Dissertations / Theses on the topic 'Azetines'
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1
Luheshi, Abdul-Basset Nuri. "Cycloadditions to 1-azetines and 1-azetin-4-ones." Thesis, University of Salford, 1988. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327973.
2
Hemming, Karl. "Studies in the chemistry of 1-azetines and 1-azetin-4-ones." Thesis, University of Salford, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334307.
3
O'Gorman, P. A. "Some aspects of the chemistry of small ring organic molecules : 1-azetines, 1-azetidinones, 3-oxo-β-sultams and cyclopropenones." Thesis, University of Huddersfield, 2009. http://eprints.hud.ac.uk/id/eprint/6310/.
Abstract:
The -lactams and the related -sultams are attractive targets for synthesis because of their central importance in antibiotics such as the penicillins. These heterocycles are of further interest because of their potential as inhibitors of the serine protease class of enzymes113, believed to be responsible for diseases such as rheumatoid arthritis and cystic fibrosis. This thesis will describe the synthesis of the 4-vinyl beta lactams (A)25, thiation of these compounds using Lawesson’s reagent to yield thio lactams (B) and subsequent conversion into the corresponding 1-azetine (C) using Meerwein’s reagent. Compound (C) provided a template for a series of cycloaddition reactions in order to produce a series of bicyclic heterocycles, represented by general structure (D). One reaction that was explored in this series was that between 1-azetines (C) and diphenylcyclopropenone (DPP) (E) which should have yielded the bicyclic adducts F). 93 In the event the products isolated were not the anticipated cycloadducts (F) but rather the ring expanded compounds (G)114 obtained via sigmatropic rearrangement, the nucleus of which is an isomer of the azabicyclononane system, present in many important72 alkaloids such as anatoxin-a (H) and pinnamine (I). The project subsequently evolved to look at the possibility of synthesising other alkaloid nuclei such as the pyrrolizidines, indolizidines and pyrroloazepines through the reaction of the appropriate imines with cyclopropenones. These bicyclic systems are present in many natural products72 such as pyrrolam A (J) and indolizidine 223AB (K) and are of great interest for synthesis because of the wide range of biological activities they possess, such as the ability to block the nicotinic receptor channels. This thesis will therefore describe an effective synthesis of the heterocycles shown in Scheme A (where n = 1, 2 or 3). Further research into the reactions of 4-vinyl -lactams (A) has also been conducted with a view to synthesising analogues of the pyrrolobenzodiazepine, antitumour, antibiotic natural products, of which DC-81 (L) is an example.115 Thus, reaction of (A) with o-azidobenzoylchloride gave the N-substituted -lactam (M). Ring closure via an azide-alkene cycloaddition and loss of nitrogen gave either the aziridine compound (N) or the methyl imine (O). Overall the work described in this thesis pioneers initial research into the reactions of electron rich imines with cyclopropenones, positively demonstrating their use in the synthesis of analogues of alkaloid natural products.
4
Pitard, Arnaud. "1-azetines, 1,2-thiazetin-1,1-dioxides and isothiazol-1,1-dioxides as building blocks in heterocyclic synthesis : the attempted synthesis of bicyclic β-sultams." Thesis, University of Huddersfield, 2009. http://eprints.hud.ac.uk/id/eprint/7061/.
Abstract:
This thesis is concerned with the synthesis of β-sultams and the development of new routes for the synthesis of bicyclic versions of these molecules as potential anti-bacterials. The synthesis of 1-azetines, 1,2-thiazetin-1,1-dioxides and isothiazol-1,1-dioxides as precursors of bicyclic heterocycles is described. 1-Azetines were synthesised from azetidin-2-ones prepared via the [2+2] cycloaddition of alkenes with N-chlorosulfonyl isocyanate (CSI). They reacted with diphenylcyclopropenone or nitrile oxides to afford bicyclic systems whose reactivity was explored and afforded a range of heterocycles such as 1,2,4-oxadiazoles, pyridines or pyrimidines via novel reaction pathways. The synthesis of 1,2-thiazetin-1,1-dioxide through two routes will be discussed: the alkylation of 3-oxo-β-sultams to afford 3-ethoxy-1,2-thiazetin-1,1-dioxides, and the ring contraction of an isothiazol-1,1-dioxide to afford a 3-diethylamino-1,2-thiazetin 1,1-dioxide. The reactivity of these 1,2-thiazetin-1,1-dioxides towards diphenylcyclopropenone, 1,3-dipoles and dienes was studied and is fully described. In the course of chemistry mentioned above, a series of isothiazol-1,1-dioxides was synthesised. Their reaction with 1,3-dipoles to yield the corresponding bicyclic heterocycles is described.
5
Losa, Romain. "Organocatalyse redox par les phosphines : découverte de nouvelles transformations et vers le développement d'une version électrocatalytique." Electronic Thesis or Diss., université Paris-Saclay, 2024. http://www.theses.fr/2024UPASF014.
Abstract:
Les recherches effectuées dans le cadre de cette thèse se sont portées sur l'organocatalyse par les phosphines trivalentes, des composés jouant un rôle crucial dans de nombreuses transformations chimiques et largement employées dans des synthèses organiques efficaces et variées. L'un des deux axes de recherche de cette thèse s'est concentré sur le développement de nouvelles méthodologies organocatalysées par les phosphines trivalentes. Notre intérêt s'est porté sur des procédés P(III)/P(III) ou P(III)/P(V) permettant la synthèse d'hétérocycles oxygénés ou azotés. Après avoir élaboré une version stœchiométrique en phosphine, nous avons optimisé la méthodologie en la rendant catalytique. Une étude plus approfondie permettant la synthèse de dérivés 2-azétines promue puis catalysée par les phosphines a été développée durant cette thèse. Les produits ainsi obtenus ont pu être valorisés en synthèse organique et testés biologiquement. Enfin, le second axe de recherche mené au cours de cette thèse s'est directement focalisé sur l'électroréduction des oxydes de phosphine cycliques. Dans le contexte environnemental actuel et à la vue des préoccupations écologiques, il est impératif de rendre catalytique en phosphore les réactions promues par les phosphines en introduisant un réducteur dans le milieu réactionnel. Afin d'aller vers le développement de réactions électro-catalytiques, nous avons donc utilisé l'électrochimie pour la réduction des oxydes de phosphine, inscrivant ainsi nos travaux dans une démarche de chimie plus vertueuseThis thesis work focused on organocatalysis using trivalent phosphines, compounds which play a crucial role in many chemical transformations and widely used for several organic syntheses. One of the two research axes of this thesis focused on the innovative development of organocatalytic methodologies using trivalent phosphines. We focused on P(III)/P(III) or P(III)/P(V) processes for the synthesis of oxygen or nitrogen-containing heterocycles. After developing a version stoichiometric in phosphine, the methodology was optimized by making it catalytic. A more detailed study enabling the synthesis of 2-azetine derivatives, promoted and then catalysed by phosphines, was developed during this thesis. The products thus obtained were valued in organic synthesis and tested biologically. Finally, the second line of research in this thesis focused directly on the electroreduction of phosphine oxides. In today's environmental context, it is imperative to render the reactions promoted by phosphine catalytic in phosphine, by introducing a reducing agent into the reaction medium. In order to progress towards the development of electrocatalytic reactions, we used electrochemistry for the reduction of phosphine oxides, thus inscribing our work in a more virtuous chemistry approach
6
Pearson, Christopher I. "Lithiated azetidine and azetine chemistry." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:cf3c942f-80de-4092-a38d-11006ccbb9ce.
