Abstract
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.