ABSTRACT OF THE DISSERTATION
Studies of Halogenated Lipids and
Progress Toward the Synthesis of Crotogoudin
Dmitriy Igorovich Uchenik
Doctor of Philosophy in Chemistry
University of California, Irvine, 2017
Professor Christopher D. Vanderwal, Chair
This dissertation describes three separate projects which range from work toward the
development of new chemical methods to the synthesis of natural products. Chapter one
introduces the intricacies involved in bimolecular elimination reactions and reports my
efforts to elucidate the source of the highly diastereoselective dehydrohalogenation of
b-dichloro sulfates. Our group has previously found that exposure of b,b,-dichloro
sulfates to LDA provided exclusively the (E)-vinyl sulfate while the same elimination
conducted with t-BuOK gave a 1:5 ratio of (E)- to (Z)- alkene diastereomers. Experiments
exploring the effects of base strength, different countercations, and substrate substitution
were carried out to attempt to elucidate the source of this surprising diastereocontrol.
Early elimination experiments performed on 2,2-dichlorohexyl sulfate supported an
initial hypothesis of diastereocontrol based on competing cation chelation, but further
experimentation demonstrated that the trend did not extend to other b-chloro sulfates.
Chapter two describes synthetic explorations toward the synthesis of the sponge derived
natural product mollenyne A. Synthetic efforts focused on the synthesis of the
dibromochlorohydrin stereo-triad demonstrated the challenge associated with the
regioselective synthesis of a trisubstituted (E)-alkenyl bromide. Failing to install the alkenyl bromide via hydrometalation, a ring-closing metathesis strategy was proposed to
set the alkene geometry. While a 1,1-disubstituted alkenyl bromide was synthesized, we
were unable to achieve the desired metathesis.
Chapter 3 focuses on my efforts toward the total synthesis of the seco-atisane diterpene
crotogoudin. A variety of methods for the installation of bicyclo-[2.2.2]-octanes are
discussed in the context of various natural product syntheses and the two previous
syntheses of crotogoudin by the Carreira and Liu groups are presented. Work toward
improving the synthetic approach designed by Dr. Peter Mai led to the discovery of an
unprecedented, oxygen-dependent copper catalyzed conjugate reduction. An expansion
of Snyder’s manganese(III) mediated free radical enolate cyclization is presented as a
novel method for forming bicyclo-[2.2.2]-octanes.