Abstract:
This work describes developments in new azetidine and azetine chemistry; specifically, methods developed for the introduction of functionality α- to nitrogen in both ring systems, with additionally in situ formation of the latter system, from azetidine substrates. Chapter 1 discusses the growing importance of azetidines, and the current methods available for making substituted azetidines by ring formation. Further discussion comprises of current sp3 C–H activation approaches α- to nitrogen in heterocyclic compounds as potential methods for sp3 C–H activation on azetidines to give substituted azetidines. Previous work by the Hodgson group in this area is detailed. Chapter 2 describes the advance made towards 2,3-disubstituted azetidines using the thiopivaloyl protecting/activating group, where the latter plays a key role. Optimisation, scope, selectivity and mechanistic insight into the α-deprotonation–electrophile trapping of a 3-hydroxy azetidine system is discussed, which successfully gives access to a range of 3-hydroxy-2-substituted azetidines. Preliminary investigations with 3-alkyl-2-substituted azetidines are also described. Chapter 3 describes the development of a straightforward protocol to make 2-substituted-2- azetines, a rarely studied and difficult to access 4-membered azacycle subclass, from readily accessible azetidine starting materials using α-deprotonation–in situ elimination followed by further α-lithiation–electrophile trapping. Extension of this methodology by transmetallation from the intermediate organolithium to the organocuprate, resulting in greater electrophile scope, is also described.
7
Yoshizawa, Akina. "Azetidines for asymmetric synthesis." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8719/.
Abstract:
The creation of asymmetric ligands with lower environmental impact is important, as such chiral N,N' ligands attract some attention. A new method for the synthesis of 1,2,4-trisubstituted amino azetidines with \(cis\) relative configuration across its two stereogenic centres was reported in 2013. Due to this \(cis\) conformation, the azetidine compounds are expected to be good chiral ligands for asymmetric catalysis. The nitro aldol (Henry) reaction is an established method for producing new carbon-carbon bonds and is a key reaction in the synthesis of many important compounds. Enantioselective Henry reactions generate carbon-carbon bonds and our azetidines are probed as ligands for that reaction. In this work, new azetidines and their palladium and platinum complexes were prepared and characterised by techniques including X-ray diffraction, confirming retention of the \(cis\) conformation. Furthermore, enantiopure \(cis\)-azetidines were used as chiral ligands for a range of transition metals including the use of Cu-azetidine complexes as catalysts for the Henry reaction, in up to >99.5% ee. New enantiopure amino azetidines and their transition metal complexes are demonstrated as asymmetric catalysts for the asymmetric Henry reaction.
8
Thaxton, Amber. "Synthesis of Novel Azetidines." ScholarWorks@UNO, 2013. http://scholarworks.uno.edu/td/1764.
Abstract:
Azetidine is a four-membered nitrogen-containing heterocyclic ring that has recently received a great deal of attention as a molecular scaffold for the design and preparation of biologically active compounds. Structure-activity studies employing functionalized azetidines have led to the development of variety of drug molecules and clinical candidates encompassing a broad spectrum of biological activities.
Herein, the synthesis a novel series of 3-aryl-3-arylmethoxyazetidines is described. Selected 3-aryl-3-arylmethoxyazetidines were evaluated for their binding affinity to multiple monoaminergic transporters for the potential treatment of methamphetamine addiction. It was discovered that this scaffold exhibits high binding affinity (nM) for both the serotonin and dopamine transporters. In addition, a new method was developed for the synthesis of 3,3-diarylazetidines. This new approach provides a facile and efficient method to synthesize a variety of diaryl heterocycles including 3,3-diarylazetidines, 3,3-diarylpyrrolidines, and 4,4-diarylpiperidines in moderate to good yields.
9
Kloesges, Johannes. "Novel Chemistry of aziridines and azetidines." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.509969.
10
Pancholi, Alpa Kishor. "Synthesis of substituted azetidines and spirocyclic diazetidines." Thesis, University of Warwick, 2017. http://wrap.warwick.ac.uk/102606/.
