UBC Theses and Dissertations
Synthetic routes from camphor to longicamphane and picrotoxane derivatives Cachia, Paul Joseph
Camphor has been functionalized at the C-(8) position by treating (+)-3,3-dibromocamphor with bromine and chlorosulphonic acid. A mechanistic rationalization is proposed for this transformation which accounts for the presence of the minor side products that form during 8- and 9-bromination. (+)-8-Bromo-camphor produced by this method was subsequently used as a key intermediate in sesquiterpenoid synthesis. Approaches to the synthesis of both the longicamphane and picrotoxane carbon frameworks are discussed. Our approach to the synthesis of the longicamphane framework involved intramolecular Michael-addition of 9-oxocampherenone. While investigating a proposed synthesis of 9-oxocampherenone via Meyer-Schuster rearrangement of 8-(3-hydroxy-3-methyl-l-butynyl)camphor ethylene acetal an interesting new reaction occurred providing the polycyclic ring system (+)-6,7-dimethyl-6-(l-oxo-2-methylpropyl)tricycle [4 • 2 • 1 • 0³ ' ⁷] nonan-9-one whose structure was determined by X-ray erystallographic analysis. A mechanism for its formations is proposed. Attempts to synthesize 9-oxocampherenone by allylic oxidation of 9-hydroxycam-pherenone and its ethylene acetal derivative are also discussed. Our synthetic approach to the picrotoxane framework involves Baeyer-Villiger oxidation-translactonization of a suitable copacamphor-type derivative. In our first approach the attempted synthesis of 4-hydroxycopacamphor via intramolecular epoxide cyclization of 8-(1,2-epoxy-3-methylbutyl)camphor provided the tricyclic ketol 1,6-dimethyl-4-(l-hydroxy-2-methylpropyl)tri-cyclo [4 • 3 • 0 • 0³ ' ⁷] nonan-2-one . This 5-membered ring cyclization product was formed exclusively during the reaction. The strategy was revised to exclude 5-membered ring formation; the cyclization would be performed on 8-acetoxycampherenone epoxide. The synthesis of 8-acetoxycampherenol methyl ether is discussed and its potential conversion to 8-acetoxycampherenone epoxide is described.
Item Citations and Data