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    Copper-Catalyzed Decarboxylative Trifluoromethylation Reactions

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    Issue Date
    2017-05-31
    Author
    Ambler, Brett R.
    Publisher
    University of Kansas
    Format
    297 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Medicinal Chemistry
    Rights
    Copyright held by the author.
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    Abstract
    Trifluoromethanes play an important role in medicinal chemistry, and methods that enable the rapid synthesis of trifluoromethanes from common functional groups are essential for the synthesis of bioactive compounds. We describe a series of Cu-catalyzed decarboxylative trifluoromethylation reactions that enable the conversion of alcohols to trifluoromethanes. These reactions rely on the efficient generation of nucleophilic “Cu–CF3”, and Chapter 1 provides background on the synthesis, stability, and reactivity of this organometallic species. In addition, we discuss the use of halodifluoroacetates as common, inexpensive, and green precursors to “Cu–CF3”. Cu-catalyzed trifluoromethylation of electrophiles was an appealing, but underdeveloped strategy for accessing fluorinated compounds. Chapter 2 describes our entry into Cu-catalyzed decarboxylative trifluoromethylation of bromodifluoroacetates. We discovered that ligand and catalyst activation played critical roles in the development of an efficient Cu-based catalyst system. Trifluoroethylarenes are commonly found in bioactive compounds, and in Chapter 3, we describe a straightforward Cu-catalyzed strategy to access this motif from benzylic bromodifluoroacetates. A key aspect of this reaction involved the generation of active electrophilic species in situ. In Chapter 4, we describe the ability of ligands to alter the regioselectivity of Cu-catalyzed trifluoromethylation reactions. Propargylic bromodifluoroacetates are converted into a mixture of propargylic trifluoromethanes and trifluoromethylallenes using “Cu–CF3”; however, the use of 1,10-phenanthroline inverts the typical regioselectivity, and provides trifluoromethylallenes in high yield and selectivity. This is the first example of ligands controlling the regioselectivity of Cu-based trifluoromethylation reactions.
    URI
    http://hdl.handle.net/1808/26150
    Collections
    • Medicinal Chemistry Dissertations and Theses [81]
    • Dissertations [4473]

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    785-864-8983
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    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
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    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
     

     

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