Abstract:
Chapter 1 begins with an introduction to azetidines, including a discussion of the methodologies for their synthesis, their applications, relevance in natural products and as building blocks in medicinal chemistry. It then describes the development of a new asymmetric route to 2-substituted azetidin-3-ones using Enders’ SAMP/RAMP auxiliary. A one-pot process was developed involving the metalation of SAMP hydrazones of N-Boc-azetidin-3-one, alkylation and subsequent in situ hydrolysis to give the substituted products. Various bases and reaction conditions were explored to find optimal conditions for maximal yield and enantioselectivity. A representative range of electrophiles were screened including alkyl, allyl and benzyl halides and carbonyl compounds, producing enantioselectivities of up to 85% ee. Multiple substitution on the azetidin-3-one ring was briefly explored by repetition of the alkylation/hydrolysis sequence. Derivitisation by way of Pictet-Spengler reactions was used to confirm the absolute configuration at the newly created stereocentre. Chapter 2 begins with an introduction to 1,2-diazetidines outlining methods for their synthesis, before introducing the relevance of these nitrogen spirocycles. This chapter then describes two routes for the synthesis of these novel spirocyclic 1,2- diazetidines by (i) formation of the diazetidine ring and (ii) functionalisation of a range of 3-methylene-1,2-diazetidines including differentially protected variants. The diazetidines were subjected to dichloro- and difluorocyclopropanation with the latter achieved in high yields. Additionally, reactions with tetracyanoethylene by way of highly asynchronous [2π+2π] cycloadditions proceeded in near quantitative yield. In this way, a range of novel 4,5-diazaspiro[2.3]hexane and 1,2- diazaspiro[3.3]heptane spirocycles were produced. Chapter 3 details the experimental procedure and characterisation for all the novel compounds synthesised.
11
PORTAL, MARTINE. "Syntheses de pyrrolidines et azetidines polyfonctionnalisees homochirales d'interet biologique." Paris 6, 1993. http://www.theses.fr/1993PA066211.
Abstract:
Les pyrrolidines polyhydroxylees chirales jouent un role biologique important en agissant principalement comme inhibiteurs de glycosidases, antibiotiques, antidiabetiques, insecticides. L'acces aux pyrrolidines et aux azetidines polyhydroxylees a ete realise a partir de produits naturels peu onereux. Dans le chapitre i, nous presentons la synthese du 2,5-dideoxy-2,5-imino-d-mannitol (dmdp, inhibiteur de glucosidases) et d'un diastereoisomere, le 2,5-dideoxy-2,5-imino-l-iditol, a partir du seul d-mannitol. Dans le chapitre ii, nous presentons la synthese de l'acide 3-hydroxy-azetidine-2-carboxylique, -amino acide non proteinique et unite chirale, composante de l'acide 3-hydroxymugineique (phytosiderophore) ainsi que l'aldehyde correspondant, a partir du diethyl-l-tartrate. Enfin, dans le chapitre iii, nous proposons la synthese d'un precurseur de la (-) anisomycine (antibiotique) a partir du l-arabinose
12
Feula, Antonio. "Synthesis of azetidines and pyrrolidines : towards medicinal chemistry and organocatalysis applications." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/4214/.
Abstract:
Room temperature iodocyclisation of homoallylamines stereoselectively delivers functionalised 2- (iodomethyl)azetidine derivatives in high yield. Increasing reaction temperature from 20 °C to 50 °C switches the reaction outcome to realise the stereoselective formation of functionalised 3-iodopyrrolidine derivatives. It was shown that these pyrrolidines are formed via thermal isomerisation of the aforementioned azetidines. Primary and secondary amines could be reacted with iodomethyl azetidine derivatives to deliver stable methylamino azetidine derivatives. With subtle changes to the reaction sequences homoallyl amines could be stereoselectively converted to either cis- or trans- substituted 3-amino pyrrolidine derivatives at will. The stereochemical divergent synthesis of cis and trans substituted pyrrolidines supports an ion part, aziridinium, isomerisation pathway for azetidine to pyrrolidine isomerisation. Six azetidine derivative were probed in a zebrafish embryo developmental assay for capacity to illicit morphological changes. The range of effects across the probed molecules demonstrates the suitability of this assay for screening azetidine derivatives. One of the probed molecules, rac-(((cis)-1-benzyl-4-phenylazetidin-2-yl)methyl)piperidine, exhibited particularly promising effects in the developmental assay.
13
Michaud, Thierry. "Synthese d'heterocycles azotes enatiomeriquement purs (aziridines, azetidines, isoxazoles) au depart de monosaccharides." Clermont-Ferrand 2, 1995. http://www.theses.fr/1995CLF21711.
