Synthesis and Application of Chiral AraBOX ligands for Asymmetric Catalysis

Kellehan, David
This thesis deals with the design, synthesis and reactivity of novel 4,4'-bisoxazoline ligands and their metal complexes; (S,S)-MePrAraBOX, (S,S)-PhPrAraBOX, (S,R)-MePrAraBOX, (S,R)-PhPrAraBOX, (S,R)-BnOAcAraBOX and (S,R)-BnOHAraBOX. Metal complexes of these ligands have been applied to transition metal catalysed asymmetric reactions, in particular asymmetric Diels Alder, cyclopropanation and allylic alkylation reactions. A copper(II) complex of (S,R)-PhPrAraBOX catalysed a benchmark Diels Alder reaction in up to 57% ee, the highest enantioselectivity yet achieved for a 4,4'-BOX ligand in a Diels Alder reaction. An ee of 70% was achieved with a copper(I) complex of (S,S)-MePrAraBOX in a benchmark asymmetric cyclopropanation reaction, which is also the highest enantioselectivity yet achieved for a 4,4'-BOX ligand in these reactions. The ligands were also applied to the asymmetric allylic alkylation reaction. They were the first 4,4'-BOX ligands to generate enantiocontrol in the reaction, with a palladium complex of (S,S)-MePrAraBOX producing an ee of 72%. The rationalisation of these results, in particular the results relating to the cyclopropanation reaction, are supported by computational studies carried out by colleagues in Zaragoza. The 4,4'-bisoxazoline ligands (S,R)-BnOAcAraBOX and (S,R)-BnOHAraBOX, which contain secondary binding sites, were applied to the Diels Alder and asymmetric allylic alkylation reactions with low activity and selectivity. Ligand (S,R)-BnOHAraBOX was also applied to an asymmetric alkylation of benzaldehyde, showing low conversion and no selectivity. Chapter One deals with the introduction of the general concepts of asymmetric synthesis and asymmetric catalysis. Chapter Two discusses the synthesis of the 4,4'-bisoxazoline ligands and the application of the metal complexes of these ligands to the asymmetric reactions. Chapter Three contains the full experimental details for the project, including spectral and analytical data.
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Attribution-NonCommercial-NoDerivs 3.0 Ireland