Made available in DSpace on 2016-08-29T15:35:33Z (GMT). No. of bitstreams: 1 tese_6839_Deborah Araujo dos Santos.pdf: 4163979 bytes, checksum: 0617c463dfaf8e4aa093f0b0ccd941c1 (MD5) Previous issue date: 2013-08-30 / O presente estudo tem como objetivo avaliar o uso do pentacloreto de nióbio (NbCl5) como catalisador em reações de Diels-Alder entre o anel furano e alguns dienófilos reativos. Alguns parâmetros como, temperatura, tempo reacional e proporção de catalisador foram variados a fim de se encontrar as melhores condições reacionais para cada par dieno/dienófilo. Os compostos de nióbio apresentam acidez de Lewis comprovada por vários estudos. Em especial, o NbCl5 demonstrou boa atividade como catalisador em diversas reações orgânicas. Desde a sua descoberta em 1928, a cicloadição [4+2], ou reação de Diels-Alder é amplamente estudada e utilizada na construção de anéis de seis membros. O notável interesse nessas reações se dá devido à possibilidade de se obter moléculas com elevada complexidade estrutural em apenas uma etapa reacional. A reação de Diels-Alder empregando o anel furano como dieno fornece o 7-oxabiciclo[2.2.1]hept-5-eno, um intermediário na síntese de diversos produtos naturais como derivados do ácido chiquímico, terpenos, prostaglandinas, entre outros. Um problema associado a essas reações é a baixa reatividade do furano como dieno, com isso diversos estudos vem propondo o uso de catalisadores ácidos de Lewis e pressões elevadas com o intuito de melhorar os rendimentos reacionais e a seletividade. Nas reações em que o furano foi o dieno e o acrilato de metila o dienófilo, rendimentos maiores que os descrito na literatura foram obtidos especialmente a baixas temperaturas; o NbCl5 não foi ativo em nenhuma das condições reacionais testadas com o maleato de dimetila; nas reações em que a acrilonitrila participou como dienófilo os rendimentos foram baixos e observou-se a formação de subprodutos, possivelmente resultado de polimerização; as reações com a 2-cloro-crilonitrila também apresentaram rendimentos baixos, mas com inversão da seletividade em relação ao observado para os outros adutos; e com base em um estudo teórico reportado na literatura, realizou-se uma tentativa de efetuar uma hetero Diels-Alder com o acetaldeído como heterodienófilo, entretanto há evidências da formação do produto de substituição no anel. Quando o 2-metil-furano foi o dieno as reações apresentaram subprodutos, não havendo formação do cicloaduto.

Orientador: Luiz Carlos Dias / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-07-27T12:27:35Z (GMT). No. of bitstreams: 1 Jardim_LucianaSouzaAlcantara_M.pdf: 4196341 bytes, checksum: 398ae80b24af861d0f39c00e3509f71c (MD5) Previous issue date: 2000 / Mestrado

The inverse demand hetero Diels-Alder reaction has been shown to be catalysed by commercially available, air-sensitive lanthanide Lewis acid catalysts such as Yb(fod)₃ . To date there have been no reported examples of enantioselective Lewis acid catalysed reactions of ethyl vinyl ether with crotonaldehyde, the inverse demand hetero Diels-Alder reaction of interest. This Diels-Alder reaction yields dihydropyran products which are key in the synthesis of a number of natural product target molecules, such as carbohydrates. The lack of stereospecificity achieved with known chiral NMR shift reagents has been attributed to fluxional behaviour of the ligands on the large lanthanide metal centre. This lack of conformational rigidity was proposed to be controlled by the use of sterically demanding C₃ symmetric multidentate ligand systems. By carefully designing a suitable ligand system the binding of the crotonaldehyde moiety in the Lewis acid catalysed reaction was anticipated to occur with facial selectivity, resulting in enantioselective Diels-Alder products. It was determined that lanthanide complexes of fluorinated β-diketone ligands with sufficiently low pKa's effectively catalyse the desired inverse demand hetero Diels-Alder reaction. These functionalities were incorporated into a multidentate, achiral, C₃ symmetric ligand system which upon lanthanide complexation was shown to be an air-stable efficient Lewis acid catalyst. Two chiral C₃ symmetric ligand systems were also prepared but were shown to be unsuitable for lanthanide substitution due to insufficiently robust functionalities present in the ligand framework, such as sulfonyl esters and Molecular modelling studies of these ligand systems reveal that the incorporation of camphor into the ligand framework is ideal for the preparation of a facially selective aldehyde binding site. Thus, concluding work probed other possible ligand functionalities which would result in camphor containing, chiral, C₃ symmetric ligand systems that are stable as lanthanide Lewis acid complexes. This new class of ligand promises to be of interest as chiral C₃ symmetric ligand systems for substitution on lanthanide metal centres have yet to be reported. This work summarises several useful synthetic strategies for the preparation of chiral C₃ symmetric ligands in multigram quantities. The application of these higher order symmetry ligands in enantioselective catalysis remains an important area of research. / Graduate

