Unconventional Substrates for the Nazarov and Imino-Nazarov Reactions

  • Author / Creator
    Bonderoff, Sara A
  • 5-Membered carbocycles are ubiquitous in natural products and synthetic drugs. Methods of generating them are therefore valuable, and the ability to do so in a stereospecific and enantioselective manner while making considerable gains in molecular complexity with additional incorporation of versatile handles for further elaboration are even more desirable. In the Nazarov reaction, activation of a dienone by a strong Brønsted or Lewis acid results in the formation of a conjugated pentadienyl cation, which can then undergo conrotatory 4π-electrocyclization to yield a cyclopentenone.
    Recent activity in the area of Nazarov chemistry is summarized in Chapter 1. Unconventional substrates are gaining popularity in the Nazarov field due to their potential to eliminate some of the restrictions faced when using the traditional substrates (divinyl ketones). Chapter 2 describes the preparation of 1-alkoxy-2,2-dichloro-1-vinylcyclopropanes, and their application to the Nazarov cyclization. These compounds undergo electrocyclic ring opening of the cyclopropane followed by Nazarov cyclization to furnish chlorinated 2-cyclopentenones. Importantly, this reaction could be done under catalysis by indium(III) chloride in leading examples. Arene traps were tethered through the akoxy-substituent in an effort to effect a novel mode of interrupted Nazarov reaction; however, this reaction was not realized.
    During the study of 1-alkoxy-2,2-dichloro-2-vinylcyclopropanes, an unexpected Friedel-Crafts cyclization was observed in some substrates. On further investigation of the process (Chapter 3), it was found that silver(I) bis(trifluoromethanesulfonyl)imide acts as a precatalyst in a Brønsted acid catalyzed intramolecular Friedel-Crafts alkylation of arenes with unactivated alkenes. Electron-rich and electron-deficient arenes as well as heteroaromatic rings reacted with alkenes to afford 5-,6-,7- and 8-membered rings, often generating a quaternary center adjacent to the arene.
    In stark contrast to the Nazarov reaction, there is very little knowledge about its nitrogen analogue, the imino-Nazarov reaction. In Chapter 4, our approach to the imino-Nazarov reaction of 1-amino-2,2-dichloro-1-vinylcyclopropanes is reported. The cyclization product is a cyclopenteniminium salt, which is reduced to furnish cis-3-amino-4-chlorocyclopentenes. This is the first example of an imino-Nazarov reaction with an electron-rich amine that is retained in the product. These substrates have also afforded the first interrupted imino-Nazarov reaction.

  • Subjects / Keywords
  • Graduation date
    Fall 2012
  • Type of Item
  • Degree
    Doctor of Philosophy
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  • 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.
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  • Institution
    University of Alberta
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  • Department
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Klobukowski, Mariusz (Chemistry)
    • Choi, Philip (Chemical and Materials Engineering)
    • Clive, Derrick (Chemistry)
    • Frontier, Alison (Chemistry)
    • Hall, Dennis (Chemistry)