Enantioselective alkylation reactions using silylamide as brønsted probase
Date of Issue2016
School of Physical and Mathematical Sciences
In most of the asymmetric phase transfer reactions, Brønsted bases are involved and the inorganic bases used can greatly influence the profile of the reaction. A brief introduction of the recent developments in asymmetric phase transfer catalysis is presented in the first chapter of this thesis. Alkoxide salts are able to activate substrates with high pKa values but the occurrence of side reactions is unavoidable. On the other hand, carbonate and phosphate salts are milder but their low basicity limits the scope of their reactions. This presents a difficult situation in which sensitive substrates, such as lactone, are easily hydrolyzed in the presence of a strong base, but unreactive when a weaker base is used. In order to circumvent this issue, a Brønsted probase strategy, which involves the in situ generation of a strong base from silylamide (probase) through the use of fluoride, is hence devised. In this approach, the strong base produced is a transient species and does not exist in excess, thus, reducing background and side reactions. Herein, an introduction to the background and recent development in asymmetric phase transfer catalysis and asymmetric catalytic Brønsted base reactions is first presented, which forms the basis for our proposed research design. We demonstrate that when pentanidinium and bisguanidinium are used as catalysts, highly enantioselective phase transfer alkylation of dihydrocoumarin (lactone) can be achieved, and the results are presented in Chapter 2. In the next chapter, this Brønsted probase strategy is further extended to cyclic and linear ketone substrates. Consolidating the results achieved in the preceding chapters, control experiments were conducted to investigate the mechanism of our strategy, with the results presented in Chapter 4. These experiments prove that hypervalent silicates form ion-pair intermediates with pentanidinium and bisguanidinium in the reaction, and it is through these ion-pairs that the selective enantiofacial approach of the electrophiles is determined.