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Part A: Development of a Modular Synthetic Approach to Polycyclic Polyprenylated Acylphlorogluginols: Total Synthesis of Papuaforin A, B, C, Hyperforin and Formal Synthesis of Nemorosone. Part B: Studies Toward the Synthesis of GinkgolidesBellavance, Gabriel January 2016 (has links)
Polycyclic Polyprenylated Acylphloroglucinols (PPAPs) are a vast family of natural products, which includes more than 200 members. They contain a stunningly complex molecular architecture which in most cases includes a bicyclo[3.3.1]nonane core. PPAPs have been of interest to the scientific community for their intricate structure, their powerful aid in treating many ailments and large portfolio of biological activities. More particularly, they have been of synthetic interest since 1999 with the first report of an approach to these complicated cores by Nicolaou. Herein, we present the first total synthesis of papuaforin A, papuaforin B, papuaforin C, hyperforin and the formal synthesis of nemorosone following a report by Simpkins and co-workers. We relied on a gold(I)-catalyzed carbocyclization for the construction of the core of this family of natural products. Ginkgolides are isolated from the ginko tree, Ginkgo biloba, a living fossil with records of its existence dating back 280 million years. For centuries, the plant and its extracts have been used extensively for their beneficial properties, especially in China, Japan and India. For example, extract Egb761, one of the most potent fraction, generates over $500 million a year alone. The ginkgolides possess a truly unique compact diterpene framework of six 5-membered rings with a high content oxygen. Eleven oxygens can be found in ginkgolide C for a core containing only 23 carbons. The ginkgolides also include a very unique feature: a tert-butyl group located on the most convoluted ring system: the B ring. Few groups have found success in limning a synthetic route to ginkgolides. Corey’s group was the first to achieve the total synthesis of ginkgolide B in 1987. He was also able to complete ginkgolide A a year later. Crimmins and co-workers also achieved the total synthesis of ginkgolide B a decade later in 1999. Herein, we present our new approach toward ginkgolides through a newly developed methodology for the α-allylation of ketones and the creation of highly hindered contiguous quaternary centers. The synthesis is still at an early stage but a synthetic pathway giving access to the ring B with all the key moieties has been extensively investigated.
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Total syntheses of sanggenon-type natural products and rearrangements of 3-substituted flavone ethersXiong, Yuan 22 January 2016 (has links)
An efficient approach to the hydrobenzofuro[3,2-b]chromenone core of sanggenon-type natural products has been developed. The key transformation involves a protecting group-free double rearrangement of a bis-allyloxyflavone ether substrate. A sequence involving asymmetric 3-allyl rearrangement followed by aromatic Claisen rearrangement has been established for the asymmetric synthesis of the hydrobenzofuro[3,2-b]chromenone core structure. This methodology has been successfully applied to asymmetric syntheses of both sanggenol F and sanggenon A.
Efficient chiral, racemic syntheses for sanggenons C and O have been achieved. The key transformation entails a biomimetic Diels-Alder cycloaddition between a flavonoid diene and a 2'-hydroxychalcone. The flavonoid diene was produced from a protected flavonoid chromene via isomerization.
Metal-catalyzed alkynyl Claisen (Saucy-Marbet) rearrangements of 3-alkynyl flavone ethers have been evaluated, and a 1,2-acyl migration cascade which afforded novel furanyl benzofuranone scaffolds was discovered. Mechanistic studies have revealed that the rearrangement is likely initiated by 5-endo enyne cyclization to a platinum-containing spiro-oxocarbenium intermediate, which may be intercepted by methanol to produce a spirodihydrofuran or further rearranged to afford allenyl chromanediones and benzofuranones at higher reaction temperature. Lewis acid-catalyzed [1,3]-rearrangements of 3-aryl substituted flavone ethers have also been developed.
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The Synthesis and Structural Characterization of Main Group and Lanthanide Metal Compounds Supported by the Multidentate [N₃C] Donor Ligand tris[(1-isopropylbenzimidazol-2-yl)dimethylsilyl]methyl, [TismPriBenz]MVaccaro, David Alexander January 2023 (has links)
The Parkin group has recently synthesized tris[(1-isopropylbenzimidazol-2-yl)dimethylsilyl]methane, [TismPriBenz]H, a bulky tetradentate tripodal ligand, which upon deprotonation can coordinated to form a variety of carbatrane metal complexes.The [TismPriBenz] ligand has been previously shown to stabilize metal hydride complexes, for example [TismPriBenz]MgH and [TismPriBenz]ZnH, and the ligand also has been incorporated in complexes featuring all of the non-radioactive Group 12 and Group 13 metals, as well as a large range of transition metals. However, the reactivity of these complexes towards carbonyl compounds is largely unexplored. Additionally, beyond [TismPriBenz]Li, there has been no attempt to introduce the heavier alkali metals into the [TismPriBenz] framework, which could potentially provide more reactive starting materials to generate other previously inaccessible metal complexes of the ligand; for instance, prior to this report, there has been no example of a lanthanide complex of [TismPriBenz].
In Chapter 1, the reactivity of [TismPriBenz]MgH and [TismPriBenz]MgMe towards ketones, aldehydes, and esters is explored. Generally, these magnesium complexes are able to insert a C=O double bond into a Mg–Me or Mg–H bond respectively, providing access to a large class of magnesium alkoxides. Specifically, [TismPriBenz]MgR (R = H, Me) can insert benzaldehyde and benzophenone to give [TismPriBenz]MgOCRHPh or[TismPriBenz]MgOCRPh₂ respectively. Additionally, [TismPriBenz]MgMe has shown rare reactivity towards methyl ketones, in that it forms the magnesium enolate compounds [TismPriBenz]MgC(Me)=CH₂ and [TismPriBenz]MgC(Ph)=CH2 upon treatment with acetone or acetophenone. In fact, [TismPriBenz]MgC(Me)=CH₂ is only the fourth acetone enolate complex to be structurally characterized, and the first such magnesium example.
In the presence of the ester compounds methyl formate and ethyl acetate, [TismPriBenz]MgH and [TismPriBenz]MgMe are able to follow the insertion of the carbonyl with immediate elimination of either an aldehyde or ketone to yield the simple alkoxides [TismPriBenz]MgOMe and [TismPriBenz]MgOEt, a reaction with little precedence in the literature. [TismPriBenz]MgMe is also able to prompt the Claisen condensation of ethyl acetate, forming the first [TismPriBenz] complex with a 6-member chelating ring, [TismPriBenz]Mg(κ²-OC(Me)HC(O)OEt). These various alkoxides have demonstrated the ability to catalyze the Tishchenko reaction, the dimerization of an aldehyde to make an ester, and have also shown promise as catalysts for hydroboration and retro-aldol reactions. Lastly, the [TismPriBenz]Mg compounds have shown interesting reactivity towards O₂, leading to the isolation of both the rare peroxide dimer {[TismPriBenz]Mg}₂(μ-O₂) and the alkyl peroxide [TismPriBenz]MgOOMe.
In Chapter 2, the reactivity of the complex [TismPriBenz]Tl is further developed, providing access to previously known methyl and iodide compounds of magnesium, zinc, and cadmium. Additionally, [TismPriBenz]Tl has been shown to react directly with the alkali metals sodium, potassium, and rubidium to form the novel alkali metal complexes [TismPriBenz]M (M = Na, K, Rb). Furthermore, [TismPriBenz]Li can react with CsF to afford [TismPriBenz]Cs, completing the non-radioactive Group 1 [TismPriBenz]M series. This makes [TismPriBenz] one of only a handful of organic ligands to have structurally characterized compounds with all of the alkali metals from Li to Cs, and the only ligand that formsmonomeric complexes in each case. [TismPriBenz]K was also used as a starting material to synthesize the first [TismPriBenz] lanthanide complexes, [TismPriBenz]YbI and [TismPriBenz]YbCl₂. [TismPriBenz]YbI itself can further react with KN(SiMe₃)₂ and NaCp to give [TismPriBenz]YbN(SiMe₃)₂ and [TismPriBenz]YbCp respectively.
Lastly, the ability of the [TismPriBenz]Zn halide series to form ion pair complexes was investigated. [TismPriBenz]ZnI can react with ZnI₂ to afford {[TismPriBenz]Zn}₂[Zn₃I₈], which contains the novel zinc halide species [Zn₃I₈]²⁻. Additionally, all of the [TismPriBenz]ZnX (X = Cl, Br, I) complexes are able to react with excess ZnX₂ in THF to give the series {[TismPriBenz]Zn}[Zn(THF)X₃].
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Organokatalyse: Theoretische Untersuchungen zur Claisen-Umlagerung und zum Einfluss von Azolen auf die Morita-Baylis-Hillman-Reaktion sowie neuartige Bis(carben)metallkomplexe auf der Basis von TriazolenKirsten, Martin 02 August 2011 (has links) (PDF)
Ziel der Arbeit war es, Katalysatoren zu entwickeln, in Modellsystemen zu testen und Rückschlüsse auf deren Aktivität und Verbesserungspotential zu ziehen. Dabei standen sowohl theoretische Betrachtungen mittels quantenmechanischer Berechnungen, aber auch experimentelle Arbeiten im Mittelpunkt. Die Untersuchungen wurden an ausgewählten Beispielen der Claisen-Umlagerung und der Morita-Baylis-Hillmann-Reaktion sowie verbrückter Bis(NHC)metallkomplexe auf der Basis von Triazolen in der Mizoroki-Heck-Reaktion durchgeführt.
Claisen-Umlagerung. Die Wechselwirkung zwischen Substrat und dem Katalysator sollte hierbei auf eine bidendate Ausbildung von Wasserstoffbrücken zum Substrat entsprechend dem Design nach Jørgensen[1-4] abzielen. Die Auswahl der „Organokatalysatoren“ erstreckte sich von den Thioharnstoffen, über L-Milchsäure, einem Phosphorsäure-Derivat bis hin zu 2,2,2-Trifluorethanol (TFE).
