Tesis por compendio / [EN] Cryopreserved boar sperm is not used extensively for artificial insemination due to poor fertility rates of the sperm after freezing and thawing. The sperm membrane is damaged when cooled from body temperature to 5 ºC (cold shock), as well as during the freeze-thaw process. Increasing the cholesterol content of boar sperm membranes could increase their post-thaw survival, similarly to other species that are cold shock sensitive. Cholesterol can be easily added to sperm membranes using cholesterol-loaded cyclodextrins (CLC). Treating sperm from different species susceptible to cold-shock with CLC before cryopreservation improves sperm cryosurvival. Egg yolk and glycerol are common constituents of extenders used for boar sperm cryopreservation. However, conventional freezing extenders could not be the appropriate for CLC-treated sperm. The aim of this Thesis is to evaluate cryosurvival of CLC or cyclodextrin-treated boar sperm in three different conditions: using conventional freezing extenders, using extenders with alternative concentrations of glycerol and egg yolk and using amides as cryoprotectants. CLC or methyl- ß-cyclodextrin treatment (1 mg/120 x 106 sperm) prior to cryopreservation using a conventional freezing extenders provided either slight or no benefit, respectively, to post-thaw sperm plasma membrane integrity (+ 8%; P < 0.05) and motility (P > 0.05). In addition, sperm from both, good and poor freezers, responded similarly to CLC treatment (P > 0.05). Reduction in egg yolk concentration from 20 to 10% was detrimental for post-thaw sperm viability, even in semen treated with CLC (- 12%; P < 0.05). On the other hand, it was observed that traditional concentration of glycerol (3%) was not the appropriate to freeze CLC-treated sperm (- 13% viable sperm compared to control; P < 0.05). Thus, CLC-treated sperm showed a higher tolerance (+ 13 % sperm viability; P < 0.05) to high glycerol concentrations (5%) than non-treated sperm. Regarding the efficacy of amides as cryoprotectants, three of the amides (lactamide, acetamide and formamide) produced deleterious effects in fresh boar sperm (P < 0.05). The other amides (methylformamide, dimethylacetamide and dimethylformamide) efficiently improved post-thaw sperm viability (+ 5 to 15 %; P < 0.05) but negatively affected the sperm motility (- 11 to 16% total motile sperm; P < 0.05) and the sperm fertilizing ability in vitro (dimethylformamide: - 64 % penetration rate; P < 0.05), irrespective of the sperm treatment. On the other hand, CLC-treated samples showed better in vitro fertilizing ability than control samples when glycerol was used as cryoprotectant (+ 2 penetrated spermatozoa/oocyte; P < 0.05). The results obtained in this Thesis suggest that conventional freezing protocols should be optimized for CLC-treated boar sperm in order to obtain the benefit of CLC treatment observed in other species sensitive to cold shock. / [ES] Las inseminaciones artificiales en la especie porcina se realizan habitualmente con semen refrigerado, debido a las bajas tasas de fertilidad obtenidas con el semen congelado-descongelado. La membrana del espermatozoide sufre importantes daños cuando es sometida a la fase de enfriamiento desde la temperatura corporal hasta alcanzar los 5 ºC (choque térmico), así como durante el proceso de congelación y descongelación. El aumento del contenido de colesterol en las membranas de los espermatozoides de cerdo podría mejorar su supervivencia tras la descongelación, como sucede en otras especies sensibles al choque térmico. Este incremento en la cantidad de colesterol se puede realizar fácilmente utilizando ciclodextrinas saturadas de colesterol (CLC). El tratamiento con CLC de espermatozoides de varias especies susceptibles al choque térmico antes de la congelación ha conseguido mejorar su supervivencia tras la descongelación. En los protocolos convencionales de congelación de semen porcino se utilizan habitualmente diluyentes