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Exploring New Aspects of the Nazarov Cyclization

  • Author / Creator
    Wu, Yen-Ku
  • The five-membered carbocyclic framework is a prevailing structural motif found in natural products and bioactive compounds. Over the years, the Nazarov reaction has been continuously refined as a versatile protocol to access cyclopentanoid products. In this dissertation, several projects built on Nazarov chemistry will be detailed. Recent research activities regarding umpolung reactivity at the carbonyl α-carbon, a relatively underemphasized carbonyl umpolung, is discussed in Chapter 1. The cationic intermediates generated during the Nazarov cyclization have been shown to participate in domino or cascade sequences, thus providing a convenient entry to expeditiously increase molecular complexity from relatively simple precursors. Chapter 2 describes a comprehensive investigation of new bond-forming reactions initiated by the Nazarov reaction wherein umpolung reactivity at the α-carbon of cyclopentanones was achieved through the interception of 2-oxidocyclopentenyl cations derived from the initial electrocyclization with an array of carbon nucleophiles. Alternative substrates to the key pentadienyl cation intermediate in the Nazarov reaction, potentially offering access to unconventional substitution patterns or milder conditions, have recently attracted considerable interest. Chapter 3 discusses the use of vinyl silyloxyallenes, which function as dienone surrogates through Brønsted acid activation, to effect the Nazarov cyclization. Additionally, a novel extension of the vinyl allene version of the Nazarov reaction, involving an interrupted Nazarov reaction employing pendent aromatic traps will be presented. Chapter 4 recounts a novel, two-step, modular synthesis of α-amidoindanones. This process is based upon the Nazarov cyclization of 2-amido-1,4-pentadien-3-ones that were in turn prepared via a novel coupling process between α,β-unsaturated aldehydes and an α-lithiated allenamide. As supported by a deuterium labelling study, the mechanism of the coupling entails sequential carbonyl addition and 1,3-sigmatropic rearrangement.

  • Subjects / Keywords
  • Graduation date
    2013-06
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3J960H1D
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Department of Chemistry
  • Supervisor / co-supervisor and their department(s)
    • West, F. G. (Chemistry)
  • Examining committee members and their departments
    • Clive, Derrick L. J. (Chemistry)
    • MacMillan, Andrew M. (Biochemistry)
    • Lowary, Todd L. (Chemistry)
    • Suzuki, Keisuke (Chemistry, Tokyo Institute of Technology)
    • Campbell, Robert E. (Chemistry)