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 pi-allyl Stile cross-coupling leads to a nonracermic 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 cycloclehydration of chiral alpha-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.