New Complexity-Building Reactions of α-Keto Esters

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  • March 21, 2019
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  • Lee, Samuel
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • I. Introduction: Importance of Asymmetric Catalysis and the Reactivity Patterns of α-Keto Esters II. Synthesis of Complex Tertiary Glycolates by Enantioconvergent Arylation of Stereochemically Labile α-Keto Esters Enantioconvergent arylation reactions of boronic acids and racemic β-stereogenic α-keto esters have been developed. The reactions are catalyzed by a chiral (diene)Rh(I) complex and provide a wide array of β-stereogenic tertiary aryl glycolate derivatives with high levels of diastereo- and enantioselectivity. Racemization studies employing a series of sterically differentiated tertiary amines suggest that the steric nature of the amine base additive exerts a significant influence on the rate of substrate racemization. III. Palladium-Catalyzed β-Arylation of α-Keto Esters A catalyst system derived from commercially available Pd2(dba)3 and PtBu3 has been applied to the coupling of α-keto ester enolates and aryl bromides. The reaction provides access to an array of β-stereogenic α-keto ester derivatives. When the air stable ligand precursor PtBu3·HBF4 is employed, the reaction can be carried out without use of a glovebox. The derived products are of broad interest given the prevalence of the α-keto acid substructure in biologically important molecules. IV. Catalytic Enantioselective [3+2] Cycloaddition of α-Keto Ester Enolates and Nitrile Oxides An enantioselective [3+2] cycloaddition reaction between nitrile oxides and transiently generated enolates of α-keto esters has been developed. The catalyst system was found to be compatible with in situ nitrile oxide generation conditions. A versatile array of nitrile oxides and α-keto esters could participate in the cycloaddition, providing novel 5-hydroxy-2-isoxazolines in high chemical yield with high levels of diastereo- and enantioselectivity. Notably, the optimal reaction conditions circumvented concurrent reaction via O-imidoylation and hetero-[3+2] pathways.
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  • In Copyright
Advisor
  • Nicewicz, David
  • Johnson, Jeffrey
  • Brustad, Eric
  • Miller, Alexander
  • Meek, Simon
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill
Graduation year
  • 2017
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