Abstract:
Un axe important de la chimie des glucides est leur utilisation comme source de chiralite dans la synthese de molecules a proprietes biologiques potentielles. Notre objectif a ete la synthese d'azetidines polyhydroxylees substituees en 2 et 3, enantiomeriquement pures, au depart de monosaccharides. Des ditosylates en 4,6 ont ete prepares en quatre etapes au depart des d-gluco- et d-mannopyranose par acetalisation, c-alkylation, hydrolyse et tosylation. Dans la serie du d-glucopyranose l'action d'amines primaires (methyl-, benzyl-, et tertbutylamine) sur les derives ditosyles permet d'acceder, par l'intermediaire d'un derive monoamine en 6 et monotosyle en 4, a des azetidines fusionnees en 4,6 a un galactopyranoside. Huit azetidines fusionnees ont ete ainsi preparees. Le deblocage des fonctions alcoolprotegees sous forme d'ethers benzyliques, et l'ouverture du cycle pyranose par l'hydrogene en presence d'hydroxyde de palladium sur charbon active conduit a des azetidines polyhydroxylees optiquement pures possedant quatre centres asymetriques. Dans la serie du d-mannopyranose, l'action de la terbutylamine conduit au seul derive 4,6-didesoxy-4,6diaminod-talopyranoside. Les reactions de cycloaddition dipolaire 1,3 des methyl-et benzonitriloxydes sur la 3-bromolevoglucosenone sont regioselectives et conduisent a des isoxazoles fusionnes et substitues en 5 par le groupe carbonyle
14
UNGUREANU, IONA MARIA. "La reactivite des aziridines et azetidines revisitee ou nouvelles voies d'acces aux heterocycles." Université Louis Pasteur (Strasbourg) (1971-2008), 2000. http://www.theses.fr/2000STR13083.
Abstract:
Dans certaines conditions la phenyl-n-tosyl-aziridine et son homologue superieur, la 2-phenyl-n-tosyl-azetidine se comportent comme des precurseurs de dipoles 1,3 et 1,4 respectivement. Ces dipoles non classiques reagissent avec des doubles liaisons activees (allylsilanes, dihydropyrane, enamines cycliques) ou non activees (cycloacenes, methylencycloalcanes, etc. ) pour donner generalement des produits de cycloaddition 3 + 2 et 4 + 2 dipolaire. Cette reactivite represente une nouvelle voie rapide et efficace pour la synthese des pyrrolidines et piperidines polysubstituees. Si globalement, la reactivite de la phenyl-n-tosyl-aziridine et de la 2-phenyl-n-tosyl-azetidine sont apparentes, des differences sensibles peuvent etre remarquees dans certains cas. Ces differences semblent etre dues au comportement specifique des especes 1,5 et 1,6 dipolaires formees au cours de la reaction. Des aspects mecanistiques relativement complexes ont ete elucides.
15
Baeg, Jin-Ook. "Palladium(II)-catalyzed regiospecific and stereospecific cycloaddition reactions of aziridines and azetidines with heterocumulenes." Thesis, University of Ottawa (Canada), 1995. http://hdl.handle.net/10393/9676.
