Synthetic routes from camphor to longicamphane and picrotoxane derivatives

Paul Joseph Cachia
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
more » ... e 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.
doi:10.14288/1.0060805 fatcat:fui64uwfs5h5lpmrwndrywznri