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Title: Axially chiral enamides : rotation barriers, substituent effects, and cyclisation reactions
Author: Phillips, Jessica M.
ISNI:       0000 0004 7227 5943
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2017
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD Chemistry