Investigation of the Scope and Mechanism of the Palladium-Catalyzed Synthesis of Enantioenriched Allylic Esters from Prochiral (Z)-Allylic Alcohols and Progress Toward the Total Synthesis of (--)-Massadine

In Chapter 1, a review of the development and applications of enantioselective palladium(II) catalysts for the reactions of allylic imidates is provided. Planar chiral catalysts containing a metallocene unit were found to be the optimal catalysts for palladium(II)-catalyzed reactions. Cobalt oxazoline palladacycles (COP) are the most effective catalysts known for the enantioselective rearrangement of allylic imidates as well as a number of allylic displacement reactions.;In Chapter 2, the scope and mechanism of the COP-catalyzed reaction of prochiral (Z)-allylic trichloroacetimidates to form enantioenriched 3-carboxy-1-alkenes is investigated. The scope of this reaction was determined to be broad, tolerating a wide variety of organic functionality. Experimental and computational mechanistic analysis established that anti oxypalladation is the rate- and enantiodetermining step. DFT computational studies further established a model for enantioselectivity.;In Chapter 3, a review of recent synthetic approaches to the oxidized dimeric pyrrole imidazole alkaloids is provided. The first total syntheses of massadine, axinellamines, and palau'amine are described. Reports of progress toward the total synthesis of these natural products are also summarized.;In Chapter 4, progress toward the total synthesis of (-)-massadine is reported. The synthetic route features two key steps. The first is an Ireland-Claisen rearrangement of a trianionic allylic acetate that occurs with high stereospecificity. The second is an unprecedented intramolecular nitrone dipolar cycloaddition which stereoselectively constructs a fully substituted cyclopentane. Elaboration of cyclopentane intermediates to incorporate the bisguanidine functionality is described.