Document Type

Theses, Masters

Master Thesis

Master thesis

Rights

Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence

Disciplines

Pharmacology and pharmacy

Publication Details

Successfully submitted for the award of Master of Philosophy (M.Phil) to the Technological University Dublin, 2010.

Abstract

In this work, a route for the conversion of arene cis-dihydrodiols to their trans isomers was examined. Arene trans-dihydrodiols are potentially important chiral building blocks in synthetic chemistry and are more stable than their cis analogues. While the cis-arene dihydrodiols can be produced on a relatively large scale by fermentation, their trans isomers cannot. The principal aim of this work was to carry out studies in tandem to inform the development of the synthetic pathway to convert arene cis-dihydrodiols to their trans isomers by (a) the synthesis of organometallic intermediates and (b) investigation of their reactivity by means of kinetic and equilibrium studies. A number of analogues based on sevenmembered ring systems instead of six were also investigated as a comparison. The four-step synthetic route being investigated involved formation of a tricarbonyl iron complex of the arene cis-dihydrodiol substrate, followed by reaction in acid to form a carbocation intermediate. This cation complex is trapped stereoselectively using hydroxide to give a trans isomer and decomplexation to remove the iron tricarbonyl moiety is the final step. Two substrates were examined, 3-bromocyclohexa-3,5-diene-1,2-diol and 3-trifluoromethylcyclohexa-3,5-diene-1,2-diol. The first three steps in the route were successfully performed on each compound in yields of 52 % and 43 % overall for the 3-bromo and 3-trifluoromethyl starting materials respectively. The final decomplexation step was not successful
however and will require optimisation of the conditions. The ionisation of the
tricarbonyl iron cis-dihydrodiol intermediates was investigated kinetically in strong acid, and the corresponding rate constant for the bromo substituted complex was determined to be 8.0 x 10-8 M-1 s-1 showing a significant lack of reactivity towards cation complex formation. This is expected based on previous work that reports low reactivity towards ionisation for any complexes that have hydroxyl groups endo to the iron centre, as is the case here. The reverse reaction, hydrolysis of the bromo-substituted cation, was too fast to measure but a pKR of 0.5 was estimated.

DOI

https://doi.org/10.21427/D77P55

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Document Type

Master thesis