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UBC Theses and Dissertations

An approach to the synthesis of neoclovene Mar, Andrew


This thesis describes the investigation of two synthetic approaches to the keto tosylate 90, a key intermediate in a proposed synthesis of neoclovene. The first approach involved an efficient 9-step synthesis of the epoxy acetals 152 and 153 from indan-l-one 142. Dialkylation of 142 with methyl iodide followed by the reaction of the dimethyl ketone 143 with diethyl cyanomethylphosphorane gave the nitriles 144 and 145. Successive subjection of the nitriles to hydrolysis, hydrogenation, and reduction resulted in the formation of the aromatic alcohol 141. Treatment of the latter with lithium in liquid ammonia followed by regioselective hydrogenation of the disubstituted double bond of 149 with the homogeneous catalyst tris(triphenyl-phosphine)chlororhodium gave the olefin alcohol 150. Epoxidation of the double bond o£ the olefin acetal 151, corresponding to .the alcohol 150, with m-chloroperbenzoic acid gave a mixture of epoxy acetals 152 and 153 in quantitative yield. However, all attempts to obtain the keto tosylate 90 from the epoxy acetals failed to give synthetically useful yields of the desired products. This precluded further use of this approach. The second approach involved the synthesis of the olefin alcohol 179, a proposed intermediate in the synthesis of the keto tosylate 90. Thus, alkylation of isobutyronitrile 165 with allyl bromide followed by ozonolysis of the alkylation product gave the aldehydic nitrile 167. Successive treatment with cyclopentylidenetriphenylphosphorane, polyphosphoric acid, and alcoholic sodium hydroxide afforded the ketone 170. The ketone 170 was converted into the epoxy ketone 171 and the latter was reacted with methylenetriphenylphosphorane to yield the epoxy olefin 173. The latter was subjected to hydroboration-oxidation to produce the epoxy alcohols 174 and 175. The alcoholic functionality was protected as the acetate and the epoxide was reduced with tungsten hexachloride-n-butyllithium to give the olefin acetate 178 in 90% yield. Reduction of the olefin acetate with lithium aluminum hydride yielded the olefin alcohol 179. Unfortunately, due to the lack of time and material, this project was concluded at this point. A possible synthetic route to the keto tosylate 90 from the olefin alcohol 179 is given.

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