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Enzymatic routes to generic building blocks leading to chiral tertiary alcohols
[Thesis]. Manchester, UK: The University of Manchester; 2012.
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Abstract
AbstractTertiary alcohols are a common functional group in many natural products, pharmaceuticals and agrochemicals. The ability to produce highly enantiomerically pure tertiary alcohols is therefore an important goal in synthetic chemistry.The synthesis of chiral tertiary alcohol precursors has been achieved via enzymatic desymmetrisation with the lipase Amano L, AK to generate (S)-(2-(hydroxymethyl)oxiran-2-yl)methyl acetate in 42% isolated yield and 97% enantiomeric excess. The reaction was also attempted with an immobilised lipase from R. miehei yielding the product in 82-90% yield and up to 89% ee. The enantioselective ring-opening of the epoxide using different amines has been developed in high yields generating enantiomerically pure β-amino tertiary alcohol products. However, an undesired intramolecular migration of the acetyl group was observed during the epoxide opening with aliphatic primary amines resulting in prochiral triol products. To avoid such an intramolecular migration a TBS-protected derivative has been used to prepare the tertiary alcohol products with primary amines in good yields (43%-83%), without any loss of enantiomeric excess of the formed ‘pseudo’-enantiomer .(S)-(2-(hydroxymethyl)oxiran-2-yl)methyl acetate has the potential to generate a large diversity of compounds; this reagent was also used as the starting material to generate azetidines in high yields.