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1
Ishaq, Salma. "New substrates for Pauson-Khand reaction." Thesis, University College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428148.
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Kaufmann, Karina Anne Celia. "A study of the Pauson-Khand reaction." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486323.
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The introduction to this thesis commences with a description of the mechanism of the Pauson-Khand reaction (PKR) as postulated by Magnus. Three examples of biologically active compounds synthesised using the stoichiometric PKR are presented, and the cobalt catalysed PKR is surveyed together with the asymmetric cobalt catalysed PKR. The first half of Chapter 2 describes research into the reaction pathway of a cobalt catalysed asymmetric PKR. Three enynes 68, 81 and 82 were synthesised together with the novel alkyne 80. Compounds 68, 80, 81 and 82 were used to synthesise the novel (BINAP)(enyne)C02(CO)4 complexes 89-92. X-Ray crystal structures were obtained for novel complexes 89 and 90. Variable temperature 31p NMR experiments were first carried out on complexes 89, 91 and 92 under nitrogen and all four complexes (89-92) were examined in the same way under an atmosphere of carbon monoxide. The variable temperature 31p NMR experiments under carbon monoxide with novel complexes 89, 91 and 92 resulted in the observation of a new resonance at 0 54 ppm. Observation of the resonance at 0 54 was found to be dependant on the presence ofan alkene moiety within the complexes. A (J bonded cobalt-alkyne complex (93) was identified by X-ray crystallography, which stimulated the synthesis of two enynes 94 and 95, containing internal alkyne moieties. Novel (BINAP)(enyne)C02(CO)4 complexes 98 and 99 were synthesised from enynes 94 and 95 and subjected to variable temperature 31p NMR experiments under carbon monoxide whereupon the new resonance at 054 was observed. The novel (BINAP)Co(CO)(CI) complex 100 was isolated and examined by X-ray crystallography, and the resonance at 0 54 was characterised by NMR spectroscopy and X-ray crystallography as the novel HCo(COh(BINAP) complex 101. The enynes (89, 91 and 92), water and the Pauson-Khand adduct 69 were investigated as a hydrogen source for the formation of complex 101 but the search was inconclusive. 31p NMR spectroscopy of the catalytic PKR revealed the presence of 101 in the PKR together with (BINAP)C02(CO)6 75. The second half of Chapter 2 describes the application of the catalytic PKR in the synthesis of drug candidates. Three reversible covalent inhibitors of cathepsin Sand K enzymes were designed. The development of a new intermolecular PKR utilising alkene reactants tert-butyl-2,5-dihydropyrrole carboxylate 124 and tert-butyl-2,3-dihydropyrrole carboxylate 125 was a~empte~.. An intramole~u~ar PKR was used to synthesise five potential inhibitor sequences, U8a-e, which exhibited poor selectlvity and low inhibition of the cathepsin Sand K enzymes.
3
Lindsay, David Montgomery. "Development of the asymmetric Pauson Khand reaction." Thesis, University of Strathclyde, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248568.
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Sezer, Serdar. "Remote Control Of The Diastereoselectivity In The Pauson." Phd thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613908/index.pdf.
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In this thesis, an intramolecular Pauson-Khand reaction of chiral enynes
derived from homoallyl, allyl and homopropargyl alcohols is described. For this
purpose, 2-heteroaryl substituted homoallyl, allyl and homopropargyl alcohols are
easily and efficiently resolved through enzymatic resolution in a high ee (91-99%)
with a known stereochemistry. Each enantiomerically enriched enyne derived from
homoallyl and homopropargyl alcohols affords the conformationally most stable
diastereomeric cyclopenta[c]pyran ring system as a sole product, whereas
enantiomerically enriched enynes derived from allyl alcohols give the diastereomeric
cis:trans mixture of cyclopenta[c]furan ring system. In addition these, an
intramolecular Pauson&ndashKhand reaction of camphor tethered enynes derived from homoallyl, homomethallyl, and homopropargyl alcohols is also described. Accordingly, homoallyl, homomethallyl, and homopropargyl moieties are easily constructed on the camphor carbonyl group with excellent diastereoselectivity due to endo-face selectivity, and with known stereochemistry. Each enantiomerically pure enyne affords the conformationally most stable diastereomeric spirocyclic cyclopenta[c]pyran ring system.
5
Robert, Frédéric. "Utilisation de diphosphinoamines dans la réaction Pauson-Khand." Université Joseph Fourier (Grenoble), 1999. http://www.theses.fr/1999GRE10241.
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La reaction de pauson-khand est une des methodes les plus efficaces pour la formation de cyclopentenones. La reaction etant catalysee par des complexes de dicobalt, nous avons entrepris une etude sur la substitution de deux monoxydes de carbone du complexe par des diphosphinoamines pontant les deux atomes de cobalt. Tout d'abord, l'utilisation de substituants electroattracteurs sur les phosphores a augmente le pouvoir accepteur des phosphines. Cela a favorise le depart de monoxyde de carbone, stabilise les complexes et augmente les rendements de la reaction de pauson-khand. D'autre part, l'introduction de chiralite sur le ligand, sur l'amine puis sur les substituants du phosphore, a ouvert la voie pour une nouvelle approche asymetrique de la reaction. Sous pression de monoxyde de carbone, les diphosphinoamines ont permis l'utilisation d'une quantite catalytique de complexe en reaction intermoleculaire. Des problemes concernant le mecanisme et la regioselectivite observee et les moyens mis en uvre pour tenter d'y repondre ont aussi ete abordes.
6
Verdaguer, i. Espaulella Xavier. "Reaccions de Pauson-Khand amb alcoxialquins derivats d'alcohols quirals." Doctoral thesis, Universitat de Barcelona, 1994. http://hdl.handle.net/10803/667766.
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Se han estudiado las reacciones intramoleculares de Pauson-Khand de los eteres 3-alcoxialil propargílicos y 3-alcoxipropargil alílicos derivados del 2-neopentiloxi-3-bornanol y del 3-neopentiloxi-iso-borneol. Las diastereoselectividades observadas en las reacciones de estos sistemas llegó hasta 14/1 (aproximación del inductor unido al alquino).
Se ha abordado, también, el estudio de la inducción asimétrica en las reacciones intermoleculares de Pauson-Khand y en este contexto se diseñó y preparó un nuevo tipo de auxiliar quiral quelante. Las reacciones del complejo de dicobaltohexacarbonilo del 10-metiltio-iso-borniloxietino con olefinas tensionadas transcurre con elevada selectividad. En el caso del norbornadieno se llegó al 91% D.E.. En ambas aproximaciones, la intra y la intermolecular, se recuperaron los auxiliares quirales con excelentes rendimientos, y se determinaron las configuraciones absolutas de los respectivos aductos de Pauson-Khand.
7
Blunt, Gillian. "Developing novel synthetic methods for the Pauson Khand reaction." Thesis, University of Glasgow, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248289.
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8
Fjermestad, Torstein. "Computacional studies on the mechanism of the pauson-khand reaction." Doctoral thesis, Universitat Rovira i Virgili, 2010. http://hdl.handle.net/10803/9112.
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La aplicación de los métodos de la química computacional ha llevado a una mejor comprensión del mecanismo de la reacción de Pauson-Khand para la síntesis de ciclopentenonas, en especial en su variante enantioselectiva. Se han analizado tres métodos distintos para introducir enantioselectividad en esta reacción, que en su modelo original no es selectiva. Se han estudiado tres casos: a) la activación del catalizador convencional dicobalto octacarbonilo mediante un N-óxido quiral, b) la modificación de este mismo catalizador mediante la sustitución de dos ligandos carbonilo por una difosfina quiral, y c) la sustitución del catalizador dinuclear de cobalto por un catalizador mononuclear de rodio con ligandos quirales.
El estudio teórico ha llevado a la caracterización de aspectos mecanísticos que son inaccesibles al estudio puramente experimental, y contribuye así al desarrollo de métodos catalíticos más eficientes para esta importante reacción.
The application of computational methods has lead to a better understanding of the mechanism of the Pauson-Khand reaction (PKR) for the synthesis of cyclopentenone compounds. In particular the enantioselective PKR has been considered.
Different methods for inducing enantioselectivity in this originally unselective reaction have been analyzed. Three cases have been considered: a) Activation of the conventional dicobalt octacarbonyl catalyst by a chiral N-oxide, b) A modification of the dicobalt catalyst by means of a substitution of two carbonyl ligands by a chiral diphosphine ligand. and c) the substitution of the dinuclear cobalt catalyst by a mononuclear rhodium catalyst with chiral ligands.
The theoretical study has lead to the characterization of mechanistic aspects that would be inaccessible from a purely experimental study. The study therefore contributes to the development of more efficient catalytic methods for this important reaction.
9
Miller, Ian. "The application of temporary tethers to the Pauson-Khand reaction." Thesis, University of Exeter, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.421557.
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Lewis, Sara Estelle. "Probing the role of phosphines in the Pauson-Khand reaction." Thesis, King's College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407447.