This thesis describes tin and non-tin mediated approaches towards the total synthesis of chaetochalasin A 1 through an intramolecular domino Diels-Alder approach, and subsequent synthesis of the Diels-Alder analogues exo NH 13E-272, endo NH 13E-273, exo NH 13Z-287 and endo NH 13Z-288 through an intramolecular Diels-Alder approach.The initial tin mediated route involved the initial formation of alcohol 119, which exhibited a 2,4-syn methyl arrangement, put in place through the use of two chiral auxiliary mediated asymmetric alkylations. Subsequent functionalisation of alcohol 119 led to aldehyde 215, which incorporated a vinyl stannane functional group. The α,β-unsaturated aldehyde 215 was then reacted with β,γ-BT-sulphone 120 under trans selective Julia conditions to give predominantly the (1E,7E,9E,11E) isomer of vinyl stannane 117. However, subsequent Stille reactions to form the Z,E diene functional group, between vinyl stannane 117 and vinyl iodide 118 resulted in a product that exhibited extreme isomerisation of the triene functional group.A subsequent non-tin mediated route involved the synthesis of aldehyde 229 from alcohol 119, which then underwent a trans selective Julia olefination with BT-sulphone 120 to give predominantly the (2E,8E,10E,12E) isomer of ester 228. Ester 228 was then converted into aldehyde 227, which then underwent a Z-selective olefination to put in place the 2Z,4E diene of methyl ester 226. Further functionalisation of methyl ester 226 using past methodology within the Thomas group led to pyrrolinone 110. Subsequent small scale attempts to convert pyrrolinone 110 into chaetochalasin A 1 through a domino Diels-Alder reaction proved ineffective.Formation of the exo NH 13E-272, endo NH 13E-273, exo NH 13Z-287 and endo NH 13Z-288 Diels-Alder analogues involved the initial conversion of alcohol 119 into aldehyde 275, followed by trans selective Julia olefination with BT-sulphone 120 to give predominantly the (4E,10E,12E,14E) isomer of ester 274. Further functionalisation of ester 274 using past methodology within the Thomas group, led to pyrrolinone 243, which then underwent an intramolecular Diels-Alder reaction to give the 13E : 13Z isomers in a 1 : 1 ratio, with each isomer exhibiting an exo : endo geometry in a 5 : 4 ratio.

Swerilactones and related natural products were isolated from the plant Swertia mileensis and related species from the Gentianacea family. All members have shown moderate bioactivity in a hepatitis B virus assay. Despite their appealing framework and bioactivity, to date no syntheses of these compounds have been reported in the literature. All members of the natural products family display a polycyclic framework, containing lactone-pyran fused bicyclic subunits, and are heavily oxygenated. En route to swerilactones A and B, featuring a complex pentacyclic (6/6/6/6) ring system, the successful syntheses of two key building blocks for studies of a biomimetic [4+2] cycloaddition have been accomplished. The challenges associated with the design of a novel synthesis of a 2H-pyran diene are presented and ultimately relied on a Saucy-Marbet rearrangement of a propargyl vinyl ether. Reactivity studies for the 2H-pyran have shown thermal normal demand and photoinduced, radical cation [4+2] cycloadditions are Diels-Alder modes of choice, whereas inverse demand pathways were unproductive. Synthetic routes to obtain carboxylate and various enol ether substituted dienophilic lactones are also outlined. They relied on a unified strategy, comprised of the rapid assembly of a β-brominated sorbate derivative via cross-couplings and final oxa-6π electrocyclization as an original ring closure strategy. Our attempts at coupling the 2H-pyran intermediate with the dienophilic lactones to access the core structure of swerilactones A and B, leveraging our preliminary reactivity studies are presented in detail. In addition, alternatives strategies to assemble the core structures of swerilactones A and B are described, along with our efforts (and potential routes) toward related members of this family of natural products.

