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Date of Award
2015
Publisher
North Dakota State University
Document Type
Dissertation
Degree Awarded
Doctor of Philosophy (PhD)
Department
Chemistry and Biochemistry
College
Science and Mathematics
Faculty Advisor
Sibi, Mukund P.
Description
Development of novel asymmetric and catalytic methods for synthesizing small organic molecules containing hindered quaternary and tertiary centers is a major challenge and a dynamic area of investigation in synthetic organic chemistry. The incorporation of these chiral centers into small molecules such as cyclopropanes, aziridines or isoxazolidines is important because they are present in a large number of biologically active natural products as well as in synthetically designed pharmaceutical agents. However, the synthesis of non-natural compounds containing quaternary and tertiary centers that have potential as therapeutics are scarce due to the limited number of readily available methods. We have successfully used 1-(benzyloxy)imidazole as a new bidentate coordinating template for dipolar cycloaddition and cyclization reactions using chiral Lewis acid as a promoter to access these highly functionalized small molecules in high yields and selectivity. Chapter 1. Review for Michael Initiated Ring Closure (MIRC) reaction. The chapter provides different diastereo- and enantioselective strategies for the construction of chiral cyclopropanes. Also, the chapter will provide the current methodologies developed for MIRC reaction. Chapter 2. Development of a novel chiral Lewis acid methodology for synthesizing highly strained cyclopropanes with chiral quaternary and tertiary centers using Michael Initiated Ring Closure (MIRC) reaction for β-substituted and β,β-disubstituted enones with N-benzyloxy imidazole as an achiral template. Different types of nucleophiles such as sulfur ylides and bromomalonate were successfully employed in the MIRC reaction. Chapter 3. Development of a novel chiral Lewis acid methodology for synthesizing highly strained chiral CF3-substituted aziridines using aza-Michael initiated ring closure reaction (aza-MIRC). The reaction involves β,β-disubstituted enones with N-benzyloxy imidazole as an achiral template and N-nosyloxy carbamate as ‘nitrene’ source. Chapter 4. Development of N-benzyloxy imidazole template as a chelating scaffold for chiral Lewis acid catalyzed enantioselective nitrone cycloaddition of β,β-disubstituted enones for the construction of isoxazolidines with trifluoromethyl group is described. The N-benzyloxy imidazole in the cycloadduct was efficiently transformed into corresponding isoxazolidine ester, which could be further converted into useful precursors such as β-hydroxycarbonyls, 1,3-diols, β-aminoalcohols, β-aminoacids, β-lactams and other functionalized building blocks.
Recommended Citation
Moorthy, Ramkumar, "Novel Asymmetric Approaches for Construction of Small Molecules by Cyclization and Cycloaddition" (2015). Chemistry and Biochemistry. 39.
https://digitalcommons.ndsu.edu/chem-biochem/39
Rights
NDSU Policy 190.6.2
Rights Link
https://www.ndsu.edu/fileadmin/policy/190.pdf
Handle Identifier
http://hdl.handle.net/10365/25538