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11
Ratcliffe, Paul David. "Solution and solid-phase amine N-oxide promoters for use in metal-mediated organic synthesis." Thesis, University of Strathclyde, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275147.
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12
Solà, i. Oller Jordi. "Lligands hemilàbils en la reacció de Pauson-Khand intermolecular i asimètrica." Doctoral thesis, Universitat de Barcelona, 2006. http://hdl.handle.net/10803/2802.
Full textAbstract:
La reacció de Pauson-Khand (PK) és formalment una cicloaddició 2+1+1 entre un alquè, un alquí i una molècula de monòxid de carboni per donar lloc a una ciclopentenona. Aquesta reacció està mediada per una espècie de cobalt (0). El primer pas de la reacció és la formació d'un complex de dicobalthexacarbonil de l'alquí, d'estructura tetrahèdrica (per reacció entre l'alquí i Co2(CO)8). La posterior coordinació i inserció de l'olefina acabarà donant lloc a la ciclopentenona final. En aquesta reacció es poden formar fins a dos nous centres quirals de manera que és necessària la introducció d'un element quiral per controlar l'estereoquímica de la reacció. La coordinació amb un lligand quiral és l'aproximació més elegant per a desenvolupar versions asimètriques de la reacció. Dins del camp dels lligands destaquen els lligands bidentats P,S (PuPHOS i CamPHOS) desenvolupats al nostre grup de recerca. Aquets lligands es coordinen a un complex de cobalt en forma de pont, mitjançant el fòsfor i el sofre, donant lloc a dos diastereòmers. Cada un d'aquests diastereòmers reacciona amb elevada selectivitat amb olefines tensionades obtenint els corresponents adductes amb elevats excessos enantiomèrics.Els lligands bidentats PuPHOS i CamPHOS estudiats consten en la seva estructura d'un carboni unit a tres heteroàtoms (P, O, S) fet que confereix certa acidesa al protó que sustenta. Per tant, aquest protó pot establir una interacció estabilitzant per pont d'hidrogen 'no clàssic' amb un grup acceptor adequat, contingut en l'estructura de l'alquí. Degut a la quiralitat intrínseca dels lligands, aquesta interacció només és possible en un dels dos diastereòmers de manera que es produeix un reconeixement eficaç entre el lligand i el complex de cobalt. Com a acceptors de pont d'hidrogen s'han emprat amb èxit complexos d'amides i sulfones. D'aquesta manera s'obtenen elevats excessos diastereomèrics (de fins el 99%) en la reacció d'intercanvi de lligand. Els estudis realitzats per 1H-RMN, difracció de raig X i càlculs teòrics del complexos obtinguts confirma l'existència d'un enllaç d'hidrogen no clàssic entre el lligand i el grup acceptor de pont d'hidrogen (en els diastereòmers majoritaris). D'altra banda, els càlculs teòrics realitzats situen aquest enllaç dins el camp de les interaccions per pont d'hidrogen no clàssiques més fortes. La posterior reacció de Pauson-Khand dels complexos majoritaris obtinguts transcorre amb elevada selectivitat amb el norbornadiè. S'obtenen els adductes corresponents amb bons rendiments (fins el 99%) i excel·lents excessos enantiomèrics (fins el 99%).
Per una altra banda s'ha sintetitzat una nova família de lligands: N-fosfinosulfinamides. Aquest tipus de compostos es troba descrit a la literatura. Aquests nous lligands, quirals en l'àtom de sofre, es coordinen també en forma de pont sobre els complexos de cobalt d'alquins mitjançant els àtoms de sofre i fòsfor. És el primer cop que es descriu la coordinació de compostos tipus sulfòxid a cobalt mitjançant l'àtom de sofre. La reacció de coordinació transcorre amb rendiments molt bons i selectivitats molt elevades, fins i tot en alquins no funcionalitzats (fins a 20:1 r.d.). La reacció de Pauson-Khand dels diastereòmers majoritaris, aïllables per cristal·lització en la majoria de casos, té lloc amb excel·lents rendiments i enantioselectivitats (fins a 99% de rendiment i 99% d'ee.).
"Hemilabile Ligands in the Pauson-Khand reaction".
The Pauson-Khand reaction is a cycloaddition, promoted or catalysed by cobalt, between an alkene and an alkyne with insertion of a carbon monoxyde molecule to give a cyclopentenone. If the olefin is disubstituted, two new stereogenic centres can be created. Among the ligands designed for this reaction, we must highlight the CamPHOS and the PhuPHOS ligands. They are bidentate P, S ligands. When coordinated to a bimetallic cobalt complex, a bridged structure where the sulphur and the phosphorus are coordinated to different metal atoms is obtained.
A unique methine moiety attached to three heteroatoms (O, P, S) and contained in the PuPHOS and CamPHOS ligands can serve as a strong hydrogen-bond donor. Nonclassical hydrogen bonding of this methine with an hydrogen-bond acceptor provides a completely diastereoselective ligand exchange process between an alkyne dicobalthexacarbonyl complex and a phosphine ligand. This weak contact has been studied by means of X-ray analysis, 1H NMR, and quantum mechanical calculations and revealed that thepresent interaction falls in the range of strong C-H···O bonds. The hydrogen-bond bias obtained in the ligand exchange process has been exploited in the asymmetric intermolecular Pauson-Khand reaction to yield the corresponding cyclization adducts in up to 99% ee.
Finally, a new family of chiral ligands for the asymmetric PK reaction was synthesized . Starting from the known (R)-(+)- tert-butyl tert-butanethiosulfinate the corresponding tert-butylsulfinamides can be achieved. Deprotonation with BuLi at low temperature, alkylation with diphenylphosphine chloride yielded the desired ligands. In order to avoid the internal oxygen transfer a protection-deportection step as borane complexes must be included. After heating a dicobalt hexacarbonyl complex in toluene in presence of these new ligands two tetracarbonyl diastereomers are formed. The yields and diasereoselectivities obtained were excellent even when unfunctionalized alkynes were used. Thus mixtures of diastereomers in a 6:1 to 20:1 ratio are obtained in 50-80% yields. The Pauson-Khand reaction of the major diastereomers obtained with norbornadiene proceeded with excellent yields and enantiomeric excesses.
Thus, in some cases quantitative yields and up to 99% ee are obtained in some cases.
13
Pallerla, Mahesh Kumar. "Strain as a design principle stereoselective Pauson-Khand reactions of cyclopropenes /." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 274 p, 2008. http://proquest.umi.com/pqdweb?did=1456289601&sid=4&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Stevenazzi, Andrea. "Cobalt(0) carbonyl complexes as catalysts for the Pauson-Khand reaction." Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.397812.
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Khaizourane, Héléa. "Intermolecular Pauson-Khad reaction: study of the regioselectivity, photochemistry of the adducts and synthetic applications." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/396319.
Full textAbstract:
The Pauson-Khand reaction (PKR), introduced by Pauson and Khand in 1973, is an efficient method to access the synthesis of five-membered rings in one single step. This reaction is a transition metal-mediated [2+2+1] carbocyclisation between an alkyne, an alkene and carbon monoxide (CO). It forms a cyclopentenone where two new asymmetric centres would be created if the alkene is disubstituted. This reaction is commonly mediated by a cobalt complex such as Co2(CO)8.
In the intermolecular PKR, when the synthesis involves terminal alkynes, the reaction is highly regioselective affording a single cyclopentenone with the substituent in a to the carbonyl group. However, the regiochemical outcomes of the PKR of unsymmetrical internal alkynes are difficult to predict since it can afford two regioisomers, a/f3.
The first objective of the doctoral thesis was to better understand and predict the regioselectivity of the intermolecular PKR.
We have successfully carried out a study using a full set of aliphatic alkynes bearing sterically similar but electronically different substituents. Indeed, the influence of the electronic effects over the regioselectivity of the intermolecular PKR of aliphatic alkynes has been predicted by theoretical calculations of the alkyne. Thus, when substituents bearing more electronegative atom than the carbon, -I groups yielded tofi —regioisomer with a remarkably high regioselectivity. While a less electronegative atom than the carbon inverted the regioselectivity toward the a-regioisomer. The computational NBO charges around the carbon of the alkyne and at its a-position indicated that the polarization of alkyne was inductively mediated from the heteroatom. Thus, the alkyne polarization of the substituents in a-position of the alkynes can alone qualitatively predict the regiochemical outcome of the PKR. The results were published in Journal of Organic Chemistry,2014, 79, 10999-11010.
The second objective of the thesis was devoted to find synthetic applications of the adducts of the intermolecular PKR. The methodology was applied to the synthesis of natural products and phenanthrene derivatives.
The intermolecular PKR of internal alkynes proved to be the best method to synthesize the rac-sarkomycin methyl ester (anti-cancer drug). Thus, the fastest total synthesis of the rac-sarkomycin methyl ester was achieved in 2-pot reaction and 15 % overall yield and will be submitted to publication.
A new pathway was undertaken to obtain methyl jasmonate (frangance) from intermolecular PKR of unsymmetrical alkynes or terminal alkyne.
