I. Mechanistic studies of a copper-catalyzed electrophilic amination of diorganozinc reagents reagents by O-benzoyl N,N-dialkylhydroxylamines II. Development of a 3-Exo-Dig cyclization for the preparation of vinylidene cyclopropanes III. Total synthesis of (+)-polyanthellin A

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  • Mechanistic studies of a copper-catalyzed electrophilic amination of diorganozinc reagents reagents by O-benzoyl N,N-dialkylhydroxylamines
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  • March 21, 2019
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  • Campbell, Matthew James
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • I. Mechanistic Studies of a Copper-Catalyzed Electrophilic Amination of Diorganozinc Reagents by O-Benzoyl N,N-Dialkylhydroxylamines The mechanism of the Cu-catalyzed amination of R2Zn reagents by O-benzoyl N,N-dialkylhydroxylamines has been investigated. An SN2 pathway has been supported because: (i) stoichiometrically generated cuprates were used to prove zinc is not essential in the C-N bond forming step; (ii) the configuration at the reacting carbon is retained through the reaction, ruling out a radical pathway; (iii) the endocyclic restriction test proceeded without intramolecular amination. A Cu-catalyzed amination of Grignard reagents was realized after experiments determined the relative rates of O-acylation, transmetalation, and C-N bond formation were favorable. O-Mesitoyl N,N-dialkylhydroxylamines were found to be suitable R2N(+) synthons for the uncatalyzed amination of Grignard reagents, including unhindered vinyl Grignard reagents. II. Development of a 3-Exo-Dig Cyclization for the Preparation of Vinylidene Cyclopropanes The first all-carbon 3-exo-dig cyclization was developed. These cyclizations lead to vinylidene cyclopropanes with electron-withdrawing substituents, products that are not available using carbene chemistry. Both cyclic and acyclic precursors can be used with equal efficacy, although high dilution conditions were necessary to enable cyclization of the latter. The products were amenable to a number of common derivatizations, including halogenation, hydrogenation, and hydroboration. III. Total Synthesis of (+)-Polyanthellin A (+)-Polyanthellin A was synthesized in 15 linear steps from methallyl alcohol in 2% overall yield, with an average yield of 77% per step. This synthesis demonstrates the utility of the [3+2]-cycloaddition between cyclopropanes and aldehydes in a complex setting. The use of the hindered catalyst, MADNTf?2?, was essential to ensure a successful cyclization, and has extended the scope of the cycloaddition to include sensitive protected β-hydroxyaldehydes. Other key steps included a Cu-catalyzed cyclopropanation, ring-closing metathesis, selective alkene oxidation, and an iodoetherification.
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  • Johnson, Jeffrey
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  • University of North Carolina at Chapel Hill
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  • October 11, 2010

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