The design and synthesis of a novel series of chiral catalysts

• Main Author: Grant, Richard
• Published: University of Edinburgh 2001
• Subjects: 541.39
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.651709

The last twenty years have witnessed a great increase in the discovery and development of chiral reagents for application in asymmetric synthesis. The aim of this project was to develop a novel series of chiral ligands from inexpensive materials, and to assess their potential as chiral catalysts in asymmetric synthesis. This was to be achieved through the exploitation of the chirality of the biphenanthryl system. A pre-existing route into such asymmetrically substituted biphenanthryl systems was optimised to give racemic quantities of 10'-hydroxy-9,9'-biphenanthryl-10-carboxyaldehyde. Resolution of this racemate was achieved through the formation of a diastereoisomeric hydrazone with S-AMP. Chirally pure 10'-hydroxy-9,9'-biphenanthryl-10-carboxaldehyde was used as the starting point for the generation of a series of chiral catalysis. Four bi-dentate biphenanthryl ligands were developed and applied in asymmetric synthesis. A chiral hydrazone, oxime and <i>tert</i>-amine were applied in the asymmetric addition of diethylzinc to aldehydes. A primary amine was synthesised and applied in the enantioselective borane reduction of pro-chiral ketones. Chiral GC analysis of the modified substrates from these reactions was carried out by Avecia. Finally, attempts were made to modify the chiral biphenanthryl moiety towards the synthesis of a chiral dihydropyridine reagent. This system was hoped to mimic the co-enzyme NADH.