The goal of this project was to synthesize a fluorinated disaccharide as a substrate or inhibitor for a glycosidase enzyme. A substrate analogue with only one strategically positioned fluorine atom could be used to probe such a complex interaction by using ¹⁹F NMR to monitor any changes in chemical shift, line width, and p coupling constants which arise when the analogue binds to the enzyme. Such changes would be more easily observed by using ¹⁹F NMR to monitor the perturbations around the single F nucleus than by monitoring the ¹H NMR because the spectrum in the latter case is much more complex due to the number of protons inherent in both the natural substrate and the enzyme. The compounds 3,4,6-tri-0-acetyl-2-deoxy-2-fluoro-α-D-glucopyranosyl bromide [5] and 2,3-di-0-acetyl-l,6-anhydro-β-D-glucose [2] were synthesized as appropriate starting materials and then coupled in diethyl ether in the presence of Ag₂CO₃, using AgSO₃CF₃ as a catalyst; these are the simple conditions of the well-known Koenigs-Knorr reaction. The coupling of a halosugar bearing a non-participating group at C-2 with an alcohol in low concentration has been shown by many other workers to result in a mixture of a- and 3-linked products, with the former being predominant. In this study, only the a-linked disaccharide 2,3-di-0-acetyl-l,6-anhydro-4-0-(3,4,6-tri-0-acetyl-2-deoxy-2-fluoro-α-D-glycopyranosyl)-B-D-glucopyranose [12] was obtained, the corresponding β-linked disaccharide was not observed in the reaction mixture. This fact suggests that some factor in either the reaction conditions employed or in the nature of the two sugars involved in the coupling was responsible for the exclusive production of only one type of linkage. The α-linked disaccharide [12] was deprotected to give the free sugar 2'-deoxy-2'-fluoro-maltose (4-0-(2-deoxy-2-fluoro-α-D-glucopyranosyl)-D-glucopyranose [14]) which is the C-2' fluorinated analogue of maltose. This compound should be a suitable probe for enzyme systems such as Maltase or α-glycosidase. The proton decoupled ¹⁹F NMR of [14] displayed two distinct resonances separated by 0.1 ppm which could be due to the α and β anomeric forms of that compound. The optical rotations values and the α/β anomeric ratios deduced from the ¹H NMR spectra for maltose and [14] were comparable, suggesting that this may indeed be the case. The synthesis of 4-0-(2-deoxy-2-fluoro-α-D-galacto-pyranosyl)-D-glucopyranose [17] was initiated with the view of using such a compound to study an α-galactosidase system; the partial synthesis of this molecule is also included herein. The conformational aspects of all the sugars synthesized in this work were deduced from ¹H NMR and then confirmed by ¹⁹F NMR and optical rotation. The ¹⁹F NMR spectra of the disaccharides were simple and were shown to provide sufficient information for the deduction of the conformational and configurational aspects of these sugars in the region of interest. This indicated that changes in the region about the fluorine could be monitored using ¹⁹F NMR and that these sugars could thus prove to be valuable probes for the elucidation of enzyme mechanisms. / Science, Faculty of / Chemistry, Department of / Graduate

Addition reactions of perf1uorothio1acetic acid (TFTAA) with organic and inorganic substrates were studied and six new compounds containing the trif1uoroacety1 group have been prepared. Two types of reactions were observed, free radical and nucleophilic addition. Under the influence of ultraviolet light, TFTAA (CF₃COSH) adds to olefins to form 1:1 adducts. The CF₃COS• radical appears to be the adding species. Three new olefin adducts were prepared: CF₃COSCFHCF₂H, CF₃COSCH₂CF₂H, and CF₃COSCH₂CFH₂. In addition, this was found to be a new way to prepare CF₃COSCH₂CH₃, which had been previously prepared by another route¹. Physical constants, analytical data, infrared, ultraviolet, nmr and mass spectra are presented supporting the proposed structures for these compounds. Nucleophilic addition adducts were formed with TFTAA and some organic and inorganic materials. TFTAA is a strong acid and the CF₃ COS⁻ ion was found to act as a nucleophile with several substrates. With hexafluoroacetone, addition of TFTAA across the carbonyl gave CF₃COSC(CF₃)₂OH. This structure is supported by analytical data, gas chromatographic data, infrared, ultraviolet, nmr, and mass spectra. Ethylene oxide and TFTAA react to produce the alcohol addition product, CF₃COSCH₂CH₂0H, which is supported by analytical data, nmr infrared, and mass spectra. Sulfur trioxide was studied as a representative inorganic molecule. TFTAA adds to this Lewis acid to form the sulfonate, (CF₃COS)₂S0₂. Analytical data, infrared, ultraviolet, nmr and mass spectra are reported here. All of the reactions, except the free radical reactions, occurred spontaneously and exothermically upon mixing the two reactants. A new method of preparing CF₃COSH, by reacting KSH with (CF₃CO)₂O, is also presented ¹M. Hauptschein, C.S. Stokes, and E.A. Nodiff, J. Am. Chem. Soc. 74, 4005 (1952)

