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Axially chiral enamides : rotation barriers, substituent effects, and cyclisation reactions
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Phillips, Jessica M. (2017) Axially chiral enamides : rotation barriers, substituent effects, and cyclisation reactions. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3162970~S15
Abstract
The work presented in this thesis focuses on the synthesis, analysis and cyclisations of a series of N-halobenzylcycloalkenamides. Chapter 1 provides an introduction to atropisomerism, radical cyclisation and Heck cyclisation, including developments in the reaction conditions for radical and Heck cyclisations. The use of atropisomers in synthesis, and particularly in cyclisation reactions, is also discussed.
Chapter 2 reports investigations into the effects of aryl, acyl and alkene substitution on the barrier to rotation about the N-alkenyl bond in a series of enamides. A range of enamides were synthesised and their barriers to rotation were investigated by 1H VT NMR, and where desirable, by racemisation of an enriched atropisomer. The highest barriers to rotation were obtained with tetrasubstituted enamides, although additional bulk adjacent to the double bond (such as in tetralone-based compounds) was found to increase the barrier to rotation to a lesser degree. A precursor analogue to the natural product norchelidonine was also synthesised and was found to have a barrier to rotation between 20 and 24 kcal/mol.
Chapter 3 describes the results of Bu3SnH-mediated radical cyclisation of the enamides synthesised in Chapter 2. A range of cyclised products was obtained in most cases, resulting from either the 5-exo pathway or the 6-endo pathway, although the 6-endo pathway was found to predominate in almost all cases. Cyclisations of enamides with higher barriers to rotation proved more difficult, and indeed it was not possible to cyclise some of them, such as the precursor to the natural product norchelidonine. Chiral transfer should be possible with at least one α,α’,α’-substituted enamide, under the conditions used in this chapter.
Chapter 4 describes attempts to find a viable alternative method for the cyclisation of the enamides synthesised in Chapter 2, to combat the many disadvantages of the tin method. Samarium diiodide radical cyclisation and palladium Heck cyclisation of the simplest substrate were both successful. Samarium cyclisation generated the same products as tin cyclisation, in a slightly different ratio due to the difference in reaction conditions. Palladium Heck cyclisation gave only 5-exo cyclisation products: the direct product and the isomerised product, in varying ratios depending on the conditions used. The palladium Heck reaction conditions were then optimised for these compounds, and the optimised conditions were used to cyclise a selection of the compounds from Chapter 2.
| Item Type: | Thesis or Dissertation (PhD) | ||||
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| Subjects: | Q Science > QD Chemistry | ||||
| Library of Congress Subject Headings (LCSH): | Amides -- Synthesis, Ring formation (Chemistry), Chemistry, Organic | ||||
| Official Date: | September 2017 | ||||
| Dates: |
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| Institution: | University of Warwick | ||||
| Theses Department: | Department of Chemistry | ||||
| Thesis Type: | PhD | ||||
| Publication Status: | Unpublished | ||||
| Supervisor(s)/Advisor: | Clark, Andrew J. | ||||
| Extent: | xv, 199 leaves : charts | ||||
| Language: | eng |
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