KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    A Combined Allylic Azide Rearrangement and Intramolecular Schmidt Reaction - Discovery, Development, and Application

    Thumbnail
    View/Open
    Liu_ku_0099D_12528_DATA_1.pdf (17.12Mb)
    Issue Date
    2012-12-31
    Author
    Liu, Ruzhang
    Publisher
    University of Kansas
    Format
    503 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Medicinal Chemistry
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
    Metadata
    Show full item record
    Abstract
    The research presented herein describes synthetic applications of an allylic azide rearrangement, mainly focusing on its combination with the intramolecular Schmidt reaction to afford vinyl-substituted bicyclic lactams. Undesired stereochemistry was obtained in the initial synthetic route to an advanced intermediate of natural product pinnaic acid, in which a home-made electrochemistry apparatus was involved in the key step to modify the tricyclic lactam. The combination of allylic azide rearrangement and intramolecular Schmidt reaction afforded the target with desired stereochemistry, and the synthesis of the cyclobutanone was achieved by an asymmetric [2+2] cycloaddition. Prior to its combination with the intramolecular Schmidt reaction, the rearrangement of allylic azides was studied from different perspectives such as substrate, time, temperature, and Lewis acid. Next, the combined reaction was studied with the cyclohexanone-based allylic azide, whose stereochemical outcomes were rationalized by the conformational analysis and computational calculations. Different substituents on the cyclic ketone ring system were found to have different impacts on the diastereoselectivity. During this process, a chloro-Prins reaction was found as the major side-reaction, and carbocation-mediated allylic azide rearrangement was confirmed. Dihedral angle was utilized to explain why and in which cases the six-membered intermediate proceeds through chair or boat conformation for fused bicyclic system. This reaction was also utilized to produce twisted amides via cation-π interaction, along with the use of other by-products from different Lewis acids. The utilization of this methodology to finish the total synthesis of alkaloid 205B is underway. Initial studies of the combination of allylic azide rearrangement and alkyne-azide cycloaddition were conducted. Also the reorganization of allylic azides was utilized to generate 2-azadiene species, which may undergo Diels-Alder reactions or electrocyclizations.
    URI
    http://hdl.handle.net/1808/14830
    Collections
    • Medicinal Chemistry Dissertations and Theses [81]
    • Dissertations [4473]

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps