Studies on the Phospho-Aldol Reaction Catalysed by Aluminium Salcyan and Related Complexes

The phospho-aldol (PA) reaction is one of the most versatile reactions for the formation of phosphorus-carbon [P-C] bonds. The reaction is a base-catalysed addition reaction between a hydrogen-phosphonate ester and a carbonyl substrate, affording alpha-functionalised phosphonate esters. These PA products have found a wide-spread application in biomedical science.

Since the PA reaction is capable of affording products with new stereocentres, considerable effort has been devoted over the last few decades to developing asymmetric catalytic variants of the PA reaction. Through the manipulation of the substituent groups of the salcyan ligands there is the possibility of controlling the enantioselectivity and stereochemical outcome of the reaction.

This thesis describes previous work that has been carried out with regards to the PA reaction, how it works, Schiff base complexes and how aluminium can be incorporated in a Schiff base complex, ultimately resulting in the catalysis of the PA reaction. Discussed are the studies carried out towards the construction of chiral aluminium complexes based on the (R,R)- N4-salcyan framework for application as catalyst precursors for the asymmetric phospho-aldol reaction.

A computational study focusing on the complex {[(R,R)-salcyan(tBu)2]Al(μ-OH)}2 as part of a validation study carried out on Gaussian 03 is outlined. The results were used to validate the original molecular modelling studies that used semi-empirical methods. In addition, geometry optimisation calculations were carried out on a selection of single crystal X-ray structures as a means of identifying the most basic site of the complex and therefore determine where deprotonation of DMHP could take place.

To conclude this thesis two relatively new areas for PA catalysis are discussed. One such area focuses on the incorporation of cyclams into the salcyen backbone, which could serve as a versatile framework for PA catalysts with the inclusion of a secondary basic functionality. The second area introduces phosphine oxide and phosphine substituted N2O2 salcyan compounds, which can provide a basic complex construction with the added advantage of being able to introduce suitable co-factors, tuneable to a specific substrate. This approach would open up the chance of parallel processing and analysis.