Seven- and Eight-Membered Ether Formation via Sulfonium Ylide Rearrangement Processes and Application in an Approach to (+)-Laurencin

  • Author / Creator
    Cao, Liya
  • Given the large number of biologically active natural products containing medium-sized ether motifs, many organic chemists have shown great interest for developing new methodologies to access these structures. In particular, numerous synthetic methodologies for the construction of seven-membered and eight-membered ethers have been developed by research groups around the world. Recent advances in the synthesis of seven-membered and eight-membered ethers will be reviewed in chapter one. This chapter will cover some of the more notable publications from the last five years (from 2005 to 2009). In chapter two, the development of ring expansion reactions via [1,2]-shift rearrangements of thioacetal-derived sulfonium ylides will be described. A variety of functionalized diazoketones and diazoketoesters were made from commercially available starting materials. Sulfur-bridged seven-membered and eight-membered ethers were constructed upon treatment of these diazo precursors with suitable metal catalysts. It was found that Rh2(OAc)4 was a better catalyst for diazoketones, while Cu(hfacac)2 proved to be more effective for diazoketoesters. This methodology provides a convenient route to the seven- and eight-membered ethers in relatively few steps. In chapter three, the methodology for construction of sulfur-bridged ethers was employed as the key step in the attempted formal synthesis of (+)-laurencin. In this approach, the relative and absolute stereochemistry was established by a highly enantioselective and diastereoselective allylboration, a facially selective Michael addition, and a thermodynamically controlled acetal formation. The eight-membered sulfur-bridged ether was efficiently constructed using our [1,2]-shift reaction of a sulfonium ylide in toluene at 100 oC in the presence of Cu(hfacac)2. The following desulfurization and decarboxylation was effective at affording an advanced intermediate in this synthesis. The chemistry demonstrated in this chapter outlines a promising strategy for the formal synthesis of (+)-laurencin.

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  • Graduation date
  • Type of Item
  • Degree
    Doctor of Philosophy
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    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
    • Department of Chemistry
  • Supervisor / co-supervisor and their department(s)
    • Frederick G. West (Department of Chemistry)
  • Examining committee members and their departments
    • John M. Seubert (Pharmaceutical Sciences)
    • Liang Li (Department of Chemistry)
    • Jon D. Rainier (Organic Chemistry, University of Utah)
    • Christopher W. Cairo (Department of Chemistry)
    • Dennis Hall (Department of Chemistry)