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UBC Theses and Dissertations

New synthetic methods using β-keto esters and some useful applications in natural products syntheses Sum, Fuk-Wah


Results from studies on the cyclization of β-keto ester derivatives are presented. Electrophile- and acid-initiated cyclization of unsaturated β-keto esters, and the cyclization of epoxy β-keto esters provide interesting routes to some carbocyclic and heterocyclic compounds. Factors determining the predominance of C- or O-cyclization are discussed. The effect of olefin and epoxide substitution patterns on the reactivity and mode of cyclization was briefly investigated. A novel stereospecific synthesis of substituted alkenes from β-keto esters was achieved, along with the extension of this method to β-diketones (equation I) . Stereoselective synthesis of the E- and Z-enol phosphates of β-dicarbonyl compounds was developed. These enol phosphates reacted stereospecifically with lithium dialkylcuprates to give α, β-unsaturated carbonyl compounds. An efficient one-pot preparation of β, β-disubstituted- α, β-unsaturated esters from methyl acetoacetate based on these findings and the dianion chemistry of β-keto esters is also illustrated. The effect of a β-phosphoryloxy substituent on the reduction potential of an α, β-ethylenic carbonyl compound was estimated to be + 0.1 V. A plausible mechanism for the reaction between 1,3-dicarbonyl enol phosphates and lithium dialkylcuprates was proposed. A convenient route to the cyclohexene derivative 248 is described. This compound represents a useful synthetic substrate for the synthesis of several classes of natural products. The facile introduction of an isoprene unit, using methyl acetoacetate, in a stereoselective manner as indicated by equation ii is also demonstrated. The syntheses of three natural products, viz., Latia luciferin (328), (E, E)-10-hydroxy-3,7-dimethyldeca-2,6-dienoic acid (335) and mokupalide (347) are presented, which illustrate some useful applications of the new synthetic methods developed. While the syntheses of 328 and 335 show improvements over the previous preparations of these compounds, the synthesis of mokupalide (347) represents the first synthetic approach to this compound. [See thesis for Chemical Diagram]

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