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The selective immobilisation of chiral intermediates in asymmetric synthesis. / Rosemary Anne Dignan
Swansea University Author: Rosemary Anne Dignan
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The advantage of solid phase synthesis is that the products can be isolated and purified simply by filtration. However, the reaction conditions required often lead to different kinetic behaviour, differences in reactivity and solvation and other problems, not encountered in solution phase reactions....
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The advantage of solid phase synthesis is that the products can be isolated and purified simply by filtration. However, the reaction conditions required often lead to different kinetic behaviour, differences in reactivity and solvation and other problems, not encountered in solution phase reactions. This thesis describes an approach at utilising the ease of purification associated with solid-phase synthesis without encountering the problems associated with two-phase reaction systems. It was achieved by selectively immobilising a bipyridyl-tagged chiral auxiliary and a bipyridyl-tagged oxazaborolidine catalyst by interaction by with a resin-bound transition metal upon completion of the solution-phase reaction. Chapter one is a literature review detailing some of the different approaches that have been reported in exploiting the benefits of solid-phase purifications whilst avoiding the associated problems. Soluble polymeric supports, fluorous labelling and some more unusual methods are investigated. Chapter two is a general introduction to how chiral auxiliaries can stereochemically influence reactions. Chiral auxiliary mediated alkylations, aldol reactions, conjugate additions and Diels-Alder reactions are focussed on. Chapter three details the complete synthesis of (R,R)-4,4'-bis-[1-(4,5-diphenyl-3-propionyl-imidazolidinonyl)-N-methyl]-2,2'-bipyridine, a bipyridyl-tagged chiral auxiliary. An investigation into its ability to reversibly bind to a resin-bound transition metal is then reported. Chapter four describes the extensive study on the reactivity of the tagged chiral auxiliary, concentrating on chiral alkylations, halogenations and aldol reactions. Chapter five is an account of how the selective immobilisation approach was extended to include chiral oxazaborolidine catalysts. A general introduction to oxazaborolidine catalysts is provided. The total synthesis of the bipyridyl-tagged oxazaborolidine, (S,S)-4,4'-bis-[4-(2-amino-3-hydroxy-3,3-diphenyl-propyl)phenoxymethyl]-2,2'-bipyridine is reported and the investigation into its ability to reversibly bind to a resin- bound transition metal is described. The chiral reduction of acetophenone using the tagged catalyst and the subsequent recovery of the catalyst is then explored.
Faculty of Science and Engineering