| dc.description.abstract | 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. | en_US |