Mit dem Allyl Vinyl Ether (AVE) 83 wurden die theoretischen Betrachtungen der Wechselwirkung und der sich daraus ergebende Einfluss auf die Umlagerungs-geschwindigkeit durchgeführt. Der Thioharnstoff 1 und dessen Wechselwirkung mit 83 standen dabei im Mittelpunkt der Betrachtungen. Es wurden zwei mögliche entscheidende Übergangszustände postuliert. Im Vergleich zum konkurrierenden Übergangszustand [s-cis-83b•1A]# war [s-trans-83b•1A]# in Summe bevorzugt. Gegenüber der thermischen Claisen-Umlagerung von 83 war [s-trans-83b•1A]# für ΔG#[3,3] um +3,1 Kcal mol-1 erniedrigt, was einer leichten Erhöhung der Umlagerungsgeschwindigkeit entsprach. Dies konnte durch experimentelle Untersuchungen bestätigt werden. Das Phosphorsäure-Derivat 94 war im Vergleich zur L-Milchsäure 91 besser in der Lage, die Barriere des sigmatropen Umlagerungsschrittes abzusenken. Es zeigte sich, dass die Kombination von 91 mit einem Wassermolekül 8 zu dem Komplex 92 zu einer verbesserten Stabilisierung des Übergangszustandes führte. Bei beiden Systemen wurde jedoch beobachtet, dass die Barrieren über den Gesamtverlauf der Reaktion nicht ausreichend stark abgesenkt werden konnten. Für die Berechnungen mit dem Lösungsmittel TFE wurde gezeigt, dass die Betrachtung der Wechselwirkung einzelner TFE-Moleküle mit dem Substrat 83 nicht ausreichte.
Morita-Baylis-Hillman-Reaktion. Mit der Morita-Baylis-Hillman-Reaktion[5, 6] (MBH) kann im Sinne einer C-C-Verknüpfungs-reaktion neben der atomökonomischen Durchführung zusätzlich ein Stereozentrum erzeugt werden. Basierend auf den Ergebnissen von Cheng et al.[7] wurde ein systematischer Zusammenhang zwischen dem eingesetzen Vermittler/Katalysator und Ausbeute/Umsatz hergestellt. Die aus der Literatur bekannte pH-Wert-Abhängigkeit der Reaktion konnte auf einen Bereich zwischen 8 und 9 eingegrenzt werden. Unter Verwendung verschiedener Substitutionsmuster am Imidazol konnte gezeigt werden, dass 1H-substituierte Imidazole die Reaktion wesentlich langsamer als die in 1-Position unsubstituierten Imidazole vermittelten, was durch DFT-Rechnungen unterstrichen werden konnte.
Im weiteren Verlauf der experimentellen Untersuchungen stellte sich heraus, dass TFE als Lösungsmittel ohne Zusatz einer weiteren Base für die Vermittlung der Reaktion gut geeignet ist.
Verbrückte Bis(NHC)metallkomplexe auf der Basis von Triazolen. Die Synthese der Bis(NHC)metallkomplexe und deren Einsatz in der Katalyse wurde von Straßner et al.[8-15] sehr intensiv studiert. Teil dieser Arbeit war es, die Bandbreite der Katalysatoren zu erweitern und den Einfluss von einem Stickstoffatom im (NHC)-Rückgrat zu untersuchen. Die synthetische Zugänglichkeit der Konstitutionsisomere wurde bereits bei der Darstellung der aromatischen Triazole gewährleistet. Die sich anschließende Darstellung der entsprechenden Salze konnte für die Methoxy-Gruppe am Aromaten erfolgreich durchgeführt werden. Die Unterscheidung von Konstitutionsisomeren eines Komplexes wurde am Beispiel von 126 und 128 durchgeführt. Hierbei zeigten sich bereits im 1H-NMR-Spektrum feine Unterschiede in den Kopplungskonstanten und auch in den Signalen für die Methylenbrücke. Der tatsächliche Beweis wurde mit der 2D-Methode, der sogenannten „Heteronuclear Multiple Bond Correlation“ – HMBC, erbracht. Der Einsatz der dargestellten Palladium(II)komplexe zeigte für p-Bromacetophenon analoge Ergebnisse zu den Imidazol-Derivaten bei „gleicher“ Konzentration. Für die Komplexe, ausgehend von den asymmetrischen Triazolen (zum Beispiel 128), wurde eine erhöhte Reaktivität beobachtet. Weiterhin wurde ein signifikanter Unterschied in der Ausbeute bei Reaktionen mit p-Chloracetophenon beobachtet.
Literatur.
[1] D. L. Severance, W. L. Jorgensen, Journal of the American Chemical Society 1992, 114, 10966.
