STEREOSELECTIVE FUNCTIONALIZATION OF MELDRUM'S ACIDS AND THE EFFORTS TOWARD TOTAL SYNTHESIS OF ECHINOSPORIN Public Deposited

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  • March 19, 2019
Creator
  • Do, Dung
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • I. Cu(II)-Catalyzed Aerobic Hydroperoxidation of Meldrum's Acid Derivatives and Application in Intramolecular Functionalization to Access Complex Building Blocks Aerobic hydroperoxidation of Meldrum's acid derivatives via a Cu(II)-catalyzed process is presented. The mild reaction conditions are tolerant to variety of vulnerable functional groups. Au(I)-catalyzed endoperoxidations of hydroperoxyalkynes have been reported for the first time. Cleavage of the OO bond provides 1,n-diols with differentiation of the hydroxy groups. A novel research plan centered on the hydroperoxidation of designed Meldrum's acids to generally access fully substituted hemiketal-viable substrates for preparation of complex building blocks is also discussed. II. Conceptual Blueprint for a Stereoselective Heterofunctionalization of Carbonyl Compounds The glamour of a general stereoselective heterofunctionalization of carbonyl compounds encourage us to develop a novel a-heterofunctionalization of lactone. The strategy based on a highly diastereoselective Michael addition of variety of nucleophiles to readily accessible chiral alkylidene Meldrum's acid and a feasible heterofunctionalization of Meldrum's acids to access difunctionalization adducts. Those compounds have been carried on a symmetry-breaking intramolecular lactonization to reveal a new stereocenter with excellent chirality induction at carbon bearing heterofunctional group. Limited efforts provided a proof of concept for a stereoselective fluorination of lactone. III. Efforts Toward The Total Synthesis of Echinosoirin Two approaches for the construction of the echinosporin core are presented. A key strategy includes the rapid formation of the fully substituted-dihydropyran substructure via intermolecular inverse electron demand hetero Diels-Alder reaction of a chiral heterodiene. Highly diastereoselective cyclizations realized by the use of copper(II) triflate and tBu-box ligand, provided access to the dihydropyran core. The stereochemical features of this cycloaddition were previously well established and produced the dihydropyran with high diastereocontrol. An advanced intermediates diazoketone 3.54 was prepared as a single diastereomer in mulltigram-scale and will provide requisite material for further manipulations.
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  • In Copyright
Advisor
  • Johnson, Jeffrey
  • Brookhart, Maurice
  • Templeton, Joseph
  • Alexanian, Erik
  • Nicewicz, David
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2014
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  • Chapel Hill, NC
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