The first pathway used the PKR of unsymmetrical alkyne where our model to predict the regioselectivity was employed. It revealed that even the formed adduct gave the opposite isomer that we would expect, the computational NBO charges correlated well the experimental outcome.
The second pathway was carried out with the PKR of terminal alkyne. Our preliminary results allowed us to identify that the Claisen-Johnson rearrangement used as key step could be applied in the synthesis of the methyl jasmonate.
In the third objective, synthetic applications of intermolecular PKR of symmetrical alkynes toward photochemical transformations were undertaken from diaryl and heterocyclic alkynes.
The electrocyclisation reaction of the PKRs of disubstituted aryl alkynes could be optimised affording a new access to phenanthrene derivatives. This photochemical reaction induced the formation of two possible atropoisomers which by the steric hindrance of the PK adducts imposed by its substituents afforded a mixture of twisted isomers assimilated to helicene- like family. The PKR of bis(dimethyl phenyl) and bis(trimethyl phenyl) alkynes and norbornene were optimised affording excellent yields and times of reaction. The results were published in European Journal of Organic Chemistry, 2012, 30, 6058–6063. The reactivity of heterocyclic alkynes such as pyridyl and thiophenyl motifs regarding the PKR and photochemical reactions were studied. While the pyridyl motif did not afford the PK adduct, for the first time, PK adduct of the bis (dimethyl thiophenyl) alkyne successfully gave the reversible photoswitch reaction even the PKR gave low yield.La reacció de Pauson-Khand (PKR) descoberta durant l'any 1971 per P. L. Pauson i I. U. Khand, és formalment una cicloaddició [2+2+1] entre un alquè, un alquí i una molècula de monòxid de carboni típicament mediada o catalitzada per un complex de cobalt, generalment Co2(CO)8. En la PKR intermolecular quan falquí és terminal, la regioselectivitat és fàcil de determinar i només dóna un regioisòmer amb el substituent en a de l'adducte. Però, els resultats de la regioselectivitat son difícilment previsibles quan s'utilitzen alquins interns, i s'obtenen unes mescles de a i [3 regioisòmers en proporcions variables. El primer objectiu d'aquesta tesi va ser l'estudi de la regioselectivitat de la PKR intermolecular amb una varietat d' alquins interns amb substituents amb diferents propietats electròniques per un lloc i per altre lloc una cadena alifàtica. Es va establir una relació entre els canvis electrònics d'alquins asimètrics i els resultats de la regioselectivitat dels adductes de PKR de manera experimental i computacional. Els resultats van ser publicats al Journal of Organic Chemisty 2014, 79, 10999-11010. El segon objectiu de la tesi va ser la recerca d' aplicacions sintètiques dels adductes de la PKR intermolecular a la síntesi de productes naturals com l'èster metílic de la rac-sarcomicina (medicament contra el càncer) sintetitzat en només 4 passos i un rendiment global de 15%. Una nova via es va plantejar per obtenir l'èster metílic del jasmonat (fragància) mitjançant una reacció de PK intermolecular d'alquí terminal i una reacció de Claisen-Johnson que montren bons resultats preliminars. En el tercer objectiu, es van dur a terme aplicacions sintètics de la reacció de PK intermolecular d'alquins simètrics d'arílics i heterocíclics mitjançant transformacions fotoquímiques. Per primera vegada, el adducte PK del bis(dimetil tiofenil) alquí va donar amb èxit la reacció fotoreversible tot i que la PKR va donar baix rendiment. La reacció d'electrociclació dels adductes de PK d'alquins disubstuïts arílics es va poder optimitzada amb bons rendiments i temps de reacció donant un nou accés a derivats de fenantrens torçats quirals. Els resultats van ser publicats en l'European Journal of Organic Chemisty, 2012, 30, 6058-6063.
16
Meyer, Todd Roland. "Studies on selectivity in the Pauson-Khand reaction and synthesis of an intermediate of isocarbacyclin." Diss., Montana State University, 2005. http://etd.lib.montana.edu/etd/2005/meyer/MeyerT0805.pdf.
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Caldwell, John J. "Utilisation of organocobalt, organochromium and organophosphorus complexes in synthesis." Thesis, University of Strathclyde, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248753.
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Malcolm, Andrew G. "Applications of the Pauson-Khand reaction in the synthesis of tricyclic sesquiterpene natural products." Thesis, University of Strathclyde, 2016. http://digitool.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=27937.
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Within our laboratory, the syntheses of several related tricyclic sesquiterpene natural products have been completed, and, in all cases, the synthetic route employed the Pauson-Khand reaction (PKR) to generate the complex tricyclic core of each target. To further extend our studies within this area, we embarked upon synthesis of the[5,6,6]-fused tricyclic natural product α-duprezianene. Two main synthetic strategies towards construction of this complex and challenging target molecule have been investigated, and are described within. The first of these strategies focussed on direct formation of the central [5,6,6]-fused skeleton structure in a rapid and efficient fashion through the PKR. Initial synthetic endeavour thus focussed on the generation of suitable enyne intermediates to allow investigation of this key PKR. Towards this aim, a series of novel routes were proposed and investigated, ultimately delivering the requisite enyne intermediates. Regrettably, PKR of these enynes was unsuccessful and an alternative approach towards the target molecule was thus required. The second strategy towards formation of α-duprezianene involved initial construction of the related natural target sesquithuriferone. Indeed, formation of this target would provide a formal route to not only α-duprezianene, but also to a series of related sesquiterpene products. Once again, the PKR was employed in attempts to generate the [5,6,5]-fused tricyclic core of this target. In this regard, following investigation of several potential synthetic pathways, a robust and high yielding route was developed providing a formal total synthesis of sesquithuriferone. Key to this strategy was an extremely efficient PKR which furnished the [5,6,5]-skeletal core of sesquithuriferone in rapid fashion. In establishing this route, the original target α-duprezianene was also accessed in a formal manner. The success of this work serves to further reinforce the utility of the PKR within organic synthesis.
19
Merrill, James Malcolm. "Coordination Chemistry of Bis(diphenylphosphino)amine Ligands with Cobalt Carbonyl and the Intermolecular Catalyzed Pauson-Khand Reaction." Thesis, Virginia Tech, 2001. http://hdl.handle.net/10919/30874.
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Bis(diphenylphosphino)amine (PNP) ligands, prepared from (S)-(-)-1-methylbenzyl amine, (-)-cis-myrtanylamine, (S)-(-)-1,1-napthyl(ethyl)amine (PNP1 1a, PNP2 1b, and PNP3 1c respectively) and their cobalt carbonyl complexes are reported. In the absence of alkynes the PNP ligands chelate to the cobalt rather than bridging the two cobalt centers. Although the PNP ligands are chiral the crystal structures are best solved in centrosymmetric space groups with disorder at the chiral carbon with the exception of (PNP3)Co2(CO)6, 2c, which is solved in a non-centrosymmetric space group.
When the PNP ligand chelates to cobalt, as in 2, the compounds show activity for the catalytic Pauson-Khand reaction, whereas when the PNP ligand bridges, as in 3, the reaction precedes stiochiometrically. The use of these chiral ligands has not yet resulted in enantioselective catalytic Pauson-Khand cycloadditions. However, a small 15% e.e. was detected for the stiochiometric Pauson-Khand cycloaddition with 3c as the metal substrate.Master of Science
20
Gumrukcu, Yasemin. "Synthesis Of 2-heteroaryl Substituted Chiral Fused Cyclopenta[c]pyridine Derivatives Via Pauson-khand Reaction." Master's thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/12611176/index.pdf.
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The racemic homoallylic and homopropargylic alcohol derivatives were
resolved by applying chemoenzymatic method using various lipase type enzymes
i.e., PS-C II, Lipozyme, CAL-B. The enantiomeric excess values of the resultant
alcohols were determined by HPLC. These enantiomerically enriched homoallylic
and homopropargylic alcohols were subjected to N-propargylation and N-allylation,
respectively, by SN2 and modified Mitsunobu reactions. During the course of all
reactions, stereochemistry of the chiral centers were under controlling according to
the known reaction mechanisms. The resultant chiral N-tosylated enyne derivatives
afforded the corresponding chiral fused cyclopenta[c]pyridinone derivatives (69,
73, 75 and 77) with acceptable chemical yields and excellent diastereoslectivity
depending upon the conformational effect on the complete remote stereochemical
control for the newly generated chiral centers. The chemoenzymatic applications
done with biocatalysis (lipases) and the Pauson-Khand reaction are involved in
&ldquoGreen Chemistry&rdquo
approach.
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Pichon-Bouveret, Cecile. "Investigations on the carbon monoxide gas free Pauson-Khand reaction and mechanistic studies on cycloisomerisations." Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.520899.
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Bantreil, Xavier. "Alkylations allyliques intramoléculaires palladocatalysées : synthèse de lactames énantioenrichis et de nouveaux squelettes azatriquinanes." Paris 6, 2008. http://www.theses.fr/2008PA066391.