[2] C. J. Cramer, D. G. Truhlar, Journal of the American Chemical Society 1992, 114, 8794.
[3] W. L. Jorgensen, J. F. Blake, D. Lim, D. L. Severance, Journal of the Chemical Society, Faraday Transactions 1994, 90, 1727.
[4] M. M. Davidson, I. H. Hillier, Journal of Physical Chemistry 1995, 99, 6748.
[5] A. B. Baylis, M. E. D. Hillman, (Celanese Corp.). Application: DE
DE, 1972, p. 16 pp.
[6] K. Morita, Z. Suzuki, H. Hirose, Bulletin of the Chemical Society of Japan 1968, 41, 2815.
[7] S. Luo, P. G. Wang, J.-P. Cheng, Journal of Organic Chemistry 2004, 69, 555.
[8] S. Ahrens, A. Zeller, M. Taige, T. Strassner, Organometallics 2006, 25, 5409.
[9] M. A. Taige, A. Zeller, S. Ahrens, S. Goutal, E. Herdtweck, T. Strassner, Journal of Organometallic Chemistry 2007, 692, 1519.
[10] A. Meyer, T. Strassner, unpublished results 2010.
[11] M. Taige, TU Dresden (Dresden), 2009.
[12] S. Ahrens, E. Herdtweck, S. Goutal, T. Strassner, European Journal of Inorganic Chemistry 2006, 1268.
[13] S. Ahrens, T. Strassner, Inorganica Chimica Acta 2006, 359, 4789.
[14] T. Strassner, M. Muehlhofer, A. Zeller, E. Herdtweck, W. A. Herrmann, Journal of Organometallic Chemistry 2004, 689, 1418.
[15] M. Muehlhofer, T. Strassner, W. A. Herrmann, Angewandte Chemie, International Edition 2002, 41, 1745.
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Síntese de derivados do ácido quínico, genisteína e cluvenona, potenciais agentes antimicrobianos, antitumorais e contra a esclerose múltiplaRezende Júnior, Celso de Oliveira 18 July 2014 (has links)
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Previous issue date: 2014-07-18 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Neste trabalho são descritas as sínteses e avaliações biológicas de diferentes
classes de compostos orgânicos e está dividido em três capítulos. O primeiro
deles descreve a síntese de derivados da genisteína com distintas
propriedades físico-químicas, a fim de avaliar a influência dessas
propriedades na atividade biológica contra a esclerose múltipla. Foram
sintetizados compostos condensados a carboidratos derivados da D-glicose e
D-galactose e derivados lipofílicos com cadeias alquila ou acila lineares de
doze ou quatorze carbonos. Esses compostos foram submetidos a ensaios de
citotoxicidade e anti-inflamatórios in vitro e os compostos mais ativos foram
avaliados quanto a sua atividade na modulação da resposta imune in vivo no
modelo de encefalomielite auto-imune experimental (EAE). Na síntese dos
drivados éteres verificaram-se diferentes reatividades: os compostos com
cadeias alquila lineares foram obtidos em rendimentos melhores, seguido dos
derivados da D-glicose e D-galactose, respectivamente. A regiosseletividade
obtida na síntese dos derivados éteres foi sugerida por nOe, enquanto que
nos derivados ésteres foi sugerida por RMN de 1H. Os ensaios biológicos
revelaram que todos os compostos apresentaram atividade in vitro e os
derivados de carboidrato foram mais citotoxicicos que os derivados com
cadeias lipofílicas lineares. Após os ensaios in vivo, o composto 13 foi
considerado um protótipo para o tratamento da esclerose múltipla. O
segundo capítulo descreve a síntese e avaliação das propriedades
antimicrobianas de surfactantes derivados do ácido quínico condensados a
diaminas N-alquiladas, variando-se o tamanho da cadeia alquila (parte apolar)
e a estrutura do ácido quínico (parte polar), estabelecendo-se uma relação
estrutura e atividade. Foram sintetizados 32 compostos através de reações de
amidação entre uma lactona derivada do ácido quínico com diaminas Nalquiladas
em rendimentos satisfatórios. 17 compostos apresentaram
atividades semelhantes ou melhores do que a droga de referência. Também
estão sendo realizados alguns ensaios antiparasitários e anti-inflamatórios
com esses compostos. O terceiro capítulo descreve a síntese e avaliação das
propriedades antitumorais de derivados de xantonas Garcinia,
especificamente de cluvenona. Foram sintetizados diversos compostos com
grupos retiradores e doadores de eletróns, hidrofílicos e contendo a unidade
sal de trifenilfosfônio no anel A de hidroxicluvenonas, que auxiliarão no
entendimento da relação estrutura e atividade para essa classe de
compostos. Sintetizou-se também um composto derivado da 6-
hidroxicluvenona condensada com o BODIPY com potencial atividade
antitumoral e propriedades fluorescentes com o objetivo de realizar estudos
de localização celular e mecanismo de ação. A etapa chave para a síntese
desses compostos foi uma reação em cascata de Claisen/Diels-Alder. / In this work the synthesis and biological evaluation of different classes of
organic compounds are described and it is divided into three chapters. The
first chapter describes the synthesis of genistein derivatives with different
physicochemical properties in order to assess the influence of these properties
