Stereocontrolled Additions to a Rigid Bicyclo [3.3.0] Octane Ring System
Abstract
Organisms in nature often produce complicated molecules difficult to synthesize in the laboratory. Dolabellanes have demonstrated significant anti-tumor capability but are found principally in marine species inhabiting sensitive ecosystems. Interest in their synthesis is high. These compounds contain a multi-functionalized eleven-membered ring fused to a cyclopentane ring bearing three stereocenters. This project investigated means of introducing stereocenters relevant to dolabellanes to simplify their ultimate synthesis. The project has postulated employing a fused bicyclopentane system can permit the creation of stereocenters with predictable chirality. This is made possible by the rigidity of the fused system, which is energetically constricted to one conformation. Ketone in a previously prepared molecule was converted into an alkene conjugated with a carbonyl-containing ethyl ester. Two reaction methods were studied. The Horner-Wadsworth-Emmons reaction was employed using triethyl phosphonoacetate as the reagent; the Wittig reaction was then explored to introduce the same carbon-carbon double bond motif using an ylide reagent. The latter reaction proved to be more successful and was used in subsequent reactions. Creation of a quaternary stereocenter was first explored. Continuing, tertiary stereocenters were investigated via two reactions. Catalytic hydrogenation consisted of the reaction of hydrogen gas with ester mediated by the surface properties of several metallic catalysts. The second reaction employed Grignard reagents to add directly to the ketone carbonyl of the fused bicyclopentane. Sterics of the convex side of the molecule caused the Grignard reagents to act as bases, extracting the hydrogen bonded between the carbonyls. Secondary stereocenters were created through the use of hindered reduction reagents attacking the ketone carbonyl of the fused bicyclopentane. Spectroscopic methods allowed conclusive confirmation of structure and reaction products.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 05, 2008
- Accession Number
- ADA486710
Entities
People
- John B. Moore