Abstract:
A study has been made of cycloaddition reactions of 3- and 4-membered ring nitrogen-containing heterocycles with heterocumulenes in the presence of Pd(II) catalyst. Bis(benzonitrile)palladium dichloride, Pd(PhCN)$\sb2$Cl$\sb2$, smoothly catalyzes the completely regioselective reactions of 1,2-disubstituted aziridines with N,N-diarylcarbodiimides to give imidazolidinimines in high yield. Similar cycloaddition reactions involving 1,2,3-trisubstituted aziridines and heterocumulenes (carbodiimides, isocyanates and isothiocyanates) provide regio- and stereospecific routes to imidazolinimines, imidazolidinones, and thiazolidinimines. Pd(PhCN)$\sb2$Cl$\sb2$-catalyzed cycloaddition reactions of chiral, optically active 1,2-disubstituted aziridines with heterocumulenes proceed with retention of configuration affording the corresponding five-membered ring heterocycles in high yield and in optically pure form. The study of the reaction of aziridines with N,N-diarylsulfurdiimide in the presence of a Pd(II) catalyst resulted in the discovery of a new and unusual cyclization furnishing imidazolidinethiones. Cycloaddition reactions of azetidines with heterocumulenes (carbodiimides and isothiocyanates) are also catalyzed by Pd(PhCN)$\sb2$Cl$\sb2$ and afford tetrahydropyridin-2-imines and tetrahydro-1,3-thiazine-2-imines, respectively, in a regio- and stereospecific manner in excellent yield. On the basis of results obtained, including spectroscopic studies and X-ray analysis, a mechanism has been proposed for the cycloaddition reactions of the N-heterocycles with heterocumulenes. A bis(azetidine)palladium complex was isolated and shown to be catalytically active for the reaction of azetidines with heterocumulenes. Numerous heterocyclic compounds have been prepared for the first time, some of them having the potential for pharmacological activity.
16
Hama, Salih Mariwan Abdulla. "Synthesis of azetidines, γ-lactams, fused furan bispyrrolidines and 2-pyrazolines : towards medical application." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6838/.
Abstract:
Azetidines are important class of heterocyclic organic compounds in drug discovery and natural product synthesis. Several natural products and pharmaceuticals are containing azetidine precursors such as, penaresidin and Azelnidipine. Iodine mediated cyclisation of homoallylamines were found to furnish iodoazetidines at 20 °C and further reaction with amine nucelophiles afforded aminoazetidines in high yields. The cyclisation of various homoallylamines which different substitution patterns using molecular iodine to furnish new classes of compounds with interesting biological applications were studied. The iodocyclisation of 3-methyl substituted homoallylamine were found to deliver γ-lactam compound in moderate yield as a mixture of diastereoisomers, the reaction conditions were optimised, and the separation into single diastereoisomers and modification in to pyrrolidine ring were investigated. The tricyclic furan bispyrrolidines were obtained in relatively low yields when 3-phenyl substituted homoallylamines were cyclised using the same strategy. The cyclisation of homoallylhydrazines to deliver pyrazoline compounds in high yield was studied in detail. Finally, the biological activity of some of the synthesised compounds were investigated in zebrafish embryo developmental assays and showed intriguing biological responses. Some of the synthesised compounds were sent to Syngenta and Lilly Company for further investigation.
17
Rabasso, Nicolas. "Nouvelles méthodologies pour la synthèse enantioselective d'hétérocycles azotés de quatre à huit chainons." Paris 6, 2003. http://www.theses.fr/2003PA066274.
18
Odom, Lindsay D. "Reactions of diazoketones catalyzed by rhodium (II) : synthesis of functionalized azetidines and tetrahydrofurans as potential protein kinase C inhibitors /." Full text available from ProQuest UM Digital Dissertations, 2006. http://0-proquest.umi.com.umiss.lib.olemiss.edu/pqdweb?index=0&did=1331395991&SrchMode=1&sid=8&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1218744025&clientId=22256.
19
Slaughter, Kimari. "Synthesis and Development of Potential CB1 Receptor Neutral Antagonists." ScholarWorks@UNO, 2012. http://scholarworks.uno.edu/td/1483.
Abstract:
Cannabis and its derivatives have been used for both medicinal and recreational purposes. The study of this plant led to the discovery of over 60 cannabinoids, found exclusively in cannabis, that contribute to the behavioral effects of cannabis use, the most common is delta-9-tetrahydrocannabinol. Cannabinoid receptors function to increase activity in the mesolimbic dopamine reward system. Dopamine is a neurotransmitter that plays a major role in addition and its regulation plays a crucial role in mental and physical well-being. There is evidence that CB1 receptors are important to the reinforcing effects and the development of physical dependence on opiate drugs. Studies have shown that increased levels of dopamine are consistent with addiction while reduced levels lead to a decline in recreational use.
The goal of this research is to design, synthesize and develop potential CB1 receptors that exhibit a neutral cannabinoid antagonist pharmacological profile.
