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UBC Theses and Dissertations

Approaches to the synthesis of cadinene sesquiterpenes and the birch reduction of some 4-alkyl-[delta]1,9-2-octalones Phillips, Wynona M.


Part of this thesis describes the investigation of several synthetic approaches to the cadinane group of sesquiterpenes. The first approach investigated the preparation of a possible key intermediate of type 118 using the known octalone 114 as starting material. However all attempts to obtain octalone 116, a necessary intermediate in this sequence were unsuccessful. This precluded further use of this approach. The second approach involved preparation of several cross-conjugated dienone systems (125, 133, 139 and 141) and the study of 1,4-conjugate addition of an alkyl group by means of cuprous ion catalyzed Grignard reagents and lithium dialkylcuprate reagents. Use of reagents in which the alkyl group was methyl or primary effected the desired 1,4-conjugate addition. However when isopropylmagnesium bromide or lithium diisopropylcuprate reagents were tried no addition products were detected. Evidence is presented which indicates that enolization of the keto system was the main reaction pathway in these cases. The final and most successful approach described is the condensation-annelation approach where condensation between a vinyl ketone such as 144 and a substituted cyclohexanone derivative of type 143 was investigated. Octalones 162 were prepared by the enamine-annelation reaction employing vinyl ketone 144 and the enamine of keto alcohol 158. The stereochemistry of octalones 162 was then established. The mixture of epimeric octalones 162 was degraded to decalones 165a and 165b. The stereochemistry of these decalones was unambiguously shown by a combination of chemical and spectroscopic methods. Octalones (162a + 162c) were converted into thioketal 166 by treatment with ethanedithiol and boron trifluoride etherate. Thioketal 166 was converted into alcohol 167 by desulphurization employing Raney nickel. Treatment of alcohol 167 with chromium trioxide in pyridine afforded octalone 168. Octalone 168 was converted into (+)-cadinene dihydrochloride by treatment of the former with methyllithium followed by treatment of the resultant 3° alcohol with anhydrous hydrogen chloride in ether. The Birch reduction of octalones of type 170 is described. The octalones were prepared by 1,4-conjugate addition of lithium dialkyl- cuprate reagents to the cross-conjugated dienones of type 171. The preparation of the corresponding authentic cis- and trans-fused decalones is described. The results of Birch reduction of octalones 188 to 192 revealed a higher percentage of cis-fused decalone product than normally obtained in other substituted Δ¹•⁹-2-octalone systems. The results also indicated that as the bulk of the C₄ substituent was increased the product ratio of cis-fused decalone to trans-fused decalone also increased. The substituent at the C₁₀ position also effected the ratio of cis:trans decalone obtained. Possible explanations for these results are presented.

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