in biological activity against multiple sclerosis. Carbohydrate derivatives from
D-glucose and D-galactose and compounds condensed with lipophilic alkyl or
acyl linear chains of twelve or fourteen carbons were synthesized. Cytotoxicity
and anti-inflammatory activities in vitro were performed and the most active
compounds were evaluated in modulating the immune response in vivo model
of experimental autoimmune encephalomyelitis. Reactivity of ethers
derivatives was different: compounds with linear alkyl chains were obtained in
higher yields, followed by the derivatives of D-glucose and D-galactose,
respectively. The regioselectivity obtained in the synthesis of ether derivatives
were suggested by nOe, while the ester derivatives were suggested by 1H
NMR. All compounds showed in vitro activity and carbohydrate derivatives
were more cytotoxic than lipophilic derivatives. After in vivo tests, compound
13 was considered a prototype for the treatment of multiple sclerosis. The
second chapter describes the synthesis and evaluation of the antimicrobial
properties of surfactants derived from quinic acid (popar part) condensates
with N-alkylated diamines (nonpolar part). The size of the alkyl chain and the
structure of quinic acid were altered, settling a relationship structure and
activity. 32 compounds were synthesized by amidation reactions between a
lactone derivative of quinic acid with N-alkylated diamines in satisfactory
yields. 17 of these compounds showed equal or better equal activities than the
drug reference. Some antiparasitic and anti-inflammatory tests are also being
conducted for these compounds.
The third chapter describes the synthesis and evaluation of antitumoral
properties of derivatives of Garcinia xanthones, specifically cluvenone. Several
compounds were synthesized with electron withdrawing and donors groups,
containing hydrophilic and the triphenylphosphonium salt unit in the A ring of
hidroxicluvenonas. These compounds will help in understanding the structure
and activity relationship for this class of compounds. A BODIPY
Hydroxicluvenone conjugate compound with potential antitumor activity and
fluorescent properties was synthesized with the aim of studying the cellular
location and mechanism of action. The key step for the synthesis of these
compounds was a reaction cascade Claisen / Diels-Alder reaction.
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Organokatalyse: Theoretische Untersuchungen zur Claisen-Umlagerung und zum Einfluss von Azolen auf die Morita-Baylis-Hillman-Reaktion sowie neuartige Bis(carben)metallkomplexe auf der Basis von TriazolenKirsten, Martin 22 June 2011 (has links)
Ziel der Arbeit war es, Katalysatoren zu entwickeln, in Modellsystemen zu testen und Rückschlüsse auf deren Aktivität und Verbesserungspotential zu ziehen. Dabei standen sowohl theoretische Betrachtungen mittels quantenmechanischer Berechnungen, aber auch experimentelle Arbeiten im Mittelpunkt. Die Untersuchungen wurden an ausgewählten Beispielen der Claisen-Umlagerung und der Morita-Baylis-Hillmann-Reaktion sowie verbrückter Bis(NHC)metallkomplexe auf der Basis von Triazolen in der Mizoroki-Heck-Reaktion durchgeführt.
Claisen-Umlagerung. Die Wechselwirkung zwischen Substrat und dem Katalysator sollte hierbei auf eine bidendate Ausbildung von Wasserstoffbrücken zum Substrat entsprechend dem Design nach Jørgensen[1-4] abzielen. Die Auswahl der „Organokatalysatoren“ erstreckte sich von den Thioharnstoffen, über L-Milchsäure, einem Phosphorsäure-Derivat bis hin zu 2,2,2-Trifluorethanol (TFE).
Mit dem Allyl Vinyl Ether (AVE) 83 wurden die theoretischen Betrachtungen der Wechselwirkung und der sich daraus ergebende Einfluss auf die Umlagerungs-geschwindigkeit durchgeführt. Der Thioharnstoff 1 und dessen Wechselwirkung mit 83 standen dabei im Mittelpunkt der Betrachtungen. Es wurden zwei mögliche entscheidende Übergangszustände postuliert. Im Vergleich zum konkurrierenden Übergangszustand [s-cis-83b•1A]# war [s-trans-83b•1A]# in Summe bevorzugt. Gegenüber der thermischen Claisen-Umlagerung von 83 war [s-trans-83b•1A]# für ΔG#[3,3] um +3,1 Kcal mol-1 erniedrigt, was einer leichten Erhöhung der Umlagerungsgeschwindigkeit entsprach. Dies konnte durch experimentelle Untersuchungen bestätigt werden. Das Phosphorsäure-Derivat 94 war im Vergleich zur L-Milchsäure 91 besser in der Lage, die Barriere des sigmatropen Umlagerungsschrittes abzusenken. Es zeigte sich, dass die Kombination von 91 mit einem Wassermolekül 8 zu dem Komplex 92 zu einer verbesserten Stabilisierung des Übergangszustandes führte. Bei beiden Systemen wurde jedoch beobachtet, dass die Barrieren über den Gesamtverlauf der Reaktion nicht ausreichend stark abgesenkt werden konnten. Für die Berechnungen mit dem Lösungsmittel TFE wurde gezeigt, dass die Betrachtung der Wechselwirkung einzelner TFE-Moleküle mit dem Substrat 83 nicht ausreichte.