de congelación compuestos por yema de huevo y glicerol, sin embargo, puede que estos diluyentes de congelación convencionales no sean los más apropiados para congelar espermatozoides tratados con CLC. El objetivo de esta Tesis es evaluar la supervivencia a la congelación de los espermatozoides porcinos tratados con CLC o ciclodextrinas utilizando diluyentes de congelación convencionales, utilizando concentraciones alternativas tanto de yema de huevo como de glicerol o utilizando amidas en lugar de glicerol como crioprotectores Utilizando diluyentes convencionales, el tratamiento con 1mg de CLC o de metil-ß-ciclodextrina/120 millones de espermatozoides previamente a la congelación proporcionó una leve mejora de la integridad de la membrana plasmática espermática (+ 8%; P < 0,05) y ningún beneficio sobre la movilidad espermática (P > 0,05). Además, la respuesta al tratamiento con CLC fue similar independientemente de si los espermatozoides procedían de verracos buenos o malos congeladores (P > 0,05). Una reducción de la concentración de yema de huevo de un 20 a un 10% fue perjudicial para la supervivencia de los espermatozoides tras la descongelación, incluidos aquellos que habían sido tratados previamente con CLC (- 12% espermatozoides vivos; P < 0,05). Por otro lado, observamos que las concentraciones de glicerol utilizadas habitualmente (3%) no son las más apropiadas para congelar espermatozoides tratados con CLC (- 13 % viabilidad espermática comparando con las muestras control; P < 0,05), ya que éstos mostraron una mayor tolerancia (+ 13 % espermatozoides vivos; P < 0,05) que las muestras control a las concentraciones de glicerol más altas (5%). Con respecto a la eficacia de las amidas como crioprotectores para semen porcino, tres de las amidas (lactamida, acetamida y formamida) produjeron efectos perjudiciales durante su incubación con semen fresco (P < 0,05). El resto de amidas evaluadas (metilformamida, dimetilacetamida y dimetilformamida) mejoraron eficientemente la viabilidad espermática tras la congelación (+ 5 a 15 %; P < 0,05), sin embargo, afectaron negativamente tanto la movilidad espermática (- 11 a 16% móviles totales; P < 0,05) como la capacidad de fecundación in vitro (dimetilformamida: - 64 % en la tasa de penetración; P < 0,05), independientemente de si el semen fue tratado con CLC o no. Por otro lado, las muestras tratadas con CLC mostraron mejor capacidad de fecundación in vitro que las muestras control cuando se utilizó el glicerol como crioprotector (+ 2 espermatozoides penetrados/ovocito; P < 0,05). Los resultados obtenidos en esta Tesis sugieren que sería necesaria la adecuación de los protocolos de congelación convencionales para congelar semen porcino tratado con CLC con el propósito de alcanzar los claros beneficios obtenidos con dicho tratamiento cuando ha sido evaluado en otras especies sensibles al choque térmico. / [CA] Les inseminacions artificials en l'espècie porcina es realitzen habitualment amb semen refrigerat, a causa de les baixes taxes de fertilitat obtingudes amb el semen congelat-descongelat. La membrana de l'espermatozoide pateix importants danys quan és sotmesa a la fase de refredament des de la temperatura corporal fins a arribar als 5 ºC (xoc tèrmic), així com durant el procés de congelació i descongelació. L'augment del contingut de colesterol a les membranes dels espermatozoides de porc podria millorar la seva supervivència després de la descongelació, com succeeix en altres espècies sensibles al xoc tèrmic. Aquest increment en la quantitat de colesterol es pot realitzar fàcilment utilitzant ciclodextrines saturades de colesterol (CLC). El tractament amb CLC d'espermatozoides de diverses espècies susceptibles al xoc tèrmic abans de la congelació ha aconseguit millorar la seva supervivència després de la descongelació. En els protocols convencionals de congelació de semen porcí s'utilitzen habitualment diluents de congelació compostos per rovell d'ou i glicerol, però, pot