Full textAbstract:
Dans ce mémoire de thèse sont présentés le développement de réactions d’alkylations allyliques asymétriques intramoléculaires palladocatalysées, puis d’un enchaînement « alkylation allylique – Pauson-Khand ». A partir de précurseurs linéaires simples et aisément accessibles, des pyrrolidinones et des pipéridinones peuvent être synthétisées avec des rapports énantiomériques atteignant 94:6. Une étude approfondie montre que la formation de la liaison C-C serait l’étape énantiodiscriminante. Les complexes 3-allyliques intermédiaires de ces deux réactions ont été isolés et étudiés par RMN. L’utilisation d’un précurseur présentant un groupement électroattracteur encombrant permet d’effectuer une alkylation allylique intramoléculaire totalement diastéréosélective. Une réaction de Pauson-Khand permet ensuite d’obtenir des aza-triquinanes avec de bons rendements. Cet enchaînement a été appliqué à une approche de la synthèse d’un triquinane naturel, le cératopicanol.
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Bosson, Johann. "Synthèse de tétrahydrocyclopenta[c]acridines par réaction de Pauson-Khand : inhibition des kinases dépendantes des cyclines." Lyon 1, 2008. http://www.theses.fr/2008LYO10267.
Full textAbstract:
Dans le cadre du développement de nouvelles méthodologies de synthèse du squelette acridine, une voie de synthèse permettant un accès rapide au squelette tétrahydrocyclopenta[c]acridine est mise en place. L’étape clé de cette voie de synthèse est une réaction de Pauson-Khand intramoléculaire. Le mécanisme ainsi que la diastéréosélectivité cette réaction sont étudiés. Les kinases dépendantes des cyclines (CDK) possèdent un rôle de contrôle du cycle cellulaire. Dans la majorité des cas de cancer, ce processus de contrôle du cycle cellulaire est défaillant. L’implication des kinases dépendantes des cyclines dans les cas de cancer est étudiée et les inhibiteurs connus sont analysés. Certains composés issus de la famille des tétrahydrocyclopenta[c]acridines présentent une activité d’inhibition sélective des kinases dépendantes des cyclines dérégulées dans certains cas de cancer et ce, à des concentrations submicromolaires. De plus, le composé le plus actif de la série est co-cristallisé dans le site ATP du complexe CyclineA-CDK2. Ces résultats permettent l’établissement de relations Structure-Activité et aboutissent à la synthèse de composés de deuxième générationWhile developing a new acridine skeleton synthesis, a route allowing an efficient and fast synthesis of the tetrahydrocyclopenta[c]acridine core is developed. The key step of the synthesis is a Pauson- Khand Reaction. Several aspects (mechanism, diastereoselectivity) of the reaction are investigated. Some of the tetrahydrocyclopenta[c]acridines synthesized are exhibiting selective Cyclin Dependent Kinases inhibition activity in the submicromolaire range and this out of 70 other kinases. Those kinases are often deregulated in cases of cancer. The most active compound of the family has been crystallized in the ATP binding pocket of the CyclineA-CDK2 complex. Structure-activitiy relationships are established and second generation compounds are synthesized and evaluated
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Konya, Denes. "Contribution à l'étude de la réaction de Pauson-Khand : application à l'élaboration d'une version asymétrique catalytique." Université Joseph Fourier (Grenoble), 2003. http://www.theses.fr/2003GRE10010.
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Bernardes-Genisson, Vania. "Induction asymétrique dans la réaction intermoléculaire de Pauson-Khand et synthèse formelle de la (+)-brefeldine-A." Université Joseph Fourier (Grenoble ; 1971-2015), 1995. http://www.theses.fr/1995GRE10144.
Full textAbstract:
La réaction de Pauson-Khand, une cycloaddition entre un alcène, un alcyne et du monoxide de carbone représente l'une des méthodologies, mettant en jeu des métaux de transition, les plus efficaces pour préparer des cyclopentenones. L'emploi d'un auxiliaire de chiralite lie directement au partenaire acetylenique de cette réaction nous a permis, dans un premier temps, de développer une version asymétrique de la réaction intermoléculaire de pauson-khand. La réussite de cette stratégie a été possible grâce à la mise au point d'une méthode efficace et générale de préparation de complexes de cobalt d'ethers acétyléniques terminaux qui est basée sur l'utilisation d'un groupe silane comme élément protecteur de l'hydrogène acétylénique. Un travail initial d'évaluation des auxiliaires de chiralite, nous a permis d'élire le trans-deux-phenylcyclohexanol comme étant l'inducteur de choix dans notre cas. L'addition conjuguée hautement diastereoselective de réactifs organométalliques sur le cycloadduit enantiopur de Pauson-Khand, issu de la cyclisation avec le norbornadiene, nous a permis de développer une méthode de préparation enantioselective de cyclopentenones quatre-substituées, obtenues après réaction de retro diels-alder. Enfin, pour démontrer l'efficacité et l'importance de cette approche, nous avons réalisé une synthèse formelle enantioselective de la brefeldine-a naturelle, un macrolide intéressant pour ses activités immunodépressives
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Cabré, Montesinos Albert. "New Catalytic Methods for Pauson-Khand Reactions, Isomerization and Asymmetric Hydrogenations. Application to the Synthesis of Bioactive Compounds." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/668794.
Full textAbstract:
The main contribution of this doctoral thesis has been devoted to the field of synthetic organic chemistry. The Pauson-Khand reaction (PKR) is a metal-catalyzed [2+2+1] cycloaddition between an alkyne, an alkene and a carbon monoxide molecule. In this thesis, we have reported novel synthetic protocols to overcome some limitations. These protocols are based in the use of ethylene glycol as additive, which enhances the selectivities and yields of the corresponding PK adducts in stoichiometric manner, in both intramolecular and intermolecular fashion. Moreover, this positive effect was also observed in catalytic PKR and, furthermore the cobalt catalyst could be recycled by simple liquid-liquid separation when using toluene as reaction solvent. This strategy was then applied to the enantioselective total synthesis of (R)-Sarkomycin, which is an antitumoral agent.
Moreover, novel enantio- and regioselective isomerizations have been disclosed, focusing on allylic and heterocyclic compounds, using iridium catalysis or Lewis acids. First, Ir- MaxPHOX catalysts, which were designed by our research group, have been successfully employed in the unprecedented, enantioselective isomerization of allyl amides. On the other hand, commercially available and user-friendly Crabtree’s catalyst has been used for the regioselective isomerization of epoxides and N-sulfonyl aziridines. Finally, we have disclosed that B(C6F5)3, a Lewis acid, promotes the regioselective isomerization of 2,2-disubstituted oxetanes in extremely mild conditions. Moreover, and for all the selective isomerizations of heterocyclic compounds, DFT calculations have been performed to understand the reaction mechanism.
Finally, highly enantioselective and efficient catalytic methods to afford chiral β-methyl amines have been reported. Particularly, we have studied the asymmetric hydrogenation of N-protected allyl amines, which are a class of minimally functionalized olefins. For this enantioselective transformation, iridium catalysts bearing chiral phosphine-oxazoline ligands (UbaPHOX and MaxPHOX) have been used. As result, enantioenriched chiral amines were obtained in high enantiomeric excesses. To showcase the applicability of this methodology, we have reported the formal synthesis of Lorcaserin, which is an anorectic, among some other examples of bioactive compounds.La principal contribución de esta tesis doctoral se ha dedicado al campo de la química orgánica sintética. La reacción de Pauson-Khand (PKR) es una cicloadición catalizada por metales [2 + 2 + 1] entre un alquino, un alqueno y una molécula de monóxido de carbono. En esta tesis, hemos informado sobre nuevos protocolos sintéticos para superar algunas limitaciones. Estos protocolos se basan en el uso de etilenglicol como aditivo, que mejora las selectividades y rendimientos de los aductos PK correspondientes estequiométricamente, tanto intramolecularmente como intermolecularmente. Además, este efecto positivo también se observó en la PKR catalítica y, además, el catalizador de cobalto podría reciclarse mediante simple separación líquido-líquido cuando se usa tolueno como disolvente de reacción. Esta estrategia se aplicó luego a la síntesis enantioselectiva total de (R)-Sarkomicina, que es un agente antitumoral. Además, en esta tesis doctoral se han revelado nuevas isomerizaciones altamente regioselective, centrándose en compuestos alílicos y heterocíclicos, utilizando catálisis de iridio o ácidos de Lewis. Primero, los catalizadores Ir-MaxPHOX, que fueron diseñados por nuestro grupo de investigación, se han utilizado con éxito en la isomerización enantioselectiva sin precedentes de alilamidas. Por otro lado, el catalizador de Crabtree se ha utilizado para la isomerización regioselectiva de epóxidos y N-sulfonil aziridinas. Finalmente, hemos revelado que B(C6F5)3, un ácido de Lewis, promueve la isomerización regioselectiva de oxetanos 2,2-disustituidos en condiciones extremadamente suaves. Además, en todos estos procesos de isomerización de heterociclos se han realizado cálculos de DFT sobre el mecanismo de reacción. Finalmente, se han desvelado nuevos métodos catalíticos altamente enantioselectivos que proporcionan β-metilaminas quirales de forma eficiente. En particular, hemos estudiado la hidrogenación asimétrica de alilaminas N-protegidas, que son una clase de olefinas mínimamente funcionalizadas. Para esta transformación enantioselectiva, se han usado catalizadores de iridio que llevan ligandos quirales de fosfina-oxazolina (UbaPHOX y MaxPHOX). Como resultado, se obtuvieron aminas quirales con excesos enantioméricos elevados. Para mostrar la aplicabilidad de esta metodología, hemos presentado la síntesis formal de Lorcaserin, que es un anoréxico, entre otros ejemplos de compuestos bioactivos.
