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Chemistry of the anions from isoxazolin-5-ones ; Lactone synthesis via β-keto ester dianion alkylaton

University of British Columbia

In part I of this thesis an examination of the utility of isoxazolin-5-ones, e.g. 114, as B-keto ester dianion equivalents is presented. Generation of the anion of isoxazolin-5-one 114 and reaction with various electrophiles gave products 140 in fair to good yields. In particular, the cases where [See thesis for diagram] E=TMS, Br, C₆H₅S, and C₆H₅Se illustrate that the chemistry of the anion of isoxazolin-5-ones is complimentary to that of β-keto ester dianions. Several routes or potential routes to the preparation of unsaturated isoxazolin-5-ones are also discussed. One of these pathways involves the condensation of Wittig reagent 141 with aldehydes. The success of this plan was [See thesis for diagram] demonstrated by the preparation of unsaturated isoxazolin-5-ones 142, R= C₆H₅- and CH₃(CH₂)₄₋, R'=H. Finally, several strategies for the cleavage of isoxazolin-5-ones to β-keto esters were investigated. In part II of this dissertation, the synthesis of large ring lactones via an internal β-keto ester dianion alkylation is described (equation i). The β-keto ester halides 262 were [See thesis for diagram] prepared by the alcoholysis of acetyl Meldrum's acid 253 with 1,n-bromoalcohols. The study of the cyclization of β-keto ester [See thesis for diagram] halide 262g revealed that elimination as well as intramolecular alkylation often occurred (equation ii). The effect of [See thesis for diagram] temperature, leaving group, solvent, and counterion on the cyclization process was therefore examined. The results of this investigation have shown that cyclization was optimized when the halide 262 was added to three equivalents of lithium diisopropylamide in tetrahydrofuran (0° ￫ RT) . These conditions provided β-keto lactones when the chain length n ≥ 9, while elimination predominated when n ≤ 8. Finally, the preparation and intramolecular alcoholysis of the hydroxyacyl Meldrum's acid 295 was conducted and gave the fourteen-membered β-keto lactone 266e in fair yield. [See thesis for diagram]

Text

2010-03-29

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http://hdl.handle.net/2429/22861

Chemistry

University of British Columbia

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