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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/27609

Title: Synthesis and Reactions of Unsymmetrical Oxabicyclic Alkenes: Studies toward the Total Synthesis of Phorbol and Prostratin
Authors: Webster, Robert Alan
Advisor: Lautens, Mark
Department: Chemistry
Keywords: Synthetic Organic Chemistry
Catalysis
Issue Date: 13-Jun-2011
Abstract: Chapter 1 details our investigation into the Diels-Alder reaction between arynes and chiral furans and pyrroles for the synthesis of unsymmetrical [2.2.1] oxabicyclic and azabicyclic scaffolds as single enantiomers. It was discovered that the diastereoselectivity of the aryne Diels-Alder reaction was sensitive to conformational effects that could be exploited to obtain both high yields and dr. Stereoselective synthesis using arynes is an overlooked field, and this contribution represents one of only three such examples in the literature. The desymmetrization of meso [2.2.1] oxabicyclic systems by intramolecular cyclization/ring- opening was studied, and a cationic Rh/t-Bu-Josiphos catalyst was developed that delivered polyclic dihydronaphthalene products in excellent yield and ee. These catalyst conditions were used for the ring-opening of an enantiomerically pure unsymmetrical oxabicyclic alkene, which led to the discovery that ring-opening proceeded with complete reagent control. A regiodivergent resolution was designed that gave pairs of enantiomerically enriched dihydronaphthalenes from unsymmetrical racemic starting materials. In chapter 3, the scope of the regiodivergent resolution was expanded to include the ring-opening of remotely-substituted oxabicyclic alkenes and furan-hetaryne Diels-Alder adducts. The utility ii of the method was demonstrated by using it to synthesize two important API molecules from a single racemic precursor. Finally, chapter 4 describes our lab’s efforts toward the total synthesis of the natural products phorbol and prostratin that features the ring-opening of an unsymmetrical [3.2.1] oxabicycle as the key step. Advanced intermediates (requiring >30 linear steps) were synthesized on gram- scale. The entire carbon framework was successfully installed, and our efforts to complete the synthesis are discussed.
URI: http://hdl.handle.net/1807/27609
Appears in Collections:Doctoral

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