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Lledó, Ponsatí Agustí. "Aplicacions sintètiques dels adductes de Pauson-Khand del norbornadiè. Aproximació a la síntesi de prostaglandines i fitoprostans." Doctoral thesis, Universitat de Barcelona, 2006. http://hdl.handle.net/10803/2798.
Full textAbstract:
.En la present tesi doctoral s'han optimizat metodologies per a l'obtenció a escala preparativa d'adductes de Pauson-Khand (una cicloaddició [2+2+1] entre un alquí, un alquè i una molécula de CO) del norbornadiè i acetilens terminals, ja sigui en forma racèmica o enantiopura. Mitjançant una reacció de Pauson-Khand enantioselectiva emprant quantitats estequiomètriques d'un complex quiral de cobalt s'ha obtingut l'adducte del trimetilsililacetilè i el norbornadiè òpticament pur. Per obtenir el mateix adducte en forma racèmica s'han emprat protocols catalítics que simplifiquen la purificació dels productes i presenten una major economia atòmica. En aquestes condicions s'observa la formació del diastereoisòmer endo no desitjat en proporciones apreciables. La formació d'aquest producte és dependent de la pressió de CO emprada i es pot minimitzar dràsticament substituint un lligand CO por trifenilfosfina en el catalitzador de cobalt. De forma preliminar s'han assajat diversos auxiliars quirals en la reacció de Pauson-Khand catalítica y enantioselectiva sense haver arribat fins ara a bons excessos enantiomèrics. L'adducte de Pauson-Khand del norbornadiè i el trimetilsililacetilè (1) òpticament pur s'ha transformat en els desoxifitoprostans dPPJ1-I i II, confirmant així per primer cop la seva estereoquímica absoluta y relativa.
S'han estudiat les transformacions sintètiques sobre l'adducte de Pauson-Khand 1 racèmic, centrant-se en reaccions d'addició conjugada i desililació. En primer lloc s'han preparat les corresponents cetones beta-substituïdes amb diversos substituents alifàtics per addició conjugada de dialquilcuprats de liti o bé de reactius de Grignard en presència de quantitats catalítiques de Cu (I). Sobre aquests substrats s'ha desenvolupat una seqüència de metilenació/addició conjugada per introduir substituents en posició á al carbonil. Per addició conjugada de sintons d1 sobre l'adducte 1 s'han preparat 1,4-hidroxicetones i 1,4-oxoaldehids. Per fer-ho s'ha emprat l'anió cianur com a equivalent sintètic d'un aldehid i alternativament l'addició fotosensibilitzada de metanol per a la introducció directa d'un fragment hidroximetil.
Amb aquests intermedis sintètics s'ha abordat la síntesi de la prostaglandina A2. Per introduir la cadena omega de la PGA2 ens hem basat en reaccions de Wittig sobre els carboxaldehids mencionats. Alternativament s'ha introduït la cadena omega directament per addició conjugada d'un organometàl·lic funcionalizat sobre 1. Per elaborar la cadena á es va provar en primera instància l'alquilació en alfa al grup carbonil emprant halurs al·lílics com a electròfils. Vistos els baixos rendiments obtinguts per aquesta via es va aplicar la metodologia de metilenació/addició conjugada que va resultar més eficient. Els precursors així obtinguts es van sotmetre a condicions de retro-Diels-Alder per alliberar el fragment d'enona present en la PGA2. Si bé en compostos relacionats i compostos model més senzills la reacció és efectiva, no s'ha aconseguit reproduir-la en el cas de la PGA2. S'ha vist que el principal problema és l'eliminació inesperada del grup hidroxil protegit de l'alcohol al·lílic present en la cadena omega. Petites modificacions de la ruta sintètica ens permetrien en un futur pròxim arribar a la PGA2.
Per últim s'ha estudiat una reacció de transposició fotoinduïda dels adductes de Pauson-Khand del norbornadiè sense precedents en la literatura. Aquesta es va observar per primer cop en els assaigs d'addició fotosensibilitzada de metanol a 1. La reacció permet accedir a compostos amb una inusual estructura de triciclo[5.2.1.02,6]-3,8-decadien-10-ona partint d'adductes de Pauson-Khand derivats tant d'alquins terminals com interns i és compatible amb diversos grups funcionals com amines, èsters, alcohols i amides. La reacció te lloc tant en presència com en absència d'un sensibilitzador de triplets així com en presència d'un quencher de triplets, sempre amb velocitats aparents molt semblants tal com s'ha observat en seguir el curs de la reacció per espectroscòpia d'infraroig in situ. El mecanisme de la reacció, que transcorre per mitjà d'un intermedi diradicalari bisal·lílic, s'ha estudiat per mètodes computacionals ab inito.
"Synthetic applications of norbornadiene Pauson-Khand cycloadducts.Towards the synthesis of prostaglandins and phytoprostanes."
ABSTRACT IN ENGLISH.
The Pauson-Khand reaction is a [2+2+1] cycloaddition between an alkyne, an alkene and carbon monoxide mediated by a (typically) Co (0) complex to give a cyclopentenone. In this thesis we have optimized methodologies for the obtention of the adduct between norbornadiene and trimethylsilylacetylene (1) on a preparative scale both in enantiopure and racemic form. The optically pure compound (+)-1 has been employed in the total synthesis of deoxyphytoprostanes J1-I and J1-II (dPPJ1-I and II).
In order to obtain alpha, beta-disubstituted cyclopentenones from 1 a sequence of conjugate addition, desilylation, alpha-alkylation (or somehow related procedure) and retro-Diels-Alder reactions has been applied. First, simple organocopper reagents derived from commercial alkyl lithium and Grignard reagents were used to obtain a diverse set of addition compounds in good yields. Later on a d1 synthon addition to 1 was envisaged in order to obtain valuable intermediates for prostaglandin synthesis. The desired carboxaldehyde was obtained from reduction of a nitrile intermediate obtained from 1,4 addition of cyanide to 1. Alternatively a photoinduced addition of methanol to 1 was employed to obtain the related hydroxymethyl derivative. With the formyl and hydroxymethyl derivatives obtained we started the synthesis of prostaglandin A2 (PGA2). The ù chain was elaborated by Wittig reactions of these compounds or alternatively by conjugated addition of the appropriate functionalized organocopper reagent to 1. For the introduction of the alpha chain an enolate alkylation using allylic halides was used. The low yields thus obtained prompted us to develop an alternative sequence of methylenation and conjugate addition to the obtained exocyclic cyclopentenone which resulted in much better overall yields. The final retro-Diels-Alder step required to liberate the enone fragment resulted incompatible with the allylic moiety in the omega chain, a problem which we plan to overcome in the future.
In this thesis we also undisclosed a photochemical rearrangement of norbornadiene cycloadducts such as 1 which yields an unusual structure of tricyclo[5.2.1.02,6]-3,8-decadien-10- one and is tolerant to diverse functional groups. This unprecedented transformation was first encountered as a side reaction in the photoinduced methanol addition to 1, but could be converted in the main reaction in the absence of methanol.
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Finnegan, David Francis. "Tandem Reactions Involving Ruthenium Alkylidenes." Thesis, Boston College, 2009. http://hdl.handle.net/2345/728.
Full textAbstract:
Thesis advisor: Marc L. SnapperTandem Reactions have proven themselves to be useful reactions for the synthesis of highly complex materials. Ruthenium alkylidenes are shown to be useful precursors for the development of new tandem processes. First, a new tandem metathesis/hetero-Pauson-Khand process is developed using Grubbs' second generation catalyst. Next, various metatheis/olefin isomerization processes are explored
Thesis (PhD) — Boston College, 2009
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
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Laurent, Stéphane. "Alkylation des 4-alkylidènecyclopenténones issues de la réaction de Pauson-Khand alcyne/allène/CO : application à la synthèse de l'ester méhtylique de la (±)-[delta]12-PGA2." Lyon 1, 2005. http://www.theses.fr/2005LYO10018.
