Rhodium-catalyzed epoxide-opening cascades toward brevisin and hemibrevetoxin B

Abstract

CHAPTER I. Rhodium-Catalyzed Epoxide-Opening Cascades: Formal Synthesis of (-)-Brevisin [chemical formula inserted] [Rh(CO)₂Cl]₂ was found to be an effective catalyst for endo-selective cyclizations and cascades of epoxy-(E)-enoate alcohols, thus enabling the synthesis of oxepanes and oxepanecontaining polyethers from di- and trisubstituted epoxides. Syntheses of the ABC and EF ring systems of (-)-brevisin via all endo-diepoxide-opening cascades using this method constitute a formal total synthesis and demonstrate the utility of this methodology in the context of the synthesis of marine ladder polyether natural products CHAPTER II. Synthetic Studies Toward Hemibrevetoxin B [chemical formula inserted] We report progress toward a biomimetic epoxide-opening cascade of the marine ladder polyether hemibrevetoxin B. Model studies demonstrate the ability of both [Rh(CO)₂Cl]₂ and cationic Rh(I) species to override the typical exo-directing of proximal methyl groups on in epoxy alcohol cyclizations for the synthesis of oxepanes. The synthesis of tri-epoxide cascade precursor and initial investigations toward an epoxide-opening cascade are described as well.