The Synthesis and Application of P,N Ligands in Asymmetric Catalysis

The synthesis of enantiomerically pure compounds and the methods by which this can be achieved is an area of huge interest within modern organic chemistry. Asymmetric catalysis, whether it be transition metal catalysis or organocatalysis, is one of the most common ways of synthesising enantioenriched compounds, and some of these methods are discussed in detail within this thesis. Within the Guiry group much knowledge exists relating to the synthesis of chiral P,N ligands and their application in asymmetric catalysis. Based on the previously synthesised P,N ligand; (S,S,Ra)-UCD-Phim, a library of centrally chiral ligands with an imidazoline backbone are synthesised herein. These ligands were then applied in catalysis and results obtained using them could be used to analyse the benefits of different sterics and electronics on an asymmetric reaction. UCD-Phim had previously been shown to be an effect ligand in the A3 coupling reaction, so the library of ligands prepared in the present study was initially applied in this reaction affording excellent enantioselectivities of 67-94% ee. However, it was found that the yields were much more variable (4-94%) suggesting axial chirality may be key to obtaining good reactivity in this reaction as exemplified with UCD-Phim.One of the main drawbacks that exists to the use of axially chiral ligands is that above a certain temperature the barrier to rotation will be overcome and epimerisation will occur, and with UCD-Phim this happens at temperatures above 40 °C. To display the utility of the centrally chiral ligands they were therefore applied to a high temperature syn-arylnickelative cyclisation reaction. The current work describes the first enantioselective version of this reaction with ee’s of up to 66% and yields of up to iv 42%. The substrate scope of the racemic reaction was also expanded upon to include ketones and imines. Finally, the utility of UCD-Phim was expanded to show that it is an effective ligand in the asymmetric alkynylation of quinolones giving yields of up to 92% and enantioselectivities of up to 97% ee. The applicability of the reaction was proven through scale up and synthesis of the natural products (+)- cuspareine and (+)-galipinine.