Over the last forty years the steady use of radical reactions as the key steps in syntheses has increased. The most commonly used radical reagent is tributyl tinhydride. However such tin based radical reagents are toxic and often contaminate the product as they are difficult to remove. As an alternative to these tin reagents, a novel NaBH4/U.V. system was developed. This system was successfully used to effect the radical reduction of various aromatic halides. In light of these results it was thought that other useful transformations such as C-C bond formation could be achieved. Radical cyclisation onto unsaturated bonds, halogen atom transfers radical cyclisation (HATRC) and 1-5 hydrogen atom translocations were explored. This, 1-5 hydrogen atom translocations, methodology has been successfully applied to the synthesis of the spirocyclic natural products (±) horsfiline and coerulescine. With this success the use of the NaBH4/U.V. system on pyridine substrates was explored. Unfortunately this was not achieved with our current understanding of this reaction. However the use of tributylgernamium hydride, which is considered a ‘green’ radical reagent when compared to tin based reagents, proved successful. The novel application of this reagent in the 1-5 hydrogen atom transfer reaction on pyridine substrates was successfully demonstrated. Its use was successfully employed in the synthesis of a pyridine based bioisostere derivative of horsfiline.

In the onset of many chronic illnesses including Parkinson’s, Alzheimer’s, and cardiovascular diseases, there is evidence to support the delicate balance between prooxidant and antioxidant species is shifted in favor of the former. Under these conditions, many reactive oxygen species (ROS) including hydroxyl radicals, are generated. Hydroxyl radicals formed in close proximity to DNA, nucleotides, proteins, and lipids rapidly oxidize these biological molecules in a nonspecific way. However, their toxicity is limited by their short lifetimes. Currently, the mechanism by which hydroxyl radicals are involved in the onset of many illnesses, particularly with regard to lipid peroxidation, has yielded some controversy in the literature. Conventional studies which generate hydroxyl radicals with Fenton chemistry through bolus additions of iron and hydrogen peroxide do not mimic conditions found physiologically because there is a steady-state concentration of hydrogen peroxide concentration found in normal cellular systems. Also, former reports that used fluorescent fatty acids or free probes intercalated within liposomal membranes did not have the probes covalently attached to the phospholipids making up the liposomes. Thus, the actual placement of the probes over the analysis time may vary with experimental conditions. The objective of this research project was to prepare, characterize, and employ liposomes as models for cell membranes during free radical oxidation. Also, compared to the popularly-used technique of electron spin resonance, (ESR), our aim was to use a fluorescence-based approach which yielded the advantages of high sensitivity, fast analysis time, and less expensive equipment requirements. Degradation of fluorescently-tagged liposomes with probes covalently bound to the phospholipids was correlated with the ability of hydroxyl radicals and other possible reactive oxygen species to penetrate into the liposomes to deeper into the lipophilic layer. However, alone this experimental setup may not fully define the mechanistic role of hydroxyl radicals in lipid oxidation. Thus, a complementary approach embracing the use of MALDI-TOF mass spectrometry, lipophilic scavenger studies, and the effects of cholesterol and temperature allow a deeper understanding of the radically-driven oxidation of lipids. It was determined that hydroxyl radicals were generated and reacted with three fluorescent probes.

An experimental approach was taken in determining the quantum yield of Ruthenium(II) with Oxygen using two different Ru complexes. This reaction results in Ruthenium(III) and O2-. The Coulombic interactions caused by a carboxylate functional was found to increase the yield of charge separation. This was done using a diode to measure the intensity of the completed reaction over a certain time frame. The intensities were turned into concentrations. The concentration over time was used to determine the quantum yield. This information is useful in creating more efficient light emitting diodes.

Thesis (Ph. D.)--University of Wyoming, 2006. / Title from PDF title page (viewed on Dec. 20, 2007). Includes bibliographical references.

