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Radical Fragmentations

Title: Radical Fragmentations: From Conformational Control of Enediyne Reactivity to 1,2-C,O Transposition and Metal-Free Synthesis of Benzoates and Benzamides from Phenols.
Name(s): Baroudi, Abdulkader, author
Alabugin, Igor V., professor directing dissertation
Locke, Bruce R., university representative
Dudley, Gregory B., committee member
Steinbock, Oliver, committee member
Department of Chemistry and Biochemistry, degree granting department
Florida State University, degree granting institution
Type of Resource: text
Genre: Text
Issuance: monographic
Date Issued: 2010
Publisher: Florida State University
Place of Publication: Tallahassee, Florida
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The work described in this thesis is a demonstration of how theory and experiment can be used side by side in developing research in organic chemistry, from mechanistic studies to the design of new reactions. In chapter one we describe a variety of fragmentations and rearrangements following Bergman cyclization in enediynes equipped with acetal rings mimicking the carbohydrate moiety of natural enediyne antibiotics of the esperamicine and calchiamicine families. In the first step of all these processes, intramolecular H-atom abstraction efficiently intercepts the p-benzyne product of the Bergman cyclization through a six-membered transition state (TS) and transforms the p-benzyne into a new more stable radical. Depending on the substitution pattern and reaction conditions, this radical follows four alternative paths: (a) abstraction of an external hydrogen atom, (b) O-neophyl rearrangement which transposes O- and C-atoms of the substituent, (c) fragmentation of the O─C bond in the acetal ring, or (d) fragmentation with elimination of the appended acetal moiety as a whole. Experiments with varying concentrations of external H-atom donor (1,4-cyclohexadiene) were performed in order to gain further insight into the competition between intermolecular H-abstraction and the fragmentations. The Thorpe-Ingold effect in gem-dimethyl substituted enediynes enhances the efficiency of fragmentation to the extent where it cannot be prevented even by a large excess of external H-atom donor. These processes provide insight into a possible mechanism of unusual fragmentation of esperamicin A1 upon its Bergman cycloaromatization and lay foundation for a new approach for the conformational control of reactivity of these natural antitumor antibiotics. Such an approach, in conjunction with supramolecular constraints, may provide a plausible mechanism for resistance to enediyne antibiotics by the enediyne-producing microorganisms. In chapter two we demonstrate our new reaction that can transform phenol derivatives directly into esters and amides of benzoic acids via a new radical cascade. This newly designed radical transformation was inspired by the radical rearrangement discovered for one of the THP-equipped enediynes described in chapter one. We found that this process can be rendered practically useful for C,O-transposition in diaryl thiocarbonates and thiocarbamates. These compounds are available in a single high-yielding step from phenols, and can be transformed into benzoates derivatives through a radical cascade inspired by selective addition of silyl radicals at the sulfur atom of the C=S moiety. This addition step, analogous to the first step of the Barton-McCombie reaction, affords an anomerically stabilized carbon radical which can undergo a reversible 1,2 O→C transposition through O-neophyl rearrangement. The usually unfavorable equilibrium in the rearrangement step is shifted via a highly exothermic C─S bond scission in the O-centered radical which furnishes the final benzoic ester or benzamide product. This sequence provides a metal-free approach for the preparation of benzoate derivatives from phenols, a potentially useful alternative to metal catalyzed carbonylation of aryl triflates.
Identifier: FSU_migr_etd-4623 (IID)
Submitted Note: A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy.
Degree Awarded: Fall Semester, 2010.
Date of Defense: October 13, 2010.
Keywords: Enediyne, Radical, Ester, Neophyl Rearrangement, Amide, Esperamicin, Phenol, Fragmentation
Bibliography Note: Includes bibliographical references.
Advisory Committee: Igor V. Alabugin, Professor Directing Dissertation; Bruce R. Locke, University Representative; Gregory B. Dudley, Committee Member; Oliver Steinbock, Committee Member.
Subject(s): Biochemistry
Molecular biology
Persistent Link to This Record:
Owner Institution: FSU

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Baroudi, A. (2010). Radical Fragmentations: From Conformational Control of Enediyne Reactivity to 1,2-C,O Transposition and Metal-Free Synthesis of Benzoates and Benzamides from Phenols. Retrieved from