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Title: Carbohydrate-based N-heterocyclic carbenes for enantioselective catalysis
Author: Henderson, Alexander St. John
ISNI:       0000 0004 6059 7355
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2016
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The synthesis of carbohydrate-based N-heterocyclic carbene ligands for the Rh-catalysed asymmetric hydrosilylation of ketones has been explored. Initial studies utilised an alkylation approach to globally modify the hydroxyl functionality of a D-glucosamine scaffold. This strategy was amenable to a range of electrophiles; such as BnBr and Mel, which gave access to a library of amino-,β-glycosides. The corresponding C2- symmetric NRC.HCI salts could be synthesised from these amines, glyoxal and paraformaldehyde. Furthermore, upon deprotonation, the carbohydrate-based NRCs could be successfully ligated to [Rh(COD)Clh to give the Rh-NRC complexes. These catalysts were evaluated in a typical benchmark reaction; the hydrosilylation of acetophenone. Two factors were found to affect the er of the product alcohol (l-phenylethanol): (i) the use of apolar soLvents such as hexane, and, (ii) the size of the group modifying the carbohydrate's hydroxyls. For instance, the catalyst with the NRC ~ppendage derived from permethylated glucosamine gave the highest er (80:20). Next, the effect of varying the carbohydrate's stereochemistry at the C-1 and C-2 carbons on the hydrosilyhltion reaction was investigated. To this end, four catalysts with NRC ligands derived from α- and ,β-mannosamine and α- and ,β-glucosamine were synthesised. Interestingly, a departure from the ,β-glucosamine scaffold was detrimental to the obsetved er in the product alcohol. The all equatorial scaffold, at least across the C 1-3 positions of the carbohydrate, was crucial for asymmetric induction. Subsequently, the steric bias of the C-1 and C-3 positions was probed, given these carbons flank the C-2 attachment of the carbohydrate moiety to the NRC ligand. While glycosylation protocols gave access to C-1 ,β-thiophenyl-glucosides for NRC.HCI synthesis, derivatising the C-3 hydroxyl was more challenging. This resulted in the development of a method based on SNAr, which also led to several side investigations. The C-1 and C-3 sterically biased RhNRC complexes turned out to be pseudo-enantiomeric catalysts for the hydrosilylation of acetophenone, which gave the product alcohol in 30:70 and 86:14 er, respectively. Further optimisation of this ligand system was undertaken, however, the stereoselectivity could not be improved upon. Computational modelling was also performed in an attempt to probe the catalysts' method of asymmetric induction but this ultimately provided no additional insight. Finally, chelating carbohydrate-based NRC.HCI salts were synthesised. However, upon ligation to Rh,- the chelating functionality, a hydroxyl group, was found not to be bonded to the Rh-centre. While these complexes were active for the hydrosilylation of acetophenone, a negligible er was detected in the product alcohol. Further work is still required to fully evaluate this type of carbohydrate NRC ligand.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available