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Organoaluminum Mediated Interrupted Nazarov Reaction

  • Author / Creator
    Kwon, Yonghoon
  • Five-membered carbocycles are highly prevalent motifs in natural products and pharmaceutical drugs. Finding routes towards these moieties has been an attractive area of pursuit in synthetic organic chemistry. The Nazarov reaction is one that has been widely used to access cyclopentenone compounds. Interrupting the Nazarov reaction intermediate from its typical pathway has also emerged as a valuable tool to synthesize highly functionalized cyclopentanones. This dissertation contributes to expand the scope of the interrupted Nazarov reaction and hopefully opens door for the synthesis of 6-membered carbocycles and 1,4-diketones beyond functionalizing 5-membered carbocycles. Recent developments in the interrupted Nazarov reaction are summarized in Chapter 1. The strategy of trapping Nazarov intermediates using heteroatom and π-nucleophiles in both an inter- and intramolecular fashion provides increased molecular complexity with enhanced step economy. Chapter 2 describes the first example of a Nazarov reaction mediated by triorganoaluminum reagents. Use of these organoaluminum compounds allowed incorporation of simple alkyl and phenyl groups, as well as cyano and azido moieties. Details of using diethyl zinc as a trapping reagent in the Nazarov reaction are also discussed as a comparison to the organoaluminum reactions. Efforts to find alternative Nazarov substrates involving the use of organoaluminum reagents were also carried out. A divinyl carbinol was found to undergo a domino Oppenauer oxidation/Nazarov cyclization. During the study of the organoaluminum mediated interrupted Nazarov reaction, unexpected α-hydroxy cyclopentanones were formed upon unintentional exposure to atmospheric oxygen. Chapter 3 provides details of the aluminum enolate oxidation and its tactical use in the Nazarov cyclization. The oxygen-trapping event in the Nazarov reaction was a realization of double interrupted Nazarov reaction: a nucleophilic addition followed by the resulting enolate addition to an electrophile. Inspired by the double functionalization, we hunted for other interesting electrophiles. Chapter 4 tells the story of these multi-component organoaluminum interrupted Nazarov reactions using masked aldehydes and carbenoids. Chapter 5 describes the oxidative interruption of the Nazarov reaction. The use of potassium permanganate enabled the synthesis of syn 1,4-diketones via a decarbonylative decomposition of the Nazarov oxyallyl intermediate. Preliminary results of diatomic chlorination and bromination of the oxyallyl cation intermediate are also included in this chapter.

  • Subjects / Keywords
  • Graduation date
    2015-06
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3C24QS9T
  • 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, Frederick (Chemistry)
  • Examining committee members and their departments
    • Hall, Dennis (Chemistry)
    • Batey, Robert (Chemistry)
    • Stryker, Jeffrey (Chemistry)
    • Serpe, Michael (Chemistry)