Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.791720
Title: Novel fluorination methodology through computational insight : tuning fluoride through hydrogen bonding
Author: Ascough, David
ISNI:       0000 0004 8503 2844
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2019
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Abstract:
Even though carbon-fluorine bonds are uncommon in nature, fluorination of organic molecules is well-known to induce desirable biological properties. Methods for fluorination are therefore highly sought after; however, one of the most convenient sources of fluorine, inorganic fluoride salts, are inconvenient reagents. Inspired by the fluorinase enzyme's binding of fluoride through hydrogen bonding, this work describes the computational investigation of the effects of hydrogen bonding on fluoride reactivity and selectivity, in collaboration with experimental chemistry, to develop novel catalytic methods for asymmetric fluorination of organic molecules with simple fluoride reagents. Chapter 1 summarizes the current state of the art for using fluoride as a reagent for fluorination of organic molecules. Computational methods and challenges in modeling such systems are also described. Chapter 2 describes the study and rationalization of experimental data on the effect of hydrogen bond donor strength on the reactivity and selectivity of urea-fluoride complexes as reagents in a model SN2 vs E2 reaction with primary bromide substrate. This chapter also describes benchmarking of computational methods for accurate description of fluoride. Chapter 3 describes the development of hydrogen bonding phase-transfer catalysis (HB PTC) and its application to asymmetric fluorination with group 1 metal fluoride salts and chiral urea organocatalyst, including mechanistic study and computationally guided catalyst design. Chapter 4 describes the application of HB PTC to asymmetric desymmetrization of aziridinium ions. Computation yields insight into the origins of enantioselectivity and the activation of potassium fluoride as fluoride source. The final chapter discusses the computational insight into the effects of hydrogen bonding on fluoride, including consequences for enantioselectivity and catalytic kinetics.
Supervisor: Gouverneur, Veronique ; Paton, Robert Sponsor: Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.791720  DOI: Not available
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