Full textAbstract:
La monoalkylation sélective des 4-alkylidènecyclopenténones (issues de la réaction de Pauson-Khand (PKR) alcyne/allène/CO) via leurs énolates fulvéniques de zinc a permis d'accéder à plusieurs cyclopenténones de type prostanoïde. De nouveaux assemblages spirocyclopenténones ont été préparés par bisalkylation intramoléculaire. La PKR d'alcools et éthers β-alléniques a fourni des cyclopenténones fonctionnalisées. Deux hydroxycyclopenténones, précurseurs potentiels de la [delta]12-PGA2, ont été obtenues. Deux synthèses de l'ester méthylique de la (±)-[delta]12-PGA2 envisagées à partir d'une 2-triméthylsilylcyclopenténone n'ont pu aboutir à cause de la difficulté à éliminer le groupement triméthylsilyle. L'alkylation directe de la 4-(3-hydroxyoctylidène)cyclopent-2-énone (stéréo-isomères E+Z) avec la chaîne α protégée des prostaglandines a conduit à l'ester méthylique de la (±)-[delta]12-PGA2. Une variation de la chaîne α a permis d'atteindre un analogue acétylénique
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Aiguabella, Font Nuria. "Reactivity and Applications of New Substrates for the Intermolecular Pauson-Khand Reaction: N-Boc-propargylamines and trifluoromethyl alkynes." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/131864.
Full textAbstract:
The Pauson-Khand reaction (PKR) is, formally, a [2+2+1] cycloaddition involving an alkene, an alkyne and a carbon monoxide molecule, typically mediated or catalyzed by a cobalt (0) complex. The product of this reaction is a cyclopentenone. This reaction, discovered in 1973 by P. L. Pauson and I. U. Khand constitutes, nowadays, one of the most prominent methods for the synthesis of five-membered ring compounds.
Regarding whether the alkene and the alkyne belong to the same molecule or are two different entities, we refer to the intra or intermolecular PKR, respectively. The intramolecular PKR has been the most extensively used one, since it allows the formation of complex polycyclic structures in very few synthetic steps and both the regio and stereoselectivity of the reaction are substrate-controlled. The intermolecular PKR has been traditionally less studied and exploited due to the limitations it presents. First of all, when the alkyne is internal and non-symmetrical the reaction may yield mixtures of regioisomers in different proportions depending on the electronic and steric properties of the substituents. If the reaction is carried out with a terminal alkyne, only one product is formed: the one that has the substituent alpha to the carbonyl in the final cyclopentenone. On the other hand, the reaction is very tolerant to different alkynes, but only tensioned and cyclic alkenes react satisfactorily, ethylene being an exception to this rule.
Cyclopentanic compounds are very abundant in nature, and they present a great variety of structures and functions. Probably, two of the most well-known families of cyclopentanic compounds in nature are prostaglandins and phytoprostanes. Prostaglandins are generated by the action of cyclooxygenase (COX) on the fatty acids that come from the phospholipid bilayer. The most common substrate for this reaction cascade in the human body is arachidonic acid. In plants, a similar process occurs with linolenic acid as substrate and the family of phytoprostanes as product. The extremely interesting properties of these compounds, such as antitumor activity, along with the difficulty to isolate them from natural sources, has led to an increasing interest on finding simple and efficient methods to access them. The fact that these products share a cyclopentenone ring (or a derivative) as a structural feature makes them aperfect synthetic target for the PKR. During the present thesis, we have developed a methodology to synthesize prostaglandins and phytoprostanes from the PK adduct of norbornadiene and N-Bocpropargylamine.
The synthesis of the aforementioned starting material can be carried out enantioselectively, so that the synthetic target can also be obtained as a single enantiomer. This methodology has been applied to the synthesis of a natural phytoprostane derivative: the methyl ester of 13-epi-12-oxo Phytodienoic acid.
The introduction of fluorinated substituents in organic molecules is extremely interesting, since the presence of these functional groups modifies the chemical and physical properties of the molecules to which they are incorporated. Given that, at the beginning of this thesis, there were no precedents of the intermolecular PKR of fluorinated alkynes, and considering that the particular stereoelectronic properties of these products could have an interesting impact on the regiochemical outcome of the PKR, we decided to study them in this work.
Our main conclusion has been that fluorinated substituents always occupy the alpha position to the carbonyl in the final cyclopentenone. This fact indicates that the steric bulk of fluorinated groups is larger than expected and overcomes its electronic properties (it is accepted that electron-donating groups prefer the alpha position in the final PK adduct, whereas electron-withdrawing groups prefer the beta position). Furthermore, in the case of trifluoromethyl alkynes, we have developed a methodology that allows to remove this group in order to obtain the previously unknown beta-substituted regiosiomers of PK adducts of terminal alkynes. We have also developed a methodology to carry out the synthesis of trifluoromethyl PK adducts enantioselectively. As an application of our methodology, we have developed a formal synthesis of alpha-cuparenone, a naturally occurring sesquiterpene.La reacción de Pauson-Khand (PKR) es, formalmente, una cicloadición [2+2+1] que transcurre entre un alqueno, un alquino y una molécula de monóxido de carbono. Como producto de esta reacción, típicamente mediada o catalizada por un complejo de cobalto (0), se genera una ciclopentenona. Los compuestos ciclopentánicos son muy abundantes en la naturaleza, y presentan gran variedad estructural y funcional. Probablemente, dos de las familias de compuestos ciclopentánicos más conocidas son la de las prostaglandinas y la de los fitoprostanos. En los últimos años se ha descubierto que algunos de estos productos (o derivados) poseen propiedades altamente interesantes (como, por ejemplo, actividad antitumoral). La dificultad de aislarlos de fuentes naturales ha despertado un gran interés por desarrollar métodos eficientes para obtenerlos sintéticamente. Dado que estos productos comparten un anillo de ciclopentenona como elemento estructural, constituyen unos substratos ideales para ser sintetizados mediante una PKR. Durante la presente tesis se ha desarrollado una metodología para sintetizar prostaglandinas y fitoprostanos a partir del aducto de PK del norbornadieno y la N-Bocpropargilamina. La síntesis de dicho producto de partida puede realizarse de manera enantioselectiva, de modo que el producto final puede obtenerse, asimismo, de modo ópticamente enriquecido. Esta metodología se ha ensayado con la síntesis del éster metílico de un fitoprostano natural: el ácido 13-epi-12-oxo fitodienóico. Por otro lado, al inicio de esta tesis, no se había realizado nunca una PKR intermolecular con alquinos fluorados y considerando que las particulares propiedades esteroelectrónicas de estos productos podían influir de un modo interesante en la regioquímica de la reacción, decidimos estudiarlos en profundidad durante esta tesis. La principal conclusión que se ha obtenido es que los substituyentes fluorados siempre ocupan la posición alfa al carbonilo en las ciclopentenonas finales. En el caso de que el substituyente fluorado sea un trifluorometilo, se ha desarrollado una metodología que permite quitarlo para obtener los hasta ahora desconocidos regioisómeros de aductos de PK de alquinos terminales. También se ha desarrollado una metodología para realizar dichas PKRs de forma asimétrica y obtener los aductos ópticamente puros. Como aplicación de esta estrategia, se ha realizado una síntesis formal de la alfa-cuparenona, un sesquiterpeno natural.
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Orgué, Gassol Sílvia. "Síntesi de nous lligands P-estereogènics. Aplicacions a la reacció de Pauson-Khand i a la hidrogenació asimètriques." Doctoral thesis, Universitat de Barcelona, 2015. http://hdl.handle.net/10803/300428.
Full textAbstract:
Els compostos de fòsfor han mostrat propietats úniques com a lligands per a la catàlisi asimètrica. El nostre grup de recerca ha estat dedicat a la síntesi de compostos P-estereogènics durant els darrers 5 anys. La present tesi doctoral ha estat dedicada al disseny i la síntesi de nous lligands P-estereogènics i a la seva aplicació en catàlisi asimètrica.
S’ha sintetitzat una nova família de difosfines amb quiralitat a l’àtom de fòsfor anomenades ThaxPHOS. Aquests lligands han estat complexats a cobalt i s’ha estudiat les propietats dels catalitzadors obtinguts per a la reacció de Pauson-Khand asimètrica i catalítica entre norbornadiè i alquins terminals. Com a resultat d’aquest estudi s’ha obtingut les enones corresponents amb resultats sense precedents fins al moment.
Seguidament s’ha desenvolupat una metodologia versàtil per a la síntesi de nous lligands P-estereogènics a partir d’aminofosfines òpticament pures. Mitjançant la hidròlisi àcida d’aminofosfines s’ha obtingut els àcids fosfinosos coresponents els quals han estat subjectes a la substitució nucleòfila a l’àtom de fòsfor. Mitjançant aquesta metodologia s’ha sintetitzat una nova família de lligands P-estereogènics.
Per tal de mostrar la utilitat de la nova metodologia desenvolupada s’ha sintetitzat una nova família de lligands fosfino-oxazolina, 5, els quals han estat emprats per a la hidrogenació asimètrica catalitzada per iridi. Els catalitzadors obtinguts han mostrat una elevada activitat per a aquest tipus de reacció, donant els productes hidrogenats amb elevada selectivitat en alguns casos.