20
Barré, Baptiste. "Fonctionnalisation d'hétérocycles par des réactions métallo-catalysées." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066461.
Abstract:
Les réactions de couplage croisé ont révolutionné la chimie organique. Par exemple, dans le domaine de la chimie médicinale, les réactions de couplage sont de puissants outils pour générer rapidement et facilement une librairie de composés. Depuis la découverte des premières réactions de couplage croisé catalysé par des complexes de palladium, ce métal reste le plus utilisé. Cependant, d’autres métaux tels que le cuivre, le nickel, le cobalt ou le fer sont apparus comme de bonnes alternatives aux complexes de palladium, chers et toxiques.D’autre part, en chimie médicinale, les hétérocycles sont des motifs essentiels puisqu’ils sont présents dans un grand nombre de médicaments. Le développement de nouvelles méthodes permettant de former des molécules incorporant des motifs hétérocycliques tels que des azétidines, des pyrrolidines ou des oxétanes, est un réel défi pour un chimiste organicien. Les halogénures d’alkyle sont généralement des substrats difficiles à utiliser en couplage croisé car l’addition oxydante du métal y est difficile. Des réactions parasites peuvent également avoir lieu telles que des réactions de -H élimination ou de déshalogénation. Cependant, les sels de cobalt et de fer se sont révélés être des catalyseurs efficaces pour réaliser des réactions de couplage sur des halogénures d’alkyle. Au cours de cette thèse, deux systèmes catalytiques à base de sels de cobalt ou de fer ont été développés pour réaliser des réactions de couplage croisé entre des halogénures d’alkyle hétérocycliques et des réactifs de Grignard. Une étude mécanistique des réactions de couplage croisé catalysé par des sels de cobalt a également été réaliséeCross-coupling reactions, as Prof. K. C. Nicolaou said “have changed the way we think about synthesis”. Indeed, cross-coupling reactions are powerful tools to access easily and rapidly to a library of compounds in the context of medicinal chemistry. Palladium-catalysed cross-coupling rules the field and was recognized by the Nobel Prize in 2010 but, since its discovery, others metals have appeared as good alternatives to the expensive and toxic palladium salts such as copper, nickel, cobalt and iron salts. In medicinal chemistry, heterocycles are essential moieties since they are found in a great number of drugs on the market. It is always a challenge for organic chemists to develop new methods to produce motifs with interesting pharmacological properties such as substituted azetidines, pyrrolidines and oxetanes. sp3 Halides are challenging substrates for cross-coupling because the oxidative addition of the metal in the C-X bond is difficult and because side reactions can take place like -hydride elimination or dehydrohalogenation. Nevertheless, cobalt and iron are suitable catalysts to perform cross-coupling reactions on sp3 halides. Herein, we would like to report two catalytic systems allowing the cross-coupling between heterocyclic alkyl halides and Grignard reagents using cobalt and iron salts. A mechanistic study on cobalt-catalysed cross-coupling reaction between halides and Grignard reagents will be also presented
21
Nocquet, Pierre-Antoine. "Vers la synthèse d'une nouvelle classe d'iminosucres conformationnellement contraints : ouverture d'azétidines, cyclisation 4-exo-trig et C-H amination catalytique." Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAF047/document.