ser que aquests diluents de congelació convencionals no siguin els més apropiats per congelar espermatozoides tractats amb CLC. L'objectiu d'aquesta Tesi és avaluar la supervivència a la congelació dels espermatozoides porcins tractats amb CLC o ciclodextrines utilitzant diluents de congelació convencionals, utilitzant concentracions alternatives tant de rovell d'ou com de glicerol o utilitzant amides en lloc de glicerol com crioprotectors Utilitzant diluents convencionals, el tractament amb 1 mg de CLC o de metil-ß-ciclodextrina / 120 milions d'espermatozoides prèviament a la congelació va proporcionar una lleu millora de la integritat de la membrana plasmàtica espermàtica (+ 8%; P <0,05) i cap benefici sobre la mobilitat espermàtica (P> 0,05). A més, la resposta al tractament amb CLC va ser similar independentment de si els espermatozoides procedien de verros bons o dolents congeladors (P> 0,05). Una reducció de la concentració de rovell d'ou d'un 20 a un 10% va ser perjudicial per a la supervivència dels espermatozoides després de la descongelació, inclosos aquells que havien estat tractats prèviament amb CLC (- el 12% espermatozoides vius; P <0,05) . D'altra banda, observem que les concentracions de glicerol utilitzades habitualment (3%) no són les més apropiades per congelar espermatozoides tractats amb CLC (- 13% viabilitat espermàtica comparant amb les mostres control; P <0,05), ja que aquests van mostrar una major tolerància (+ 13% espermatozoides vius; P <0,05) que les mostres control a les concentracions de glicerol més altes (5%). Pel que fa a l'eficàcia de les amides com crioprotectors per semen porcí, tres de les amides (lactamida, acetamida i formamida) van produir efectes perjudicials durant la seva incubació amb semen fresc (P <0,05). La resta de amides avaluades (metilformamida, dimetilacetamida i dimetilformamida) van millorar eficientment la viabilitat espermàtica després de la congelació (+ 5 a 15%, P <0,05), però, van afectar negativament tant la mobilitat espermàtica (- 11 a 16% mòbils totals; P <0,05) com la capacitat de fecundació in vitro (dimetilformamida: - el 64% en la taxa de penetració; P <0,05), independentment de si el semen va ser tractat amb CLC o no. D'altra banda, les mostres tractades amb CLC van mostrar millor capacitat de fecundació in vitro que les mostres control quan es va utilitzar el glicerol com crioprotector (+ 2 espermatozous penetrats / oòcit; P <0,05). Els resultats obtinguts en aquesta Tesi suggereixen que seria necessària l'adequació dels protocols de congelació convencionals per congelar semen porcí tractat amb CLC amb el propòsit d'assolir els clars beneficis obtinguts amb el tractament quan ha estat avaluat en altres espècies sensibles al xoc tèrmic. / Blanch Torres, E. (2015). Treating boar sperm with cholesterol-loaded cyclodextrins or cyclodextrins prior to cryopreservation: effects on post-thaw in vitro sperm quality of sperm cryopreserved in different freezing extenders [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/58773 / Compendio

Yes / Reactions have been carried out using the titanium(IV) precursors TiCl4 and Ti(OiPr)4, with addition of two equivalents of a functionalized picolinamide ligand. The reactions with TiCl4 led to the formation of either a mononuclear titanium species, [Ti(N,O)Cl2X2] or a dinuclear titanium species [Ti(N,O)X3]2[l- O] (X = OMe or Cl), with incorporation of one picolinamide ligand. The ligand is bound to the titanium centre as the protonated amide. The reactions with Ti(OiPr)4 resulted in the formation of mononuclear titanium bis-picolinamide species [Ti(N,O)2(OiPr)2], and also dinuclear and trinuclear products, [(N,O)Ti (OiPr)2][l-OiPr]2 and [(N,O)Ti(OiPr)2]2[l-OiPr]2[(OiPr)2Ti][l3-O] respectively. In these cases the picolinamide ligand was found to be deprotonated and bound to the titanium as the iminolate. These molecules have been characterized by X-ray crystallographic analysis and structural characteristics are discussed.

