The use of functionalised lithium amides in the total synthesis of alkaloids

Lee, JA

Oxford Thesis Collection

Thesis

The use of functionalised lithium amides in the total synthesis of alkaloids

Abstract:: 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.

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APA Style

Lee, J. A. (2012). The use of functionalised lithium amides in the total synthesis of alkaloids [PhD thesis]. University of Oxford.

MLA Style

Lee, JA. The Use of Functionalised Lithium Amides in the Total Synthesis of Alkaloids. 2012. University of Oxford, PhD thesis.

Chicago Style

Lee, JA. 2012. “The Use of Functionalised Lithium Amides in the Total Synthesis of Alkaloids.” PhD thesis, University of Oxford.
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