UC Irvine

ABSTRACT OF THE DISSERTATION

Studies of Halogenated Lipids and

Progress Toward the Synthesis of Crotogoudin

By

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.