The purpose of this investigation was to determine the products of the electrolysis of dimethyl lithium amide. / Master of Science

La thèse décrit la première synthèse totale de l'Eucophylline, le fragment sud de l'alcaloïde Leucophyllidine récemment isolé à partir de Leuconotisgriffithii et L. eugenifolius. La synthèse en 10 étapes comprend une nouvelle méthode d’accès au squelette azabicyclo[3.3.1]nonane par un processus de carbooximation radicalaire d'oléfines à trois composants. Au cours de ces études, nous avons également isolé des énamines présentant des stabilités inhabituelles résultant de leur conformation bicyclique tendue. La synthèse de la partie éburnane, le fragment nord de la Leucophyllidine, a été réalisée grâce à une nouvelle réaction radicalaire de carbo-cyanation à trois composants. Cette réaction radicalaire s'est révélée efficace pour installer le groupement fonctionnel nitrile sur des oléfines, et éventuellement former des centres quaternaires, notamment dans des structures complexes, puisqu'une bonne tolérance aux différents groupes fonctionnels a été observée. Le couplage biomimétique entre le squelette éburnane et l'Eucophylline a finalement été étudié en utilisant des modèles de structure similaire. Les résultats préliminaires de cette étude ont montré que l'absence d'effet gem-diméthyle dans le modèle éburnane empêche probablement la formation de l'imine cyclique,intermédiaire-clé dans le couplage désiré. / The thesis describes the first total synthesis of Eucophylline, the south fragment of the Leucophyllidine alkaloid recently isolated from Leuconotis griffithiiand L. eugenifolius. The 10-step synthesis encompasses a new straight forward method to access to the azabicyclo[3.3.1]nonane skeleton through a free-radical three-component olefinic carbo-oximation process. During these studies, we also isolated enamines exhibiting unusual stabilities resulting from their strained bicyclicconformation. The synthesis of the Eburnane part, the north fragment of Leucophyllidine, was developed relying on a new free-radical three-component Carbo-Cyanation reaction. This new reaction showed high tolerance toward different functional groups and provided an efficient mean to install the nitrile group in complex structures and to introduce quaternary centers. The biomimetic coupling between the Eburnane and Eucophylline fragments was finally studied using structurally similar models. Preliminary results of this model study showed that absence of a gemdimethyleffect in the Eburnane model probably prevents the formation of the cyclicimine, key intermediate for the desired coupling.

Les hétérocycles azotés occupent une place importante en chimie organique et médicinale et, à ce titre, constituent des cibles de choix pour le développement de réactions toujours plus efficaces et faciles d’emploi. Les travaux antérieurs, réalisés au laboratoire URCOM sur l’accès aux γ-lactames, ont servi de base pour développer une méthodologie impliquant des conditions douces qui ont mis en évidence les propriétés spécifiques des N-alkoxy amides pour accéder aux γ- et δ-lactames hautement fonctionnalisés de manière hautement diastéréosélective selon un processus domino. Cette méthodologie a aussi pu être étendue aux hydantoïnes, 2-imino-thiazolidin-4-ones et thiazinan-4-ones qui constituent également des molécules étudiées en chimie médicinale. En parallèle, une comparaison de réactivité entre N-alkoxy amides et N-alkyl amides a montré la meilleure réactivité des composés N-alkoxylés pour l’obtention de ces différents hétérocycles azotés. Cette différence de réactivité a été attribuée à la possible chélation du contre anion alcalins des bases minérales utilisées dans notre approche par les N-alkoxy amides. Les conditions douces ont permis d’envisager des versions organocatalysées énantiosélectives ou multicomposantes des réactions précédentes conduisant à des résultats préliminaires intéressants. / Nitrogen-containing heterocycles are key compounds in organic and medicinal chemistry and continue to attract synthetic effort for the development of more efficient and convenient reaction. Previous work carried out at the URCOM laboratory for the access to γ-lactams has provided the basis for developing a highly diastereoselective methodology under mild conditions that has demonstrated the specific properties of N-alkoxy amides, allowing the access to γ- and δ-lactams following a domino process. This methodology also allowed the access to hydantoïns, 2-imino thiazolidin-4-ones and thiazinan-4-ones which are compounds of importance in medicinal chemistry. In parallel, a comparison of reactivity between N-alkoxy and N-alkyl amides was carried out in order to demonstrate the better reactivity of the N-alkoxy amide compounds. This better reactivity was attributed to a possible chelation of the alkali metal counter anion of the mineral bases used in our conditions by the N-alkoxy amides. These mild conditions allowed organocatalyzed enantioselective or multicomponents approaches providing interesting preliminary results.

