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UBC Theses and Dissertations

Conformationally controlled reactions of unsaturated macrocyclic lactones and keto lactones Fenster, Erik


As part of a study of the chemistry of macrocyclic compounds in our laboratory, the 14-membered unsaturated lactones 29 and 30 were synthesized with high stereoselectivity (>16:1 EIZ) via the ring closing olefin metathesis (RCM) reaction of the open chain diene esters. The configuration of the double bond in these unsaturated lactones was determined by 1H homonuclear decoupling NMR experiments. Equilibrium studies demonstrated that the RCM reaction proceeds under thermodynamic control in the cases of 29 and 30. The keto lactones 67 and 68 were synthesized via the hydroboration of 30 followed by TPAP oxidation of the hydroxy lactone products. The conformationally controlled reactions of the macrocyclic lactones 29, 30, 67 and 68 were investigated. Treatment of the unsaturated lactone 29 with borane tetrahydrofuran complex, disiamylborane and 9BBN led to the formation of the hydroxy lactones 47 and 48 in a 1:1 regioisomeric ratio. Treatment of the unsaturated lactone 30 with the same hydroborating reagents led to the formation of the hydroxy lactones 51, 52, 53 and 54 in a 1:1 regioisomeric ratio but with good 7r-face selectivity (>7:1 using 9BBN). The epoxidation of 30 using MCPBA and methyl(trifluoromethyl)dioxirane, leading to epoxides 63 and 64 also showed moderate 7t-face selectivity (>3:1 using MCPBA at -78 °C). Treatment of keto lactones 67 and 68 with NaBH4 and K-Selectride under a variety of reaction conditions led to the formation of hydroxy lactones 52, 53 and 51, 54, respectively. The hydroxy lactones were obtained in good stereoselectivity (>10:1 using K-Selectride at -78 °C) in the case of 67, and in low stereoselectivity (1:1.5 using K-Selectride at -78 °C) in the case of 68. In general, the stereoselectivity exhibited in the reactions of these macrocyclic lactones could be rationalized from the conformational analysis of the starting materials or the products. The relative stereochemistry of the stereogenic centers within the compounds synthesized during the course of the project were successfully assigned with the use of chemical correlations and Xray analysis.

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