Morita-Baylis-Hillman-Reaktion. Mit der Morita-Baylis-Hillman-Reaktion[5, 6] (MBH) kann im Sinne einer C-C-Verknüpfungs-reaktion neben der atomökonomischen Durchführung zusätzlich ein Stereozentrum erzeugt werden. Basierend auf den Ergebnissen von Cheng et al.[7] wurde ein systematischer Zusammenhang zwischen dem eingesetzen Vermittler/Katalysator und Ausbeute/Umsatz hergestellt. Die aus der Literatur bekannte pH-Wert-Abhängigkeit der Reaktion konnte auf einen Bereich zwischen 8 und 9 eingegrenzt werden. Unter Verwendung verschiedener Substitutionsmuster am Imidazol konnte gezeigt werden, dass 1H-substituierte Imidazole die Reaktion wesentlich langsamer als die in 1-Position unsubstituierten Imidazole vermittelten, was durch DFT-Rechnungen unterstrichen werden konnte.
Im weiteren Verlauf der experimentellen Untersuchungen stellte sich heraus, dass TFE als Lösungsmittel ohne Zusatz einer weiteren Base für die Vermittlung der Reaktion gut geeignet ist.
Verbrückte Bis(NHC)metallkomplexe auf der Basis von Triazolen. Die Synthese der Bis(NHC)metallkomplexe und deren Einsatz in der Katalyse wurde von Straßner et al.[8-15] sehr intensiv studiert. Teil dieser Arbeit war es, die Bandbreite der Katalysatoren zu erweitern und den Einfluss von einem Stickstoffatom im (NHC)-Rückgrat zu untersuchen. Die synthetische Zugänglichkeit der Konstitutionsisomere wurde bereits bei der Darstellung der aromatischen Triazole gewährleistet. Die sich anschließende Darstellung der entsprechenden Salze konnte für die Methoxy-Gruppe am Aromaten erfolgreich durchgeführt werden. Die Unterscheidung von Konstitutionsisomeren eines Komplexes wurde am Beispiel von 126 und 128 durchgeführt. Hierbei zeigten sich bereits im 1H-NMR-Spektrum feine Unterschiede in den Kopplungskonstanten und auch in den Signalen für die Methylenbrücke. Der tatsächliche Beweis wurde mit der 2D-Methode, der sogenannten „Heteronuclear Multiple Bond Correlation“ – HMBC, erbracht. Der Einsatz der dargestellten Palladium(II)komplexe zeigte für p-Bromacetophenon analoge Ergebnisse zu den Imidazol-Derivaten bei „gleicher“ Konzentration. Für die Komplexe, ausgehend von den asymmetrischen Triazolen (zum Beispiel 128), wurde eine erhöhte Reaktivität beobachtet. Weiterhin wurde ein signifikanter Unterschied in der Ausbeute bei Reaktionen mit p-Chloracetophenon beobachtet.
Literatur.
[1] D. L. Severance, W. L. Jorgensen, Journal of the American Chemical Society 1992, 114, 10966.
[2] C. J. Cramer, D. G. Truhlar, Journal of the American Chemical Society 1992, 114, 8794.
[3] W. L. Jorgensen, J. F. Blake, D. Lim, D. L. Severance, Journal of the Chemical Society, Faraday Transactions 1994, 90, 1727.
[4] M. M. Davidson, I. H. Hillier, Journal of Physical Chemistry 1995, 99, 6748.
[5] A. B. Baylis, M. E. D. Hillman, (Celanese Corp.). Application: DE
DE, 1972, p. 16 pp.
[6] K. Morita, Z. Suzuki, H. Hirose, Bulletin of the Chemical Society of Japan 1968, 41, 2815.
[7] S. Luo, P. G. Wang, J.-P. Cheng, Journal of Organic Chemistry 2004, 69, 555.
[8] S. Ahrens, A. Zeller, M. Taige, T. Strassner, Organometallics 2006, 25, 5409.
[9] M. A. Taige, A. Zeller, S. Ahrens, S. Goutal, E. Herdtweck, T. Strassner, Journal of Organometallic Chemistry 2007, 692, 1519.
[10] A. Meyer, T. Strassner, unpublished results 2010.
[11] M. Taige, TU Dresden (Dresden), 2009.
[12] S. Ahrens, E. Herdtweck, S. Goutal, T. Strassner, European Journal of Inorganic Chemistry 2006, 1268.
