Reaction of phenyl vinyl sulfoxide with the lithium enolates of simple ketones of varying ring size (cyclopentanone, cycloheptanone and cyclooctanone) under controlled cyclisation conditions followed by subsequent oxidation resulted in the formation of the bicyclo[n.2.0]alkan-1-ols 253-255, 262, 263, 265, 268 and 269 in conjunction with alkylated species 256, 257, 264, 266 and 267. The ratio of bicyclo[n.2.0]alkan-1-ols to alkylated ketone formation observed was dependent on a number of factors including the variation of enolate reactivity between the different ring sizes, conversion of phenyl vinyl sulfoxide, time, temperature and concentration of reaction and the stability and steric strain observed in the final bicyclo[n.2.0]alkan-1-ol product. X-ray crystal structures of 253, 262 and 265 were obtained and a structural study showed that as the overall steric strain in the bicyclo[n.2.0]alkan-1-ol product is decreased there is a corresponding increase in product distribution in favour of bicyclo[n.2.0]alkan-1-ol formation in conjunction with increased yields. Selected substituted and functionalised ketones (2-methylcyclopentanone, 2,6-dimethylcyclohexanone, 2-methylcyclohexanone and 1,4-cyclohexanedione mono-ethylene ketal) also reacted in the cyclisation reaction to give bicyclo[n.2.0]alkan-1-ols 270, 271, 277, 278, 281, 282, 285 and 286 in conjunction with alkylated products 272, 279, 280, 283, 284 and 287. Incorporation of substitution at the bridgehead and C2 position had a role in the preference of the major stereochemical isomer observed for a bicyclo[n.2.0]alkan-1-ol (n = 3, 4). A structural comparison of the X-ray crystal structures of 278, 281 and 286 indicated that the pseudo chair conformation of the six-membered ring influenced ring torsion and bond angles in the bicyclo[4.2.0]octanol ring system. Two model studies were selected to illustrate the potential application of the cyclisation process as methodology towards natural product synthesis or complex ring systems. No bicyclo[n.2.0]alkan-1-ol formation was evident in an intramolecular example using the starting ketone 291 in which the electrophile is tethered to the ketone. 2,6-Dimethyl-2-cyclohexen-1-one 301 considered as a model study towards the synthesis of the antibiotic mellolide, upon reaction with phenyl vinyl sulfoxide and oxidation displayed poor reactivity. The novel bicyclo[2.2.2]octanones 303, 304 and 305 were formed in very low yields. The lack of reactivity of the ketones 2,6-dimethyl-2-cyclohexen-1-one, 1,2-cyclohexanedione and 1,4-cyclohexanedione towards bicyclo[n.2.0]alkan-1-ol formation suggested that conjugation in the enolate prior to reaction with phenyl vinyl sulfoxide was not favourable. The non-reactivity of these ketones and the hindered ketone camphor indicated the potential limitations to the cyclisation methodology. However, conversion of the ketal functionality of 286 to a ketone resulted in the formation of the functionalised bicyclo[4.2.0]octanol 288 providing positive indications for further synthetic applications.
| Identifer | oai:union.ndltd.org:ADTP/195286 |
| Date | January 2004 |
| Creators | McCleary, Michelle Angela, n/a |
| Publisher | Griffith University. School of Science |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | http://www.gu.edu.au/disclaimer.html), Copyright Michelle Angela McCleary |
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