Ph.D. / The work described in this thesis was directed at advancing the applications of Al(OTf)3, a metal triflate, in organic synthesis. Lewis acids play an important role in catalysis and catalyse reactions with high selectivities, unique reactivities under mild conditions. Metal triflates have become the Lewis acids of choice for acid catalysed organic transformations. A detailed literature study of metal triflates provided numerous examples of their use in organic transformations. Al(OTf)3 has been widely neglected as a Lewis acid which is contrasting to the attention the other metal triflates have received. Previous work in our laboratories had established Al(OTf)3 as an effective Lewis acid catalyst for the ring-opening of epoxides with simple alcohols and amines. The alcoholysis of epoxides provides a ready access to β-alkoxy alcohols. Whilst this reaction has been shown to occur with Al(OTf)3 as a catalyst, the established protocol calls for the use of the nucleophilic alcohol in an excess amount. Whilst this proves no problem when simple alcohols are employed as nucleophiles in the ring-opening reaction, it is a problem when more complex and expensive alcoholic nucleophiles are utilised. A modified procedure utilising Al(OTf)3 as a catalyst was developed which tolerates the use of only 1 equivalent of the nucleophilic alcohol for the ring opening reaction. The desymmetrisation of a meso-epoxide with chiral alcoholic nucleophiles was also investigated and the outcome of the diastereoselectivity of the reaction reported. The aminolysis of epoxides has been established utilising Al(OTf)3 as the Lewis acid catalyst. However, this has only been demonstrated for the ring opening of simple epoxides with simple amines. Piperazine derived β-amino alcohols with known biological activity were chosen as substrates with which to test the Al(OTf)3 catalysed aminolysis of epoxides in the synthesis of more complex β-amino alcohols. The various starting epoxides and amine nucleophiles were synthesised. During which a new approach towards the synthesis of - glycidyl amines was developed utilising a two step approach with the first step being catalysed by Al(OTf)3. It was also found that the optimal method for forming the β-amino alcohol bond was one in which the glycidyl motif was placed on the less basic heteroatom and ring opened by the more nucleophilic piperazine amine.

Ph.D. / The research described in this thesis was directed at advancing the application of metal triflates, Al(OTf)3 in particular, in organic synthesis, on the one hand and to contribute to the understanding of the underlying basis for their catalytic activity. The study was undertaken against the background and on the bases of a detailed literature study of metal triflates, their chemical and catalytic properties and applications thereof. Amongst others, it deals with the possible role of metal-bound water that give rise to Brønsted type acidity and that this induced Brønsted acidity may be responsible for the catalytic activity that is observed. The study was prompted by the realisation that Al(OTf)3 was largely neglected as a potential reusable catalyst. This is in marked contrast to the attention paid to other metal triflates, the rare earth metals in particular. Earlier work in this laboratory has shown that Al(OTf)3 is stable in water from which it can be recovered easily for reuse. In addition it showed promise as a Lewis acid catalyst and is relatively soluble in several organic solvents. New applications for the use of Al(OTf)3 have now been demonstrated. These include the efficient formation of acetals from aldehydes and ketones. The conversions can be carried out in an alcohol/orthoester mixture or preferably in neat orthoester. Other metal triflates, notably Sc(OTf)3 and In(OTf)3, are useful alternative catalysts. Al(OTf)3 can be easily recycled without loss of activity. This methodology also can be applied to aldehydes and ketones containing TBDMS groups without effecting deprotection of the ethers. In view of the sensitivity of the TBDMS groups to hydrolysis in the presence of triflic acid the results suggest little hydrolysis (or alcoholysis) of the metal triflates in the protic solvents used, which would generate trifluoromethanesulfonic acid as a consequence of such metal based hydrolysis. Al(OTf)3 was also found to be a good catalyst for the formation of THP ethers. It proved to be excellent for Friedel Crafts reactions using alkynes as substrates. Al(OTf)3 together with other triflates offers a mild alternative to the more traditional water sensitive Lewis acids, e.g. BF3, AlCl3 and TiCl4, which are difficult to recover and require the use of extremely dry solvents.

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