Publicacions:
- S. Orgué, T. León, A. Riera, X. Verdaguer, Org. Lett. 2015, 17, 250–253.
- A. Flores-Gaspar, S. Orgué, A. Grabulosa, A. Riera, X. Verdaguer, Chem. Commun. 2015, 51, 1941–1944.Phosphorus compounds have demonstrated unique properties as ligands for asymmetric catalysis. Our group has been devoted to the synthesis of P-stereogenic ligands in the last 5 years. The present doctoral thesis is devoted to the design and synthesis of new P-stereogenic ligands and its application in asymmetric catalysis. We synthesized a new family of P-stereogenic diphosphines called ThaxPHOS. These ligands were complexed to cobalt and the resulting catalysts have been studied for the catalytic and asymmetric Pauson-Khand reaction between norbornadiene and different terminal alkynes. As a result of this study the corresponding enones were obtained with unprecedented results so far. Next, we have developed a versatile method for the synthesis of new P-stereogenic ligands from optically pure aminophosphines. The acidic hydrolisis of aminophosphines was performed giving rise to phosphinous acid boranes. This compounds were used as electrophiles for nucleophilic substitutions at the P centre. Using this methodology it was synthesized a new family of P estereogenic ligands. In order to show the usefulness of the new methodology developed, it was synthesized a new family of phosphine-oxazoline ligands, 5, which have been used for iridium catalysed asymmetric hydrogenation. The catalysts obtained showed high activity for this type of reaction, giving rise to the hydrogenated products with high selectivity in some cases. Publications ; - S. Orgué, T. León, A. Riera, X. Verdaguer, Org. Lett. 2015, 17, 250–253. - A. Flores-Gaspar, S. Orgué, A. Grabulosa, A. Riera, X. Verdaguer, Chem. Commun. 2015, 51, 1941–1944.
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Kintz, Nicolas. "Synthèse d'amines α-alléniques via les sels d'alcoxyphosphonium issus d'alcools α-alléniques : réaction de Pauson-Khand des alcools et amines α-alléniques." Lyon 1, 1998. http://www.theses.fr/1998LYO10090.
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Ce memoire de these decrit l'utilisation des alcools -alleniques dans deux types de reaction. Le premier concerne la reactivite de la fonction alcoolique qui peut etre substituee par un groupe amine par l'intermediaire d'un sel d'alcoxyphosphonium genere in situ. Le second a trait a la reactivite du diene cumule vis a vis des complexes alcynes-hexacarbonyledicobalt (reaction de type pauson-khand) ; celle-ci permet l'obtention de 4-(2-hydroxyalkylidene)cyclopent-2-enones. L'obtention des amines -alleniques a ete realisee par les methodes de mitsunobu et de tsunoda. Celles-ci necessitent l'emploi d'amines prealablement activees, destinees a augmenter l'acidite du proton aminique. De cette maniere des equivalents d'amines -alleniques secondaires ont ete produits. Nous avons egalement teste une methode recemment mise au point par fryen. Celle-ci ne necessite pas l'activation prealable de l'amine, et nous a permis de produire des amines -alleniques tertiaires. Une contrainte de cette derniere reaction est une faible chimioselectivite, car la production d'amines bis -alleniques concurrence parfois la production d'amines monoalleniques. La reaction de pauson-khand, induite par l'emploi d'oxyde de n-methylmorpholine, nous a permis d'acceder au squelette inedit des 4-(2-hydroxyalkylidene)cyclopent-2-enones a partir des alcools -alleniques. Cette cycloaddition (qui peut etre resumee en une cocyclisation formelle d'un allene, d'un acetylenique et de co) conduit a de bons rendements en produits de cyclisation de facon regiospecifique et avec une stereoselectivite toujours en faveur de l'isomere e. Quelques essais de cyclisation d'amines -alleniques nous ont conduit aux cyclopentenones correspondantes avec les memes caracteristiques reactionnelles.
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Morrison, Angus J. "Chiral and solid supported amine N-oxides as promoters in the Pauson-Khand reaction and the synthesis of α-methylene propellanone." Thesis, University of Strathclyde, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248255.
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Benedetti, Erica. "Cycloisomerization reactions catalyzed by transition metal complexes : synthesis of oxigen-and nitrogen-containing heterocyclic compounds." Paris 6, 2011. http://www.theses.fr/2011PA066448.
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Ces dernières années, le besoin de méthodes éco-compatibles pour la préparation d’une vaste gamme de produits chimiques requis par la société a poussé la recherche à développer de nouveaux procédés de synthèse qui soient plus efficaces et économiques. Afin de minimiser l'utilisation de matières premières et la production de déchets, une réaction chimique devrait procéder selon les principes d’économie d’atomes. Plus précisément, une séquence synthétique devrait idéalement avoir lieu avec un contrôle complet de la stéréochimie, de manière quantitative et sans formation de produits secondaires. Les réactions de cyclisation des systèmes polyinsaturés, catalysées par les métaux de transition, offrent une opportunité réelle d'atteindre les objectifs exposés ci-dessus. Dans cette thèse, quatre différentes classes de réactions de cyclisation, catalysées par les métaux de transition, ont été traitées: (1) les métathèses des dienes et des énynes, (2) les carbonylations de Pauson-Khand, (3) l’activation électrophile d'alcynes catalysée par l'iridium et (4) les cycloisomerizations d’allènes catalysées par l'or. Ces méthodologies, qui ont permis d'obtenir une haute complexité moléculaire en une seule étape de synthèse, ont été utilisées avec succès pour la formation de nombreux composés hétérocycliques oxygénés et azotés. Des études, qui décrivent la large applicabilité de ces réactions, sont publiées avec un rythme très rapide. Dans le futur, la découverte de nouvelles transformations catalysées par les métaux de transition continuera sûrement à occuper un rôle central dans la synthèse organique
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Tap, Aurélien. "Vers la synthèse totale de la Thapsigargine inhibiteur de l’enzyme SERCA." Thesis, Paris 5, 2013. http://www.theses.fr/2013PA05P619/document.
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La thapsigargine (Tg) est une lactone sesquiterpène polyoxygénée appartenant à la famille des guaianolides, isolée de Thapsia (Apiacae), une plante poussant communément dans le basin méditerranéen. Son intérêt dans le traitement du cancer de la prostate est basé sur son potentiel inhibiteur de l’enzyme endo/sarcoplasmique calcium ATPase (SERCA). Ce phénomène conduit à une augmentation de la concentration du calcium dans le lumen du réticulum endoplasmique et engendre une apoptose cellulaire. Dans un premier temps, un modèle 8-desoxy-bicyclo[5.3.0]decadiénone, de structure proche du squelette de la Tg, a été synthétisé par le biais d’une réaction clé de Pauson-Khand allène-yne catalysée par un complexe de rhodium. L’approche directe développée est robuste avec de hautes sélectivités et rendements. Cette voie a ensuite été appliquée à la synthèse du produit naturel. A partir d’un époxyde optiquement enrichi, la partie Sud de la Tg (le motif lactonique) est tout d’abord mise en place. Les centres C6 et C8 sont ensuite construits respectivement par alcynylation/réduction asymétrique et par propargylation énantiosélective. Cette première approche a permis d’isoler un produit énantiopure possédant les centres chiraux C6, C7 et C8 ainsi que du motif lactonique en dix-sept étapes. Une seconde voie a été initiée permettant la mise en place plus rapide de la partie Sud de la molécule incluant les centres asymétriques C6, C7, C8 et C11 par le biais d’une réaction de dihydroxylation. Cette seconde voie a permis d’isoler un produit racémique possédant les centres chiraux C6, C7, C8 et C11 ainsi que du motif lactonique en dix étapes. Parallèlement, une étude méthodologique a été menée sur la réaction de Pauson-Khand allénol-yne intramoléculaire. Treize composés bicycliques ont été synthétisés en série acétal et NTsThapsigargin (Tg) is a highly oxygenated sesquiterpene lactone belonging to the guaianolide family, isolated from the Mediterranean plant species Thapsia (Apiaceae). Its interest towards treatment of prostate cancer is based on the potency of this compound as an inhibitor of the endo/sarcoplasmic calcium ATPase (SERCA) inducing an increase in cytosolic calcium concentration and leading to apoptotic cell death. A straightforward approach to a highly functionalized 8-desoxy-bicyclo[5.3.0]decadienone model close to the Tg framework has been achieved through a key Rh(I) allenic Pauson-Khand reaction (APKR). The synthetic route developed therein is robust and the yields and selectivities are high. This approach was used in the synthesis of the natural compound. Starting from the same chiral epoxide, the bottom portion of the Tg (lactone core) is first built, then C6 and C8 carbons are functionalized respectively by asymmetric reduction and enantioselective propargylation. This first way allowed to synthesize a seventeen steps-enantiopure product with C6, C7, C8 chiral centers and the lactone core. A second way is performed to set up faster the bottom part of the molecule included C6, C7, C8 and C11 asymmetric centers through a dihydroxylation step. This second approach allowed to synthesize a ten steps-racemic product with C6, C7, C8, C11 chiral centers and the lactone core. Meanwhile, a methodological study was conducted on the intramolecular allenol-yne Pauson-Khand reaction. Thirteen bicyclic compounds were synthesized in acetal and NTs series
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Gates, Richard J. "Dynamics of the Solvent Exchange Reaction of Weakly Bound Organic Solvents to Group 6 Transition Metal Carbonyls and the Molybdenum Hexacarbonyl Mediated Pauson-Khand Reaction." BYU ScholarsArchive, 2012. https://scholarsarchive.byu.edu/etd/2936.
