Preparation of Substituted Enol Derivatives from Terminal Alkynes and Progress Toward the Total Synthesis of Nigricanoside A
DeBergh, John Robbins
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This manuscript consists of two chapters. The first chapter describes the preparation of stereodefined enol derivates of alpha-branched aldehydes from terminal alkynes. Specifically, alkenyl alanes, derived from the methylalumination of alkynes, are shown to be efficiently oxygenated with peroxyzinc species. The resulting metallo-enolate may be trapped with benzoic anhydride, acetic anhydride, and TESOTf to generate E-trisubstituted enol esters and silanes. Traditional approaches to these types of olefins involve enolization of aldehydes; these methods are often inefficient and generally afford mixtures of olefin stereoisomers. Therefore, the methodology presented Chapter One represents a conceptually novel and useful strategy. The development and scope of the methylalumination-oxygenation reaction is discussed along with applications of the enol derivatives in the context of asymmetric and natural product synthesis. Finally, the alkenyl alane intermediates are shown to be efficiently aminated to afford ene-hydrazine products. The second chapter involves the progress towards the asymmetric synthesis and structural assignment of nigricanoside A, a potent antimitotic glycolipid isolated from marine green algae. A convergent synthetic route is presented along with an analysis the natural product’s relative and absolute stereochemistry. Various diastereomers of orthogonally protected subunits of nigricanoside A were prepared through vinyl-metal additions to alpha-hydroxy aldehydes. The chapter includes attempts to join the subunits through etherification reactions as well as descriptions of future strategies to effect etherification.