Hosea Nelson

3:15 p.m. – Public research seminar, Taylor Auditorium
4:30 p.m. – Research proposal, A81

From Target-Directed Synthesis to Reactivity-Driven Methodology: Strategies to Prepare Complex Molecules

I.  A general synthetic strategy for the transtaganolide and basiliolide natural products will be presented.  Our approach features an Ireland–Claisen/Diels–Alder cascade reaction that rapidly provides the stereochemically complex core common to all members of the natural product family. The unprecedented oxepinone C-Ring is constructed via palladium-catalyzed annulation of a methoxyacetylide derivative. Finally, enantioselectivity is achieved via a highly asymmetric (–)-sparteine-mediated silylation reaction. The biosynthetic implications of our synthetic efforts will be discussed.

II.  The utilization of aryldiazonium cations in chiral anion phase-transfer (CAPT) reactions enables the development of several enantioselective methodologies.  Addition reactions of enolate and indole nucleophiles with aryldiazonium/chiral phosphate ion pairs results in enantioselective C–N bond formation. Furthermore, these ion pairs are utilized in Palladium-Heck chemistries to achieve highly enantioselective arylation. The utility of these methods is demonstrated through the preparation of enantioenriched complex molecules including macrocycles, pyrroloindolines, and conformationally –constrained tyrosine analogues.