Graduation Semester and Year
Fall 2025
Language
English
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Chemistry
Department
Chemistry and Biochemistry
First Advisor
Carl J. Lovely
Second Advisor
Junha Jeon
Third Advisor
Joseph A. Buonomo
Fourth Advisor
Kayunta Johnson-Winters
Abstract
The work described in this dissertation focuses on the study of oxidative dearomatization reactions of tri-substituted N-methoxy ureas along with further functionalization of the dearomatized framework. These studies enable the synthesis of molecules related to the core framework of KB343 using oxidative dearomatization as a key step. The second part of this dissertation focuses on study of fluoride catalyzed hydroamination reactions along with synthesis of metabolites of daidzein to investigate its chiral and achiral separation.
Chapter 1 is an overview of the importance of dearomatization reaction as a tool to synthesize natural products. It describes recent examples from the literature published during last three years where total synthesis of natural products have used dearomatization as a key step.
In Chapter 2, synthetic studies of dearomatization of N-methoxy ureas using hypervalent iodine reagents to form spiroimidazolidinone frameworks are described along with its scope and limitations. Initial attempts to investigate the dearomatization of disubstituted N-methoxy ureas resulted in the formation of urethane derivatives by net nucleophilic attack of the reaction solvent hexafluoroisopropanol. However, attempts to dearomatize tri-substituted N-methoxy ureas yielded the desired spirocyclic product via a putative nitrenium ion formation in moderate to excellent yield. Also, scouting reactions involving the elaboration of the dearomatized framework are reported.
Chapter 3 describes the synthetic studies towards the core framework of the KB343 using oxidative dearomatization as a key step. Various approaches toward the suitably protected trisubstituted N-methoxy ureas related to the core framework have been established using commercially available 4-hydroxyphenylglycine as a starting point. Upon successful construction of the targeted trisubstituted urea via seven step synthesis, oxidative dearomatization gave the desired spirocyclic product. Elaboration of the adduct by a [3,3]-sigmatropic rearrangement (cyanate to isocyanate) resulted in the successful installation of cyclic guanidine on one of the double bonds of the dearomatized product after trapping the other double bond by synthesis of furan derivative. Attempts toward the construction of the decalin ring via Grignard reaction are ongoing.
In Chapter 4, a study of the fluoride-catalyzed hydroamination reactions of propargylic urethanes to synthesize oxazolidinones is discussed. The work documents both the optimization of the reactions as well as study of substrate scope highlighting its broad applications.
The final chapter outcomes a collaborative study of some metabolites of daidzein. The synthesis of several metabolites are described. In addition, the chiral and achiral separation of the isomers along with determination of absolute configuration of all the stereoisomers of the metabolites are reported.
Keywords
Chemistry, Organic, Synthetic, Dearomatization, KB343, Natural products, Heterocyclic chemistry, Marine natural products, Hydroamination, Total synthesis
Disciplines
Organic Chemistry
License
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Recommended Citation
Parveen, Nazmee, "Dearomatization reactions of N-methoxy ureas for application toward a total synthesis of KB343 and investigation of fluoride-catalyzed hydroamination reactions" (2025). Chemistry & Biochemistry Dissertations. 293.
https://mavmatrix.uta.edu/chemistry_dissertations/293