The 4-substituted glutarimide required for the synthesis of sesbanimide (53) was obtained by free radical addition of iodoacetamide onto the $ alpha, beta$-unsaturated ester (81) mediated by tributyltin; the lactol ring C was prepared by the analogous free radical cyclization of the $ alpha$-bromo-dipropargyl ketal 73. / The syntheses of tricyclic carbapenems involved appropriately substituted monocyclic azetidinone precursors. Free radical 5- exo cyclizations led to the relatively unstable benzo carbapenems 116, 119 and 120. The 6- exo mode, however, afforded stable benzo carbacephems 125, 127, 132 and 133. / $ alpha$-Bromo- and $ alpha{,} alpha$-dibromoazetidinones were converted stereoselectively to the $ alpha$-alkylazetidinones 149 and 153, or to $ beta$-alkylazetidinones 151, 154 and 159 by a free radical addition onto olefins 148 or allyltributyltin.

Radical translocation chemistry has classically been employed for the generation of carboncentred radicals as a means of remotely functionalising nominally unreactive sites. Previous work within the group had investigated vinyl radicals to effect translocation and had identified a need for a more reactive abstracting radical. In this regard, the high energy of alkoxyl radicals would facilitate rapid 1,5-hydrogen abstraction as opposed to simple reduction. This thesis describes the use of alkoxyl radicals, generated from N-alkoxyphthalimides, to abstract a hydrogen atom selectively from the α-position of a lactam ring. Alkoxyl radicals generated from precursors designed to lead to intramolecular trapping of the translocated radical were prone to β-scission in preference to 1,5-hydrogen atom abstraction. This is attributed to a combination of developing π-overlap in the transition state and stabilisation of the resulting radical both by nitrogen and the attached alkyl substituents. Incorporation of an alkenyl trap onto the lactam ring led to successful 1,5-hydrogen atom abstraction and stereoselective cyclisation, although β-scission remained the dominant pathway. Translocation initiated by nitrogen-centred radicals was investigated and it was found that 1,5-hydrogen abstraction occurred in preference to β-scission; intramolecular trapping of the translocated radical proved impossible either because the precursors were unstable to the reaction conditions or because increased steric bulk impeded hydrogen abstraction by the less reactive aminyl radical. Preparation of bicyclic pyrrolidinones via successive 5-endo-5-exo-trig cyclisations was investigated; the precursors were found to undergo direct reduction in preference to cyclisation. Alkyl or aryl groups attached to the a-acylamino carbon may lead to preferential 5-endo cyclisation by stabilisation of the developing radical in the transition state.

This thesis describes efforts to develop new methods for the synthesis of bridged azacycles using nitrogen-directed free radical rearrangements. Free radical addition to 7-azanorbornadienes were carried out to give 7-substituted 2- azanorbornenes (Scheme a.l, X-Y = RS-H or PhSe-H). [illustration in text ...] Scheme a. 1 Nitrogen-directed homoallylic radical rearrangement via intermolecular radical addition. A conceptually novel and theoretically interesting nitrogen-directed neophyl rearrangement (Scheme a.2) was developed into a synthesis of 2- azabenzonorbornanes 2. [illustration in text ...] Scheme a.2 Nitrogen-directed neophyl-like rearrangement to 2-azabenzonorbornanes. In this case the radical 1 was generated by Barton deoxygenation of 7- azabenzonorbornanols. The effect on rearrangement of bicyclic core substitution and of aromatic ring electronics was probed in some detail, and the process was synthetically useful for a wide range of substrates. Variation of the protecting group on nitrogen was investigated and the product profiles from neophyl-like rearrangement were consistent with a process driven by the stability of a radical α to nitrogen as a result of SOMO-lone pair orbital interaction. The kinetics and mechanism of these processes are examined where appropriate, leading to estimates of rate constants for the rearrangements.

Thesis (Ph.D.) -- McMaster University, 2001. / Includes bibliographical references. Also available via World Wide Web.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1951. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves [80]-82).

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Document formatted into pages; contains xxiii, 454 p.; also includes graphics (some col.). Includes bibliographical references (p. 246-259). Available online via OhioLINK's ETD Center