[13] S. Ahrens, T. Strassner, Inorganica Chimica Acta 2006, 359, 4789.
[14] T. Strassner, M. Muehlhofer, A. Zeller, E. Herdtweck, W. A. Herrmann, Journal of Organometallic Chemistry 2004, 689, 1418.
[15] M. Muehlhofer, T. Strassner, W. A. Herrmann, Angewandte Chemie, International Edition 2002, 41, 1745.
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Oxidative radical cyclisations for total synthesisFerrara, Steven January 2013 (has links)
Manganese(III) acetate mediated radical cyclisations provide a mild and powerful tool in the construction of complex bicyclic systems. This thesis focuses on the formation of a number of alkenyl substituted [3.3.0]-bicyclic γ-lactones utilising a manganese(III) acetate/copper(II) triflate induced radical cyclisation. The methodology was then applied to a short catalytic and enantioselective synthesis of (+)-aphanamol I and related natural products. Chapter 1 presents a summary of the theories and methodology which will be utilised in this work. In particular, a key focus will revolve around oxidative radical cyclisations and how manganese(III) acetate has become a vital oxidant in such areas. Chapter 2 details a catalytic and asymmetric total synthesis of (+)-aphanamol I. Following an overview of the natural product and its previous total synthesis, a racemic and asymmetric total synthesis is presented which utilises a manganese(III) acetate mediated radical cyclisation and a Claisen ring expansion as key steps. Chapter 3 reports the synthesis and subsequent cyclisation of a wide range of dienyl malonate substrates. Variation of the γ-substituent is first explored, demonstrating the effect that substituent size has on the diastereoselectivity of the cyclisation. Following this, the synthesis of [2.3.0]-,[4.3.0]- and [5.3.0]- bicyclic γ-lactones are investigated. Chapter 4 describes studies towards the total synthesis of a dolabellane natural product. Investigations into substrate synthesis which can be used in a RCM will be presented. Full experimental details and spectral data, with select NMR spectra are also provided.
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Synthetic and Theoretical Investigations of [3,3]-Sigmatropic Rearrangements and Development of Allylboration ReactionsRamadhar, Timothy Ramesar 19 December 2012 (has links)
A summary of research conducted since September 2007 at the University of Toronto in the laboratory of Professor Robert A. Batey is presented in this thesis, which is divided into four chapters. The first chapter contains a two-part introduction, where aryl- and aliphatic-Claisen rearrangements are discussed in part 1, and the nucleophilic addition of organoboron reagents to unsaturated C–N functionalities is described in part 2. Chapter 2 contains research involving synthetic and theoretical studies of aryl-Claisen rearrangements and other sigmatropic reactions. The work towards developing the lanthanide-catalyzed domino aryl-Claisen rearrangement for the synthesis of contiguous aryl–C(sp³) moieties is presented first. This is followed by computational studies involving E/Z-selectivity differences for the aryl-Claisen rearrangement, which was an issue noted for the domino aryl-Claisen reaction of a linear substrate. The mechanistic origins of E/Z-selectivity differences for the mono aryl-Claisen rearrangement, which was experimentally ambiguous for over 40 years, is resolved through computational methods. A theoretical analysis of selectivity differences for the allylic azide rearrangement is also described. The third section contains a discussion of Eu(fod)3-catalyzed aryl-Claisen rearrangements on vinyl bromide systems and preliminary studies involving application of the substrates in cross-coupling reactions, and other attempted mono- and domino sigmatropic rearrangements are presented in the fourth section. In chapter 3, the search for computational methods that can accurately predict experimental free energy of activation barriers for the aliphatic-Claisen rearrangement through benchmarking studies with a priori kinetic barrier and kinetic isotope effect data is described. Methods were found to predict new valid transition states and predict ΔG‡ values with a mean unsigned error of 0.3 kcal/mol relative to experimental values. In chapter 4, the development of new allylboration reaction is outlined, involving the double allylboration of nitriles and anhydrides, and initial studies towards the first aminoallylboration reactions of N-aluminoaldimines to form 1,2-diamines.