Organofluorine compounds are highly desirable products owing to the unique physical and chemical properties imparted by fluorine. Fluorocarbons are useful molecules that are used in multiple industries such as refrigeration, agrochemicals, pharmaceuticals, insecticides, high-value fluoropolymers and reagents in catalysis. As ligands, they are privileged in the relative inertness of the C–F bonds and their electrophilicity, which makes them ideal candidates for coordination chemistry with late, electron rich metals. Chapter 2 describes the preparation of new Ni metallacyclopentene complexes with phosphite and bis(phosphine) ligands and investigates the reaction of the latter with Lewis acidic trimethylsilyltriflate, TMSOTf (Tf = SO2CF3). As phosphine ligands react with the perfluoro-butadiene (PFB) substrate, the phosphite complex Ni((2-C4F6)[P(O-i-Pr)3]2 (2-1) was prepared from Ni(cod)2 /2 P(O-i-Pr)3 and excess PFB. Reaction of 2.1 with bis(phosphine) dppe [1,2-bis(diphenylphosphine)ethane] proceeded slowly with release of P(O-i-Pr)3 and formation of electron-rich Ni(2-C4F6)(dppe) (2-2) that undergoes fluoride abstraction using TMSOTf. The major product is proposed to be a dienyl complex resulting from ring contraction and cycloreversion. In Chapter 3 we investigate reactions of fluoroalkenes with cobalt hydrides containing phosphine and phosphite ligands in order to see if their reactivity can be controlled by the ligands’ steric and electronic properties. The four cobalt compounds used were CoH[P(OiPr)3]4 (3-1), CoH[P(O-o-tol)3]n (3-2), CoH(triphos)(CO) (3-3); [triphos = bis(diphenylphosphinoethyl)-phenylphosphine], and CoH(PPh3)3(N2) (3-4). In light of previous reports of tetrafluoroethylene insertion into Co carbonyl hydrides, we were surprised that analogous reactivity was not observed except for 3-4. Instead, reactions with hexafluoropropene gave a mixture of alkene cobalt fluoride and cobalt alkenyl complexes. In Chapter 4 we summarize our contributions to knowledge and compare our results to those from the current state of the art.

No description available.

The following work describes the synthesis of compounds carrying a vicinal difluoro motif and the evaluation of this structural element to influence the conformation of organic molecules. The synthesis of erythro and threo 1,2-difluoro-1,2-diphenylethane was achieved by bromofluorination and subsequent halogen exchange from stilbene. Oxidative degradation of the phenyl rings allowed to access erythro and threo 2,3- difluorosuccinic acids and a variety of derivatives thereof. The conformations of these compounds were investigated by means of X-ray analysis and NMR spectroscopy. Conformational analysis of derivatives of 2,3-difluorosuccinic acid was carried out using JHFandJHHNMR coupling constants. A clear preference for the conformations in which the two vicinal C-F bonds are gauche emerged from these calculations, which was confirmed by temperature and solvent dependent NMR analyses. The vicinal difluoro motif was incorporated into small peptide structures. In the solid state, a strong preference to align the vicinal C-F bonds gauche to each other was observed and when adjacent to an amide moiety, the C-F bond was found to prefer an anti periplanar orientation with respect to the carbonyl bond. These effects appeared to override steric and electrostatic interactions. The conformation of these fluorinecontaining peptides showed a clear dependence on the stereochemicaol rientation of the C-F bonds, and this appears to be an effective tool for influencing the secondary and consequently tertiary structure in a predictable manner. In order to access single enantiomerso f peptides having the vicinal difluoro, motif, a stereoselectiver oute to R,R and SS 2,3-difluorosuccinic was developed. This involved nucleophilic fluorination of the cyclic sulfates generated from (R, R)- and (SS)- diethyl tartrates and subsequent deoxofluorination of the intermediate fluorohydrins.

Thesis (M.S.)--Oregon State University, 2008. / Printout. Includes bibliographical references (leaves 56-58). Also available on the World Wide Web.

Thesis (Ph. D.)--Rutgers University, 2010. / "Graduate Program in Chemistry." Includes bibliographical references.

Thesis (Ph.D.) - University of St Andrews, May 2009.

published_or_final_version / Chemistry / Master / Master of Science

No description available.