APPLICATIONS OF Rh(I)-CATALYSIS TO NATURAL PRODUCT SYNTHESIS: ROUTES TO OVALICIN AND GUANACASTEPENE A
Transition metal-catalyzed carbon-carbon bond formation is an efficient method to rapidly increase molecular complexity via skeletal reorganization and/or cycloaddition processes. The mild conditions, functional group compatibility, and high regio- and stereoselectivities of these transition metal-catalyzed reactions are just a few reasons for their prominence in natural product synthesis.
The first section describes a route to ovalicin via an allenic Alder-ene reaction using Rh(I)-catalysis. The scope of the novel allenic Alder-ene reaction using Rh(I) and Ir(I) catalysts has been extended to differentially substituted 1,1,3-trisubstituted allenes. The allenyl substitution pattern can give three possible cross-conjugated triene products. The selectivity of this transformation can be controlled by varying reaction temperature, solvent, catalyst and functional groups. Progress towards the synthesis of ovalicin using this triene forming protocol is described.
The second section describes a route to guanacastepene A via a Rh(I)-catalyzed allenic cyclocarbonylation reaction. Efficient synthetic reactions, readily available and inexpensive starting materials and practical and convenient conditions all contribute to the success of a synthesis of the carbocyclic core of guanacastepene A and are the primary focus of the first half on this chapter. Upon the highly efficient formation of the carbocyclic core to guanacastepene A, our attention turned to the installation of an angular methyl group at C13. The routes evaluated to effect this transformation were a 1,4-conjugate addition, a reductive ring opening of a cyclopropyl ketone, and a radical cyclization of a bromo-silane moiety.
Advisor:Dennis P. Curran; Paul E. Floreancig; John S. Lazo; Kay M. Brummond
School:University of Pittsburgh
School Location:USA - Pennsylvania
Source Type:Master's Thesis
Date of Publication:06/22/2007