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Development of Crown Ether Nucleophilic Catalysts (CENCs) and their Application in Rapid Fluorination of Silicon for PET Imaging & Diversification Reactions of γ-Silyl Allenyl Esters to All-carbon Quaternary Stereogenic Centers

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Date Issued:
2018
Abstract/Description:
In this dissertation, we discuss the development of new phase transfer agents, which are capable of rapid fluorination of silicon. These are 18-C-6 derivatives containing a hydroxyl group in the side arm (podand), also known as C-pivot lariats. The syntheses of these lariats including several that have not been previously reported and their efficient purification are described. The synthesis route leads to a robust and generalized approach to obtain these lariats on the gram scale. These agents were initially designed for applications in positron emission tomography (PET). In this medical imaging modality, tracer agents containing silicon have found promising utility as fluoride receptors for more rapid radiolabeling. Phase transfer agents are generally required for 18F-labeling due to the low solubility in organic reaction media and reactivity of cyclotron-generated [18F]potassium fluoride. We envisioned that 18-C-6 derivatives may serve as both phase transfer agents as well as nucleophilic catalysts (CENCs). In this conception, CENCs were rapidly pre-complexed with KF followed by silicon fluorination, which takes advantage of a previously established silicon dianion mechanism. In collaboration with researchers at the NIH, we studied the effect of various linkers connecting the metal chelating unit to the nucleophilic hydroxyl group on the radiofluorination of silicon under mild condition. A hydrolysis resistant aryl silicon fragment has also been developed that contains various functional groups for convenient attachment to the potential PET radiotracer agents. In a second project, we demonstrate the unique reactivity of γ-silyl allenyl esters. Taking advantage of the silyl group as a fluoride acceptor, these allenoates readily underwent addition to a variety of carbon electrophiles, including aryl fluorides, to afford all-carbon quaternary centers bearing an ethynyl group. Surprisingly, in the presence of aldehydes, exclusive bis-substitution occurs at the γ-position to afford the dicarbinol. Details relating to reaction optimization and substrate scope for both the reactions are presented. Dicarbinol allenes were subsequently converted to highly substituted δ-lactones, a novel 6-hydro-2-pyrone as single diastereomers.
Title: Development of Crown Ether Nucleophilic Catalysts (CENCs) and their Application in Rapid Fluorination of Silicon for PET Imaging & Diversification Reactions of γ-Silyl Allenyl Esters to All-carbon Quaternary Stereogenic Centers.
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Name(s): Jana, Susovan, author
Lepore, Salvatore D., Thesis advisor
Florida Atlantic University, Degree grantor
Charles E. Schmidt College of Science
Department of Chemistry and Biochemistry
Type of Resource: text
Genre: Electronic Thesis Or Dissertation
Date Created: 2018
Date Issued: 2018
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 258 p.
Language(s): English
Abstract/Description: In this dissertation, we discuss the development of new phase transfer agents, which are capable of rapid fluorination of silicon. These are 18-C-6 derivatives containing a hydroxyl group in the side arm (podand), also known as C-pivot lariats. The syntheses of these lariats including several that have not been previously reported and their efficient purification are described. The synthesis route leads to a robust and generalized approach to obtain these lariats on the gram scale. These agents were initially designed for applications in positron emission tomography (PET). In this medical imaging modality, tracer agents containing silicon have found promising utility as fluoride receptors for more rapid radiolabeling. Phase transfer agents are generally required for 18F-labeling due to the low solubility in organic reaction media and reactivity of cyclotron-generated [18F]potassium fluoride. We envisioned that 18-C-6 derivatives may serve as both phase transfer agents as well as nucleophilic catalysts (CENCs). In this conception, CENCs were rapidly pre-complexed with KF followed by silicon fluorination, which takes advantage of a previously established silicon dianion mechanism. In collaboration with researchers at the NIH, we studied the effect of various linkers connecting the metal chelating unit to the nucleophilic hydroxyl group on the radiofluorination of silicon under mild condition. A hydrolysis resistant aryl silicon fragment has also been developed that contains various functional groups for convenient attachment to the potential PET radiotracer agents. In a second project, we demonstrate the unique reactivity of γ-silyl allenyl esters. Taking advantage of the silyl group as a fluoride acceptor, these allenoates readily underwent addition to a variety of carbon electrophiles, including aryl fluorides, to afford all-carbon quaternary centers bearing an ethynyl group. Surprisingly, in the presence of aldehydes, exclusive bis-substitution occurs at the γ-position to afford the dicarbinol. Details relating to reaction optimization and substrate scope for both the reactions are presented. Dicarbinol allenes were subsequently converted to highly substituted δ-lactones, a novel 6-hydro-2-pyrone as single diastereomers.
Identifier: FA00013073 (IID)
Degree granted: Dissertation (Ph.D.)--Florida Atlantic University, 2018.
Collection: FAU Electronic Theses and Dissertations Collection
Note(s): Includes bibliography.
Subject(s): Phase-transfer catalysis.
Silicon.
Positron-Emission Tomography.
Crown ethers.
Radioactive tracers.
Fluorination.
Held by: Florida Atlantic University Libraries
Sublocation: Digital Library
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FA00013073
Use and Reproduction: Copyright © is held by the author, with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
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Owner Institution: FAU
Is Part of Series: Florida Atlantic University Digital Library Collections.