Total Synthesis of Neodolastane Diterpenes Trichoaurantianolides C and D

The
first total synthesis of trichoaurantianolides C and D is described.
An enantiocontrolled pathway leads to rapid construction of the tricyclic
carbon skeleton and establishes the trans-dimethyl
geometry of the quaternary bridgehead carbons via a reductive cyclization.
Application of the π-allyl Stille cross-coupling leads to a
nonracemic allylic alcohol as a prerequisite for the introduction
of asymmetry in the cycloheptane system. Two strategies have been
examined for elaboration of the unsaturated tetrahydrofuranyl ring
from a common tricyclic intermediate. These efforts reveal a number
of unanticipated issues of reactivity and significant stereochemical
requirements for a novel acyloin rearrangement as well as the elimination
and cyclodehydration of chiral α-hydroxy ketones. Key reactions
leading to completion of the synthesis include the stereoselective
addition of isopropenyllithium TMEDA complex and a facile chemoselective
oxidation with selenium dioxide.