Large scale chemical reaction networks are a ubiquitous phenomenon, from the metabolism of living cells to processes in planetary atmospheres and chemical technology. At least some of these networks exhibit distinctive global features such as the “small world” behavior. The systematic study of such properties, however, suffers from substantial sampling biases in the few networks that are known in detail. A computational model for generating them is therefore required. Here we present a Toy Model that provides a consistent framework in which generic properties of extensive chemical reaction networks can be explored in detail and that at the same time preserves the “look-and-feel” of chemistry:  Molecules are represented as labeled graphs, i.e., by their structural formulas; their basic properties are derived by a caricature version of the Extended Hückel MO theory that operates directly on the graphs; chemical reaction mechanisms are implemented as graph rewriting rules acting on the structural formulas; reactivities and selectivities are modeled by a variant of the Frontier Molecular Orbital Theory based on the Extended Hückel scheme. The approach is illustrated for two types of reaction networks:  Diels−Alder reactions and the formose reaction implicated in prebiotic sugar synthesis.

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The introductory chapter reviews the current state of mechanistic understanding of the hexadehydro-Diels-Alder (HDDA) reaction. With the rapid development of the HDDA reaction from its first discovery in 1997, the question of whether a concerted or stepwise mechanism better describes the thermally activated formation of ortho-benzyne from a diyne and a diynophile has been debated. Mechanistic and kinetic investigations were able to show that this is not a black or white situation, as minor changes can tip the balance. In chapter 2 of this thesis, the catalytic process leading from 1,11-bis(p-tolyl)undeca-1,3,8,10-tetrayne to fully-substituted naphthalene and azulene derivatives, by two different platinum-catalyzed dimerization pathways, was investigated. In chapter 3, the cannibalistic self-trapping reaction of an ortho-benzyne derivative generated from 1,11-bis(p-tolyl)undeca-1,3,8,10-tetrayne in an HDDA reaction was investigated. Without adding any specific trapping agent, the highly reactive benzyne is trapped by another bisdiyne molecule in at least three different modes. In chapter 4 direct UV/VIS spectroscopic evidence for the existence of an o-benzyne in solution is reported, and the dynamics of its formation in a photo-induced reaction are established. For this purpose, 1,11-bis(p-tolyl)undeca-1,3,8,10-tetrayne was investigated, using femtosecond transient absorption spectroscopy in the ultraviolet/visible region. In chapter 5, following the isolation and characterization of the reaction products discussed in chapter 3, further species resulting from reactions of the highly reactive ortho-benzyne derivative were identified. / Das einleitende Kapitel gibt einen Überblick über den aktuellen Stand des mechanistischen Verständnisses der Hexadehydro-Diels-Alder (HDDA)-Reaktion. Mit der rasanten Entwicklung der HDDA-Reaktion seit ihrer ersten Entdeckung im Jahr 1997 wurde die Frage diskutiert, ob ein konzertierter oder ein schrittweiser Mechanismus die thermisch aktivierte Bildung von ortho-Benzin aus einem Diin und einem Diinophil besser beschreibt. Mechanistische und kinetische Untersuchungen konnten zeigen, dass es sich hierbei nicht um eine Schwarz-Weiß-Situation handelt, da schon kleine Änderungen das Gleichgewicht verändern können. In Kapitel 2 dieser Arbeit wurde der katalytische Prozess, der von 1,11-Bis(p-tolyl)undeca-1,3,8,10-tetrain zu vollständig substituierten Naphthalin- und Azulen-Derivaten führt, über zwei verschiedene platinkatalysierte Dimerisierungspfade untersucht. In Kapitel 3 wurde die kannibalistische Selbsteinfangreaktion eines ortho-Benzin-Derivats untersucht, das aus 1,11-Bis(p-tolyl)undeca-1,3,8,10-tetrain in einer HDDA-Reaktion erzeugt wurde. Ohne Zugabe eines spezifischen Einfangmittels wird das hochreaktive Benzin von einem anderen Bisdiin-Molekül in mindestens drei verschiedenen Modi eingefangen. In Kapitel 4 wird der direkte UV/VIS-spektroskopische Nachweis für die Existenz eines o-Benzins in Lösung berichtet und die Dynamik seiner Bildung in einer photoinduzierten Reaktion aufgezeigt. Zu diesem Zweck wurde 1,11-Bis(p-tolyl)undeca-1,3,8,10-tetrayne mittels Femtosekunden-Transienter-Absorptionsspektroskopie im ultravioletten/sichtbaren Bereich untersucht. In Kapitel 5 wurden nach der Isolierung und Charakterisierung der in Kapitel 3 diskutierten Reaktionsprodukte weitere Spezies identifiziert, die aus Reaktionen des hochreaktiven ortho-Benzin-Derivats resultieren.

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No description available.