesis of (+)-Cassaine

A full
account of our anionic polycyclization approach to access
highly functionalized tricycles related to quassinoids and terpenoids
from several optically active bicyclic enone systems and Nazarov reagents
is presented. (+)-Carvone is the only chiral source used to fix the
entire stereochemistry of all of the tricycles, and the stereochemical
outcome of this process was unambiguously determined by X-ray crystallographic
analysis. The utility of this strategy was demonstrated by the stereocontrolled
construction of advanced tricycles related to the highly potent anticancer
natural product bruceantin, a member of quassinoid family, and the
total synthesis of the cardioactive terpenoid (+)-cassaine, a nonsteroidal
inhibitor of Na+-K+-ATPase.