No description available.

I found that 2.6ml of 0.5% levobupivacaine had similar clinical characteristics as the same volume of 0.5% bupivacaine in spinal anaesthesia. Both were effective for spinal anaesthesia in urological surgery, when a sensory block up to at least T10 dermatome was required. In comparing the use of levobupivacaine alone and levobupivacaine with fentanyl, there were no significant differences in haemodynamic changes and quality of sensory and motor block, when 2.6ml of levobupivacaine alone or 2.3ml of levobupivacaine with fentanyl 15mcg (0.3ml) were used in spinal anaesthesia. Both were effective for spinal anaesthesia in urological surgery. In comparing the use of ropivacaine 10mg and bupivacaine 10mg, both with fentanyl 15mcg in spinal anaesthesia for urological surgery, all the patients achieved adequate level of sensory block up to T10 dermatome or higher. The two drugs were similar in the onset time of motor block, the characteristics of sensory block and haemodynamic changes; however, the duration of motor block was shorter with ropivacaine. I concluded that both studied solutions, ropivacaine-fentanyl and bupivacaine-fentanyl, were effective for spinal anaesthesia in urological surgery and the duration of motor block was shorter with the ropivacaine-fentanyl solution. The dose-response relationship of ropivacaine in spinal anaesthesia for lower limb surgery requiring a sensory block up to at least the T12 dermatome was defined. Anaesthesia was successful in 0, 0, 42, 83 and 100% when ropivacaine at doses of 2, 4, 7, 10 and 14mg respectively were given. The derived values for ED50 and ED95 were 7.6mg and 11.4mg respectively. The cephalic level of sensory block and the degree of motor block increased with larger doses of ropivacaine. Finally, the median effective dose (ED50) of bupivacaine, levobupivacaine and ropivacaine in spinal anaesthesia for lower limb surgery were defined as 5.50mg (95% CI: 4.90--6.10mg), 5.68mg (95% CI: 4.92--6.44mg), and 8.41mg (95% CI: 7.15--9.67mg) respectively. The relative potency ratios were 0.97 (95% CI: 0.81--1.17) for levobupivacaine/bupivacaine, 0.65 (95% CI: 0.54--0.80) for ropivacaine/bupivacaine and 0.68 (95% CI: 0.55--0.84) for ropivacainellevobupivacaine. / In this series of studies, I have shown that levobupivacaine and ropivacaine are effective local anaesthetic agents for spinal anaesthesia in lower limb and urological surgery. This proved my hypothesis. Both are suitable alternatives to bupivacaine for spinal anaesthesia. Furthermore, these studies showed that ropivacaine is less potent than levobupivacaine and bupivacaine and the potency is similar between levobupivacaine and bupivacaine at median effective dose. / Levobupivacaine and ropivacaine are two relatively new local anaesthetics which were developed in view of their potential for less cardiotoxicity in comparison with bupivacaine, the most common local anaesthetic used in spinal anaesthesia for many years. Both are produced in pure S(-) enantiomer form in contrast to bupivacaine which is a racemic mixture. They have been shown to be effective in peripheral nerve blocks, and epidural analgesia and anaesthesia; nevertheless, experience of their use in spinal anaesthesia is limited. The objective of this thesis was to evaluate their use in spinal anaesthesia for surgery in non-obstetric patients. My hypothesis was that levobupivacaine and ropivacaine are effective local anaesthetic agents for spinal anaesthesia in lower limb and urological surgery. In order to test this hypothesis, I conducted five clinical studies on 269 patients who had urological surgery or lower limb surgery under spinal or combined spinal-epidural anaesthesia. First, I investigated the efficacy and clinical characteristics of levobupivacaine and the mixture of levobupivacaine with fentanyl in spinal anaesthesia. Next, I compared the use of ropivacaine-fentanyl with bupivacaine-fentanyl in spinal anaesthesia. Finally, I defined the dose-response relationship of ropivacaine in spinal anaesthesia using traditional dose-response methodology and defined the relative potency among levobupivacaine, ropivacaine and bupivacaine by comparing the defined ED50 in spinal anaesthesia using up-down sequential allocation method. / Lee, Ying Yin. / Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: . / Thesis (M.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 133-150). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.