Abstract:
De précédentes études dans notre groupe ont montré que l'α-1-C-nonyl-1,5-didésoxy-1,5-imino-D-xylitol était un inhibiteur puissant de la β-glucocérébrosidase, enzyme impliquée dans la maladie de Gaucher. Il a été supposé que la conformation chaise inversée de ce composé pouvait expliquer en partie sa forte affinité avec la glycosidase cible. L'objectif ce travail de thèse était la synthèse d'une nouvelle classe d’iminosucres, basée sur un squelette 1-azaspiro[3.3]heptane, possédant deux cycles à 4 membres, analogue conformationnellement contraint de notre "lead" en série iminoxylitol. La première stratégie de synthèse envisagée a permis de mettre en avant une nouvelle réaction tandem d'ouverture d'azétidines conduisant à des spirocyclopropyl γ-lactames. La seconde stratégie testée a conduit dans un premier temps à la formation hautement stéréosélective d'un cyclobutane tétrasubstitué par une réaction radicalaire induite par le SmI2 − permettant ainsi la synthèse des premiers exemples de carbasucres à 4 membres − puis à la formation du carbone azaspiranique de notre cible par une réaction de C-H amination catalysée par des complexes de rhodiumPrevious studies in our group has shown that α-1-C-nonyl-1,5-dideoxy-1,5-imino-D-xylitol was a strong inhibitor of β-glucocerebrosidase, the enzyme involved in Gaucher disease. It was supposed that the inverted chair conformation of this compound could partially explain its high affinity with the target glycosydase.The goal of this PhD work was the synthesis of a new class of iminosugars based on 1-azaspiro[3.3]heptane structures, as conformationally strained analogues of our lead in the iminoxylitol series. During the course of our synthetic study, new azetidine ring-opening tandem reaction leading to spirocyclopropyl γ-lactames has been discovered. The most promising strategy evaluated led to the highly stereoselective formation of a tetrasubstituted cyclobutane via a SmI2-mediated radical reaction − leading to the synthesis of the first exemples of 4-membered carbasugars − then to the formation of the azaspiranic carbon of our target by way of rhodium-catalyzed C-H amination reaction
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Kern, Nicolas. "Réactivité d'azacycles en catalyse à l'or." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAF012/document.
Abstract:
La catalyse organométallique est l'un des piliers de la synthèse chimique moderne. Elle permet notamment la formation rapide de liaisons carbone-carbone et carbone-hétéroatome, processus les plus importants pour la fabrication des milliers de composés nécessaires à la vie contemporaine. Elle répond également aux critères d'économie d'atomes et d'énergie, et de réduction des déchets, des risques et des coûts de mise en oeuvre d'une réaction chimique.Parmi les thématiques les plus récentes de la synthèse organique, la catalyse homogène à l'or s'est imposée en seulement quelques années comme un outil synthétique très puissant. Elle autorise la génération rapide de complexité moléculaire à partir de substrats simples par l'activation d'insaturations carbonées. Durant ces études, nous avons tenté de tirer profit du caractère carbophile des complexes d'or (1) et (Ill) mais aussi de leur affinité pour certaines fonctions polaires pour transformer des hétérocycles acétyléniques en composés hétéropolycycliques dans des réactions en cascade. La réactivité complémentaire des complexes d'argent (1) a également été exploitée, ces derniers présentant de surcroît une sélectivité remarquable pour la déprotection d'éthers de méthoxybenzyleOrganometallic catalysis is a key tool of modern chemical synthesis. lts use is ubiquitous in the preparation of bulk or fine chemicals, in particular for the assembly of carbon-carbon and carbon-heteroatom bonds. Besides its overall efficiency, it responds to the responsible criteria of energy and atom economy, the reduction of waste, risk, and financial costs needed to perform a chemical reaction.ln just a few years, homogenous gold catalysis has emerged as an invaluable tool for the fast generation of molecular complexity. lndeed, it allows the strong electrophilic activation of unsaturated hydrocarbon moieties (e.g. alkynes or alienes). During this PhD thesis, we focused our studies on the use of gold's pi acidity as weil as its "classical" - but less discussed - Lewis acid character for the triggering of cascade reactions.Starting from acetylenic heterocycles, we targeted the synthesis of polycyclic compounds. The milder reactivity of silver complexes was also found useful in these reactions, as weil as in the deprotection of methoxybenzyl ethers
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Malik, Sarika. "Application of sulfur ylides in the synthesis of dihydrobenzofurens and azetidines." Thesis, 2009. http://localhost:8080/iit/handle/2074/3692.
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Arora, Anjali. "Studies towards the synthesis of Azetidines using sulfur ylides and related compounds." Thesis, 1994. http://localhost:8080/iit/handle/2074/3535.
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Sharma, Raman Lata. "Student on the reaction of Sulfur ylides with Aziridines and related compounds-an approach to azetidines." Thesis, 1989. http://localhost:8080/iit/handle/2074/3502.