Use this URL to cite or link to this record in EThOS:
Title: The synthesis of medium-sized ring containing libraries using oxidative fragmentation and rearrangement strategies
Author: Jones, Alan M.
ISNI:       0000 0004 2717 7906
Awarding Body: University of St Andrews
Current Institution: University of St Andrews
Date of Award: 2009
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
This thesis describes the development of a synthetic route that encodes a library of compounds containing medium-sized ring systems, with particular emphasis on the use of oxidative fragmentation and rearrangement strategies. Chapter 1 introduces diversity oriented synthesis (DOS) with particular emphasis on medium-sized ring synthesis and fragmentation/rearrangement protocols to achieve diversity. A more detailed discussion of oxidative fragmentation and rearrangement methods is also presented. Chapter 2 describes strategies for the synthesis of a collection of heterocyclic compounds known as diazabenz[e]aceanthrylenes. The scope of the reaction was explored as a function of a range of substituents and of the ring size of the N-aryl lactam that was used. Spectroscopic observations associated with this set of compounds are also discussed. Chapter 3 describes the development of an m-CPBA-mediated oxidative fragmentation of the diazabenz[e]aceanthrylenes. Analysis of the products from these reactions revealed the presence of atropisomerism due to restricted rotation about the N sp²-C(aryl) sp² bond. Chapter 4 focuses on a related example of oxidative fragmentation from the literature. A previously overlooked stereogenic axis is explored in this system using X-ray crystallographic analysis and variable temperature ¹H NMR spectroscopy. Reinterpretation of the reported mechanism-probing experiment led to the isolation of an alternative isomeric product and an improved interpretation for the reaction outcome is presented. Variable temperature ¹H NMR spectroscopic experiments revealed the energy barrier to racemisation in the medium-sized ring-containing analogues and based on this data the mode of ring inversion is discussed. Chapter 5 describes three rearrangements of the medium-sized ring system created in Chapter 3 including the formation of an azepinoindole ring structure, a Favorskii reaction and spiro-oxindole synthesis. A rationalisation for these reaction outcomes is included along with experimental support of mechanistic proposals. The generality and scope of the reactions are demonstrated including a nucleophile screen. Chapter 6 describes the synthesis of a library of 69 compounds consisting of examples of the core structures described in Chapters 2, 3 and 5. A discussion of the selection process and adaption of the protocol to parallel synthesis is presented. This chapter concludes with preliminary screening of the library against a variety of strains of yeasts and bacteria.
Supervisor: Westwood, Nicholas J. Sponsor: ical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Oxidative fragmentation ; Medium-sized rings ; Rearrangements ; Atropisomers ; Heterocycles