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Theses, Masters


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Successfully submitted for the award of Master of Philosophy to the Technological University Dublin in 2008.


Abstract In this thesis, a viable route for conversion of arene cis-dihydrodiols to their trans isomers was investigated. The cis-dihydrodiols can be produced by large scale fermentation but their trans analogues are not accessible using this approach. The trans dihydrodiols are potentially important chiral building blocks in synthetic chemistry particularly because they have the advantage that they are more stable than the cis-isomers. The principal aim of this work was to carry out parallel studies to inform the development of the synthetic pathway under study by; (a) synthesis of organometallic and organic intermediates and products and, (b) investigation of the intermediates in the synthetic pathway under examination using kinetic and equilibrium studies. In the four step route being examined, the tricarbonyliron complex of an arene cis-dihydrodiol is formed and is reacted with acid to give a carbocation intermediate. This cation complex is then trapped stereoselectively by a nucleophile to afford the trans product. Decomplexation to remove the tricarbonyliron moiety is the final step. The isomerisation was carried out on cis-5,6-dimethoxycyclohexa-1,3-diene affording the trans-product in an overall yield of 31% for the four steps. In this case, the corresponding diol was too unstable to use as a starting material and thus the hydroxy substituents were converted to their methyl ethers. A trifluoromethyl and a bromo substituted dihydrodiol were each coordinated to tricarbonyliron by reaction with diironnonacarbonyl in yields ranging from 69 to 90%. The synthetic intermediate examined in most detail was the cation complex, (h5-6-methoxycyclohexadien-1-yl)tricarbonyliron, which was formed from the corresponding (h4-cis-5,6-dimethoxycyclohexa-1,3-diene)tricarbonyliron complex. Rate constants for ionisation of this dimethoxy complex to form the coordinated methoxycyclohexadienyl cation were measured. The nucleophilic reaction of the cation complex with water to form (h4-trans-5-hydroxy-6-methoxycyclohexa-1,3-diene)tricarbonyliron and conversion of this trans complex back to the cation were also studied, allowing a pH-profile (log k versus pH) to be constructed. An equilibrium constant, pKR, = 2.80 for the coordinated methoxycyclohexadienyl cation [R+] was determined kinetically from measurements of the rate constants for hydrolysis of the cationic species and for the ionisation of the corresponding coordinated trans-5-hydroxy-6-methoxy substituted complex [ROH]. A comparison of the rate constants measured in this work for ionisation of the endo- and exo- (i.e. cis and trans) tricarbonyliron complexes serves as a useful model for comparison to the endo and exo isomers of other tricarbonyliron complexes. It was reported by Johnson and co-workers that the coordinated exo complexes formed faster than the endo complexes but that they do not differ significantly in stability. Therefore, it can be concluded that the exo products have a lower kinetic barrier to reaction. The equilibrium constant determined for formation of the coordinated trans-5-hydroxy-6-methoxycyclohexadiene complex from its corresponding cation can be compared with other coordinated and uncoordinated hydroxy and methoxy substituted cyclohexadienes previously examined. It was found that the tricarbonyliron moiety displays a rate retarding effect on the coordinated cation species and that these cations are less reactive than the uncomplexed species. Also, it was evident that the β-methoxy substituent has a destabilising effect (δ= 1.7) on the cation complex. This effect is also observed when rate constants for formation of the cations were compared as the complex with the β-methoxy substituent reacts approximately 64 times more slowly than a complex lacking a β-methoxy substituent. The difference between the hydroxyl and methoxy substituents was found not to have a significant impact on reactivity. It can be concluded that ionisation of the coordinated endo (i.e. cis-) diol to form the corresponding cation is the difficult step in the route to convert arene cis-dihydrodiols to their trans isomers. The final decomplexation step also requires some optimisation of the synthetic conditions.


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