La régulation endogène de la physiologie saisonnière, comme les rythmes circannuels et l’histoire photopériodique vécue pendant la gestation, permet aux individus d’anticiper à l’arrivée des saisons. L’objectif de cette thèse a été l’étude de l’effet de ces deux phénomènes à long terme sur les voies neuroendocrines contrôlant la physiologie saisonnière. Ces études montrent que les rythmes circannuels sont initiés au niveau de l’expression de la thyréostimuline dans la pars tuberalis et celle-ci est transmisse à l’hypothalamus où elle contrôle les niveaux d’hormone thyroïdienne et de neuropeptides. De façon similaire, la photopériode vécue pendant la gestation semble programmer l’expression des déiodinases dans l’hypothalamus des rongeurs adultes. Dans l’ensemble, ces résultats montrent la conservation du rôle de la pars tuberalis en tant que site central pour l’intégration des signaux impliqués dans le contrôle de la physiologie saisonnière. / Internal long-term timing strategies, like circannual rhythms and photoperiodic history, allow changes in physiology in anticipation to the seasons. In this project I investigated the effects of both types of history dependent timing on the neuro endocrine pathways for regulation of seasonal physiology. My work revealed that internal circannual timing is initiated through the control of thyroid stimulating hormone at the pars tuberalis and is integrated into the regulation of hypothalamic thyroid hormone levels and neuropeptides.Similarly, history-dependent expression in hypothalamic deiodinases was observed in adult rodents based on their gestational photoperiodic experience. Overall, my results highlight the pars tuberalis as a conserved central site in mammals for the integration of multiple seasonal cues, which via differential control of thyroid hormone levels in the hypothalamus dictates the timing in seasonal physiology.

Le domaine de recherche de la chimie du fluor a connu un essor considérable. En particulier, le motif SCF3 et plus récemment les groupements SCF2R (R = H, SO2Ph, SAr, COAr, Rf) ont fait l'objet d'une attention particulière de la part de la communauté scientifique du fait de leurs propriétés remarquables. Dans ce contexte, le développement de nouvelles méthodologies et de réactifs originaux pour l'introduction de ces groupements fluorés a suscité un fort intérêt. En conséquence, les objectifs de cette thèse ont été 1) de développer de nouvelles méthodologies pour la fonctionnalisation de liaisons C(sp3)-H par l'introduction directe d'un motif SCF3 catalysée par des métaux de transition, et son extension à d'autres groupements fonctionnels ainsi que 2) de concevoir et étudier de nouveaux réactifs fluorés électrophiles. La première partie de cette thèse a été dédiée au développement d'une réaction de trifluorométhylthiolation d'amides aliphatiques catalysée au palladium, une transformation inédite (Chapitre 2). Puis, la chloration d'amides aliphatiques catalysée au palladium, dans des conditions douces, a été étudiée (Chapitre 3). Enfin, une nouvelle voie de synthèse pour accéder aux sulfénamides trifluorométhylés a été développée (Chapitre 4). Cette approche a été étendue à la préparation d'un nouveau réactif électrophile pour l'introduction du groupement SCN. De plus, un réactif électrophile original, source du motif SCF2PO(OEt)2, a été synthétisé et appliqué à la construction de liaisons C-SCF2PO(OEt)2, N-SCF2PO(OEt)2 et S-SCF2PO(OEt)2 ainsi qu'à la synthèse d'un composé d'intérêt biologique (Chapitre 4). / The organofluorine chemistry field has witnessed a very fast expansion. In particular, the SCF3 moiety and more recently the SCF2R groups (R = H, SO2Ph, SAr, COAr, Rf) have attracted a special interest from the scientific community because of their