This thesis is concerned with the application of the conjugate addition of functionalised lithium amides in the asymmetric syntheses of (−)-morphine and all members of the homalium alkaloids. Chapter 1 introduces the conjugate addition reaction as an important bond forming reaction, and explores its utility in the asymmetric synthesis of a variety of natural products. The conjugate addition of secondary lithium amides derived from α-methylbenzylamine is discussed, along with its application to the asymmetric synthesis of alkaloids. Chapter 2 describes two distinct attempts towards the asymmetric synthesis of (−)-morphine, both reliant upon the lithium amide conjugate addition and an intramolecular Diels-Alder reaction to set the five required stereogenic centres. The use of the novel and highly functionalised reagent lithium (R)-N-[2′-(7-methoxybenzofuran-3-yl)ethyl]-N-(α-methylbenzyl)amide and its derivatives is reported. Chapter 3 focuses on the use of the novel reagent lithium (R)-N-(3-chloroprop-1-yl)-N-(α-methylbenzyl)amide and its derivatives in the asymmetric synthesis of two of the homalium alkaloids, (−)-(S,S)-homaline and (−)-(R,R)-hopromine, culminating in the most efficient syntheses of these alkaloids to date. Further, a sample of the (4′R,4′′S)-diastereoisomer of hopromine was synthesised, serving to confirm the proposed absolute configuration within natural (−)-(R,R)-hopromine. Chapter 4 extends the methodology developed in chapter 3 to the asymmetric synthesis of all possible diastereoisomers of the remaining homalium alkaloids, (−)-hopromalinol and (−)-hoprominol. These syntheses were used to propose the absolute configurations within these alkaloids, and therefore represented the first asymmetric syntheses of natural (−)-(4′S,4″R,2‴R)-hopromalinol and (−)-(R,R,R)-hoprominol. Chapter 5 contains full experimental procedures and characterisation data for all compounds synthesised in Chapters 2, 3 and 4.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:580976 |
| Date | January 2012 |
| Creators | Lee, James A. |
| 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:f558ce63-6b8d-4a9f-8f20-8b231d7a110e |
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