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UBC Theses and Dissertations

Conformationally controlled reactions in 14-membered macrolides Keller, Thomas Hugo


The conformationally controlled reactions of macrolides 42, 43, 72 and 74 were investigated. Treatment of these 14-membered lactones with hydride reducing agents and organocopper reagents led to diastereoselective product formation. The product distributions could be rationalized using low energy starting material or product conformations. A detailed conformational analysis involving MM2/MMP2 calculations and X-ray crystallographic studies led to a simple model for determining these low energy conformations. In order to simplify the identification of ring conformations, an improved procedure for the generation of polar maps was developed. With the aid of polar maps, a previously unknown low energy conformation for 14-membered rings was discovered. The discovery of this new conformation led to an improved nomenclature system for large rings, which considers the number of bonds separating both corner and pseudo corner atoms. Under this proposed nomenclature, the newly discovered conformation is designated the [34'3'4'] conformation. The work described in this thesis also led to a useful method for assigning the stereochemistry of trimethylsilyl enol ethers. Nuclear Overhauser effect difference spectroscopy (NOEDS) was used to unambiguously distinguish between E and Z trimethylsilyl enol ethers. One advantage of this technique over the widely used ¹³C NMR method is that only one isomer is required to accurately assign the E or Z geometry. [Formula Omitted]

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