Solid phase organic synthesis is a powerful technique to facilitate rapid synthesis and easy purification of organic compounds. The advancement of linkers and cleavage strategies is of paramount importance for the success of this approach. This thesis is concerned with the development of a robust safety catch linker system aimed to allow a broad range of commonly used reagents to be employed in a synthetic sequence carried out on a solid support. Chapter 1 outlines the principles of solid phase organic synthesis, the terminology associated with this approach and the advantages and disadvantages compared to conventional solution phase methods. Common attachment and release strategies for various functional groups are described and the safety catch principle is introduced. Chapter 2 discusses the design features of the linker system. Proof of principle is demonstrated for the attachment and release strategies with a simple solution phase model system. Chapter 3 describes the adaptation of the linker system to the solid phase. Key transformations are modelled with solution phase experiments and subsequently applied to solid phase. The loading determination of the solid phase system is also described. Chapter 4 reports an assessment of the reactivity of the linker system in the coupling transformation of aliphatic alcohols and amines. The chemoselectivity and efficiency of the CAN debenzylation/cyclorelease protocol is also evaluated. Chapter 5 demonstrates the utility of the linker system with the optimisation of a simple synthetic sequence in solution followed by adaptation to the solid phase. The synthesis of a pilot library of aryl alcohols utilizing a Suzuki coupling on solid support is described. The attachment and release of amines is also demonstrated with solid phase examples. Chapter 6 examines the potential of the linker system as an analytical tool to assess the outcome of stereoselective transformations. A chiral auxiliary is attached to the solid phase by aid of the safety catch linker and released into solution. A solution phase model system is developed to aid preliminary investigations in solution prior to adaptation to the solid phase.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:414228 |
| Date | January 2005 |
| Creators | Skarpheđinsson, Hjalmar |
| Contributors | Davies, Stephen G. |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:68179292-c0b4-438c-9c25-d60bfcce907f |
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