Interrupted Processes and Alternative Substrates for the Nazarov Cyclization

  • Author / Creator
    Fradette, Ryan J
  • This dissertation expands the scope and understanding of the Nazarov electrocyclization and interception of the reactive cyclopentenyl cation intermediate that is formed though a 4π electrocyclization of a pentadienyl cation. An intermolecular process for interrupting the Nazarov is discussed. Also, a new class of alternative substrates, and a new method of activation is presented. Recent advances in the area of Nazarov chemistry is summarized in Chapter 1. Interrupting the Nazarov reaction from its typical pathway by trapping the reactive cyclopentenyl cation with a nucleophile, or the enol(ate) intermediate with an electrophile enables rapid gains in molecular complexity. Alternative substrates and methods of activation can avoid some of the restrictions faced when using traditional acid activation of cross-conjugated ketones. Chapter 2 describes the Lewis acid mediated tandem Nazarov cyclization/intermolecular electrophilic aromatic substitution cascade. Our observations suggest that a diquinane is essential in establishing a cyclopentenyl cation that is sufficiently reactive and persistent to be trapped by the arene nucleophile. Importantly, complete regioselectivity and diastereofacial selectivity was observed for arene the trapping. An oxidation-initiated Nazarov cyclization of 1,4-pentadien-3-yl ethers was developed (Chapter 3). The DDQ oxidation of the 1,4-pentadien-3-yl ether substrates led to a reactive pentadienyl cation intermediate that successfully underwent Nazarov cyclization. The process was terminated by a highly regioselective elimination to generate cyclopentadienol ethers bearing an exo methylene. The exo elimination was notable, leaving the two new stereocenters formed in the stereospecific cyclization step untouched. A facile 1,3-transposition of allylic alcohols that was previously observed while preparing substrates for the vinylogous Nazarov reaction has been studied. We were able to expand the scope of this method to include a variety of tertiary propargylic bis(allylic) alcohols, tertiary propargylic allylic alcohols, tertiary bis(propargylic) allylic alcohols, and bis(allylic) cyanohydrins (Chapter 4). Additionally, the vanadium catalyzed transposition was carried out in tandem with a gold catalyzed cycloisomerization to generate tri-substituted furans.

  • Subjects / Keywords
  • Graduation date
    Fall 2014
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • 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
  • Institution
    University of Alberta
  • Degree level
  • Department
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Floreancig, Paul (Chemistry, University of Pittsburgh)
    • Vasanthan, Thava (Agricultural, Food & Nutritional Science)
    • Clive, Derrick (Chemistry)
    • Gibbs-Davis, Julianne (Chemistry)
    • Hall, Dennis (Chemistry)