Approaches to selective phosphoryl transfer

• Main Author: Simmons, Jonathan
• Other Authors: Jones, Simon
• Published: University of Sheffield 2017
• Subjects: 540
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.733618

The work in this thesis describes the approaches made to produce a method for selective phosphorylation of alcohol substrates. Development of work into the asymmetric phosphorylation using N-phosphoryl oxazolidinones enabled a model to be proposed which accounted for the selectivity of these reactions, in which a combination of relay effects generate a transient chiral environment, this with the formation of diastereomeric reactive species and steric interactions between adjacent alkoxide moieties accounts for these selectivities. Modifications of the phosphoryl moiety were proposed from this model to improve the low selectivities of the N-phosphoryl oxazolidinone chiral auxiliaries, but no enhancement could be made due to a drop in reactivity when larger groups were incorporated. A new proposal of using P-chiral auxiliaries was implemented to enhance the selectivity without affecting the reactivity. A new P-chiral oxazolidinone synthesis was optimised and reacted under the standard conditions. The selectivity of one diastereoisomer gave a 12% ee, similar to the selectivity of the N-phosphoryl oxazolidinones reinforcing the model proposed earlier whereas the other diastereoisomer with the larger group close to the stereodirecting group shut off the reactivity. This demonstrated that oxazolidinone chiral auxiliaries containing a stereodirecting group are not optimum and therefore the stereodirecting group was placed at the phosphate group. However a low selectivity similar to that of the other oxazolidinone was yielded. This research moved to produce a trifunctional phosphorylation catalyst. Podand and polyether based catalysts were synthesised and tested to prove that trifunctional catalysis was occurring in these phosphorylation systems and a model was proposed which accounts for this trifunctional rate enhancement. These will allow for future catalysts to be designed bearing stereodirecting groups.