remarkable properties. In this context, the development of new methodologies and original reagents for the introduction of such fluorinated groups is particularly appealing. Therefore, the goals of this thesis were 1) to develop a new methodology for the direct introduction of the SCF3 group by transition metal-catalyzed C(sp3)-H bond functionalization and its extension to other functional groups as well as 2) to design and study new electrophilic fluorinated reagents.The first part of this Ph.D. thesis was dedicated to the development of an unprecedented Pd-catalyzed trifluoromethylthiolation of aliphatic amides by C-H bond functionalization (Chapter 2). Then, the Pd-catalyzed chlorination of aliphatic amides by C-H bond functionalization under mild conditions was investigated (Chapter 3). Finally, a newly designed strategy for the synthesis of trifluoromethanesulfenamides was elaborated (Chapter 4). This approach was extended to the preparation of a new electrophilic reagent for the thiocyanation reaction. In addition, an original electrophilic SCF2PO(OEt)2 reagent was designed and applied to the construction of C-SCF2PO(OEt)2, N-SCF2PO(OEt)2 and S-SCF2PO(OEt)2 bonds as well as to the synthesis of a biorelevant compound (Chapter 4).

This thesis concerns the development of metal-free reactions to obtain carbon-heteroatom and carbon-carbon bonds. This is achieved by transferring carbon ligands from hypervalent iodine reagents to suitable nucleophiles. The bulk of the work presented herein concerns arylation of oxygen and nitrogen nucleophiles, using the well-known diaryliodonium salts as aryl sources. In the first project, O-arylation of the oxime ethyl acetohydroxamate was studied. It was found that electron-poor as well as electron-rich aryl moieties could be transferred successfully to this nucleophile. Furthermore, the protocol could be extended to a sequential one-pot synthesis of benzo[b]furans. This method allowed for a fast synthesis of the natural product stemofuran A and formal syntheses of other natural products. In a successive project, O-arylation of hydroxide and aliphatic alkoxides was investigated. It is known that electron-poor aryl moieties can be transferred to these nucleophiles in moderate to high yields. However, combined with more electron-rich diaryliodonium salts, a large amount of side products were formed. These were suppressed upon addition of aryne traps, suggesting that aryne pathways are competing with the desired ligand coupling. It was also observed that secondary alcohols were oxidized to the corresponding ketones. The mechanism for this oxidation was investigated and aryne pathways could be excluded. Instead we suggest that the carbinol hydrogen gets deprotonated via an internal mechanism, after the alkoxide has coordinated to the iodonium salt. Highly sterically congested alkyl aryl ethers could be obtained in high yields by combining tertiary alcohols with ortho-blocked diaryliodonium salts.  Next, N-arylation of secondary acyclic amides was studied using acetanilide as the model substrate. This procedure was suitable for transfer of electron-poor as well as ortho-substituted aryl moieties, but attempts to transfer very electron-rich aryl groups were unsuccessful. On the other hand, the amides displayed a complementary reactivity, allowing phenylation of electron-rich amides.  In the final project, a one-pot synthesis of the cyclic iodonium reagent vinylbenziodoxolone is presented. These compounds have not been explored as reagents earlier. Initial screenings showed that the vinyl moiety could be transferred to nitrocyclohexane with opposite regioselectivity compared to the acyclic analogue of the reagent. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 2: Manuscript.</p>