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Synthetic and Theoretical Investigations of [3,3]-Sigmatropic Rearrangements and Development of Allylboration ReactionsRamadhar, Timothy Ramesar 19 December 2012 (has links)
A summary of research conducted since September 2007 at the University of Toronto in the laboratory of Professor Robert A. Batey is presented in this thesis, which is divided into four chapters. The first chapter contains a two-part introduction, where aryl- and aliphatic-Claisen rearrangements are discussed in part 1, and the nucleophilic addition of organoboron reagents to unsaturated C–N functionalities is described in part 2. Chapter 2 contains research involving synthetic and theoretical studies of aryl-Claisen rearrangements and other sigmatropic reactions. The work towards developing the lanthanide-catalyzed domino aryl-Claisen rearrangement for the synthesis of contiguous aryl–C(sp³) moieties is presented first. This is followed by computational studies involving E/Z-selectivity differences for the aryl-Claisen rearrangement, which was an issue noted for the domino aryl-Claisen reaction of a linear substrate. The mechanistic origins of E/Z-selectivity differences for the mono aryl-Claisen rearrangement, which was experimentally ambiguous for over 40 years, is resolved through computational methods. A theoretical analysis of selectivity differences for the allylic azide rearrangement is also described. The third section contains a discussion of Eu(fod)3-catalyzed aryl-Claisen rearrangements on vinyl bromide systems and preliminary studies involving application of the substrates in cross-coupling reactions, and other attempted mono- and domino sigmatropic rearrangements are presented in the fourth section. In chapter 3, the search for computational methods that can accurately predict experimental free energy of activation barriers for the aliphatic-Claisen rearrangement through benchmarking studies with a priori kinetic barrier and kinetic isotope effect data is described. Methods were found to predict new valid transition states and predict ΔG‡ values with a mean unsigned error of 0.3 kcal/mol relative to experimental values. In chapter 4, the development of new allylboration reaction is outlined, involving the double allylboration of nitriles and anhydrides, and initial studies towards the first aminoallylboration reactions of N-aluminoaldimines to form 1,2-diamines.
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Catalisadores heterogêneos para produção de chalconas: reação de condensação de Claisen-Schmidt / Heterogeneous catalysts for chalcones production: Claisen-Schmidt condensation reactionWinter, Caroline 07 March 2016 (has links)
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Previous issue date: 2016-03-07 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The members of flavonoids and chalcones family have attracted great interest because of their pharmacological applications as antibacterial, anti-inflammatory and anticarcinogenicagents, and are commonly synthesized by Claisen-Schmidt condensation between acetophenone and benzaldehyde derivatives. This reaction is usually catalyzed under homogeneous conditions which present, however, several drawbacks such as catalyst recovery and waste disposal problems. This work proposes the use of a variety of heterogeneous catalysts to achieve good results for condensation Claisen-Schmidt reaction in terms of conversion and chalcones selectivity, when compared to the homogeneous catalysis. Two groups of catalysts were tested: metal oxides and activated carbons. Magnesium oxide catalysts were prepared by hydrothermal treatment and magnesium, niobium, lanthanum and titanium oxides by rehydration of commercial precursors, all methods followed and not followed by cesium impregnation. The activated carbons used as catalysts were Babassu, Bahia Coconut, ox bone and Dendê, raw and treated with sodium hydroxide. The catalysts were characterized by scanning and transmission electron microscopy, thermogravimetric analysis, differential thermal analysis, determination of the specific superficial area by the adsorption/desorption of N2 at 77 K method, infrared spectroscopy, X-ray diffraction and temperature-programmed desorption of CO2 and NH3. The basic sites of carbons were quantified by Boehm Method. Finally, the performance of the catalysts was evaluated on the Claisen-Schmidt reaction between Acetophenone and 4-nitrobenzaldehyde, and the conversion was quantified by high performance liquid chromatography. The best catalyst was treated babassu activated carbon, whose conversion achieved was 92,38%. / Os membros da família das chalconas e flavonóides têm despertado um grande interesse devido às suas aplicações como agentes farmacológicos, antibacterianos, anti-inflamatórios e anticarcinogênicos, sendo comumente sintetizados via condensação de Claisen-Schmidt entre derivados de acetofenona e de benzaldeído. Esta reação é catalisada normalmente sob condições homogêneas, que apresentam, no entanto, vários inconvenientes, tais como a recuperação do catalisador e problemas de destinação de resíduos. Neste trabalho foi proposto o uso de uma série de catalisadores heterogêneos para se alcançar bons resultados para a reação de condensação de Claisen-Schmidt, em termos de conversão e seletividade de derivados de chalconas, quando comparados à catálise homogênea. Foram testados dois grupos de catalisadores: óxidos metálicos e carvões ativados. Prepararam-se catalisadores de óxido de magnésio por tratamento hidrotérmico e óxidos de magnésio, nióbio, lantânio e titânio por reidratação de precursores comerciais, todos os métodos seguidos e não seguidos por impregnação de césio. Os carvões ativados utilizados como catalisadores foram de babaçu, coco da Bahia, osso de boi e dendê brutos e tratados com hidróxido de sódio. Os catalisadores foram caracterizados por microscopia eletrônica de varredura e transmissão, análise termogravimétrica, análise térmica diferencial, determinação de área superficial específica por análise textural de adsorção/dessorção de N2 a 77 K, espectroscopia de infravermelho, difração de raios X e dessorção à temperatura programada de CO2 e NH3. Os sítios básicos dos carvões foram quantificados pelo método de Boehm. Finalmente, o desempenho dos catalisadores foi avaliado na reação de Claisen-Schmidt entre Acetofenona e 4-Nitrobenzaldeído, sendo a conversão quantificada por cromatografia líquida de alta eficiência. O melhor catalisador foi o de carvão de babaçu tratado, cuja conversão alcançada foi de 92,38%.
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