Catalytic asymmetric synthesis of allylic aryl ethers, and, Progress toward the total synthesis of palau'amine, axinellamines A-D, and massadine

In chapter 1, a mild catalytic-asymmetric etherification that uses the palladium(II) catalyst [COP-OAc]2 and phenol nucleophiles to construct 3-aryloxy-1-alkenes in high enantiopurity and high yield is described. Attractive features of the method include the following: only 1 mol % of the commercially available catalysts (S)- or (R)-[COP-OAc] 2 is used; products are produced in high yields and enantiopurity; the branched product is produced with unprecedented regioselectivity; and the method is compatible with the presence of base-labile functionality in either reactant.;In chapter 2, the isolation, characterization, and biological activity of the pyrrole-imidazole alkaloids palau'amine, axinellamines A--D and massadine are reviewed. The proposed biosynthesis of these alkaloids is described and several synthetic approaches toward these alkaloids are discussed.;In chapter 3, the synthesis of a simplified analog of palau'amine containing the complete hexacyclic ring system is described that utilizes an intramolecular dipolar cycloaddition of an azomethine imine and a dihydroproline ester. Comparison of NOE data obtained for the hexacylic analog to that of palau'amine supports the recent structural revision in which the azabicyclo[3.3.0]octane ring system is trans- and not cis-fused as originally reported. A concise and high yielding route to access the tetracyclic core of massadine is also described that features an intramolecular nitrone dipolar cycloaddition. In addition, a model system to study nitrone dipolar cycloadditions of oximes containing a-oxidation is described; single X-ray crystal analysis confirmed the relative configuration of the [3.3.0]cyclopentaisoxazoline cycloadduct.