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Many organometallic reactions are solvent-dependent, suggesting solvent molecules interact with reaction intermediates. Studies of the solvent exchange reaction of group 6 transition metal carbonyls with moderately binding ligands have provided insight into these interactions, however, studies of the mechanism for this reaction with weakly binding ligands have not been performed. Experiments were conducted on the nanosecond time scale in methylcyclohexane over the temperature range of 4 to 44 °C using Step Scan FTIR (SS FTIR) spectroscopy with weakly binding ligands benzene and mesitylene. Upon photolysis of the metal hexacarbonyls, the kinetically favored product (M(CO)5(solv)), decays following pseudo-first-order kinetics to the thermodynamical favored product, M(CO)5(L). The decay is fit using a single exponential decay with a single exponential instrument response function, time zero and an offset. An Arrhenius plot yielded activation energies of 23.7 kJ/mol (M = Mo, L = benzene), 35.1 kJ/mol (M = W, L = benzene) and 29.8 kJ/mol (M = Mo, L = mesitylene). DFT calculations using NWCHEM gave binding energies of 45.8 and 54.3 kJ mol-1 for Mo(CO)5C6H12 and W(CO)5C6H12. The experimental and computational results suggest the exchange mechanism proceeds through an associative pathway, were slightly negative values of the entropy of reaction denote that the transition state has greater metal solvent bond breaking character then the more moderately binding ligands in the literature. Density Functional theory was used to calculate C-O vibrational frequencies of metal carbonyl complexes measured in our work and other complexes from the literature, with density functionals B3LYP, M06 and M06-L. Measured and computational frequencies were compared to obtain both an overall vibrational shift and a scaling factor. Scaling factors were found to be 0.9519±0.0095 for B3LYP, 0.9429 ± 0.0087 for M06 and 0.9565 ± 0.0095 for M06-L with overall shifts of 102 ± 16, 121 ± 15, 93 ± 17 cm-1, respectively. The molybdenum mediated Pauson-Khand reaction, a [2+2+1] cyclo-addition begins very similarly to the solvent exchange reaction on molybdenum. The initial product, the solvated complex, decays away with pseudo-first-order kinetics as the solvent is replaced by the C-C triple bond in 2-(2-propen-1-yl)-2-(2-propyn-1-yl)-,1,3-diethyl ester. An Arrhenius plot over the temperature range of -8 to 20° C yielded an energy of activation of 15.6 kJ/mol.
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Mariaule, Gaëlle. "Accès original aux hétérocycles par la catalyse organométallique : développement de nouveaux inhibiteurs de kinases." Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05P612/document.
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Cette thèse est composée de deux parties distinctes ayant comme thématique commune, la synthèse d’hétérocycles via la catalyse organométallique.Nous nous sommes intéressés, dans un premier temps, à une voie de synthèse permettant un accès rapide au squelette tétrahydrocyclopenta[c]acridine. Ces composés polyfonctionnalisés sont obtenus très efficacement en seulement trois étapes dans des conditions particulièrement douces. L’étape clé de cette synthèse est une réaction de Pauson-Khand intramoléculaire catalysée au cobalt. Certains composés issus de la famille des tétrahydrocyclopenta[c]acridines présentent une activité d’inhibition sélective envers les kinases dépendantes des cyclines (CDKs), et plus particulièrement la CDK2. Un composé chef de file est identifié, puis grâce aux données de co-Cristallisation avec CDK2 et de modélisation moléculaire, suivi de l’étude des relations structure-Activité, la conception rationnelle d’une deuxième génération de molécules est rendue possible. Le composé le plus avancé présente une CI50 de 300 nM envers CDK2/cyclin A et un excellent profil de stabilité métabolique.Dans un deuxième temps, nous avons étudié et développé une réaction tandem d’addition/cyclisation catalysée par l’argent, avec des nucléophiles carbonés sur des substrats ortho-Alcynylbenzaldéhydes. La stratégie de synthèse conduit à des dérivés 1H-Isochromènes par création de deux nouvelles liaisons (C-C et C-O). Une étude approfondie de la réaction tandem nous a permis d’obtenir une large gamme de dérivés d’isochromènes en mettant en évidence l’influence de différents substituants, portés par le groupement alcyne ou le substrat, ainsi que l’utilisation de différents nucléophiles carbonés (alcynes, aromatiques, hétéroaromatiques). Les limitations de la réaction tandem ont également pu être identifiéesMy thesis proJect is organized around two main topics having in common organometallic chemistry and the synthesis of heterocycles.Firstly, we were interested in a methodology for the synthesis of tetrahydrocyclopenta[c]acridines. These compounds are synthesized in three steps from various quinolines. The key step is a cobalt-Catalyzed intramolecular Pauson-Khand reaction. Some compounds of this family exhibit selective Cyclin Dependent Kinases (CDKs) inhibition, particulary against CDK2, in the submicromolar range. A hit compound has been identified, and then using data from co-Crystallization with CDK2 and molecular modeling, followed by the study of structure-Activity relationships, the rational design of a second generation of molecules has been investigated. The most advanced compound has an IC50 of 300 nM against CDK2/cyclin A with an excellent metabolic profile. In the second axis of research, we have studied and developed a new silver-Catalyzed tandem addition/cyclization reaction with carbon nucleophiles. The systems studied are (hetero)aromatics compounds having an aldehyde group and in ortho-Position an alkynyl group. The synthetic strategy leads to 1H-Isochromene derivatives by creating two new bonds. A thorough study of the tandem reaction allowed us to obtain a wide range of isochromene derivatives, highlighting the influence of different substituents carried by the alkyne group or on the (hetero)aromatic substrates; and also to investigate the use of different carbon nucleophiles (alkynes, aromatics and heteroaromatics). The limitations of the tandem reaction have also been identified
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León, Serrano Thierry. "Síntesi estereoselectiva de fosfines amb quiralitat al fòsfor. Aplicacions en catàlisis." Doctoral thesis, Universitat de Barcelona, 2012. http://hdl.handle.net/10803/53534.
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L’obtenció de lligands quirals eficients i de fàcil accés segueix essent un dels objectius principals en catàlisi. Les fosfines estereogèniques voluminoses han mostrat ser molt eficients en un ampli ventall de reaccions catalítiques. No obstant, la seva síntesis de forma enantiomèricament pura és molt sovint complicada. Podem considerar que els mètodes més efectius per a la construcció de fòsfor estereogènic són els desenvolupats per Jugé i Evans basats en l’obertura d’oxazafosfolidines enantiopures i la desprotonació enantioselectiva de fosfino-borans, respectivament. Aquests mètodes, tanmateix, presenten limitacions i desavantatges. Aquest fet confereix atractiu al desenvolupament de nous processos per a la síntesi de fòsfor estereogènic. En la present tesi doctoral, es va estudiar la condensació de fenil i tert-butilfosfines amb el (cis)-1-amino-2-indanol. Aquestes ens conduí a les corresponents oxazafosfolidines amb bon rendiment i diastereoselectivitats de fins a 18 : 1. La condensació amb aquest aminoalcohol ens proporcionà oxazafosfolidines amb funció NH lliure. Justament aquesta nova funcionalitat s’ha revelat clau en la química d’obertura d’anells d’oxazafosfolidines. Pel que fa l’obertura d’anell de la 2-feniloxazafosfolidina amb organolítics, aquestes transcorregueren amb inversió o retenció depenent de la substitució sobre l’àtom de nitrogen. Quan tenim un grup NH, l’obertura transcorre amb inversió mentre que quan el nitrogen està substituït amb un metil s’observa retenció tal i com havia descrit Jugé i col•laboradors. En la mateixa línia, l’obertura d’anell de la 2-tert-butiloxazafosfolidina amb el grup NH lliure amb organomagnesians té lloc de forma totalment estereoselectiva a temperatures elevades amb inversió. També s’ha desenvolupat una obertura reductiva de la 2-tert-butiloxazafosfolidina mitjançant l’ús combinat d’una font d’hidrur i un magnesià. Aquesta obertura també és totalment estereoselectiva i no té precedents en la literatura. Els productes d’obertura de la 2-feniloxazafosfolidina es van hidrolitzar segons la metòdica descrita per Jugé a les corresponents metoxifosfines amb bons rendiments i elevats ee. Els productes d’obertura de la 2-tert-butiloxazafosfolidina amb grups alquil es van poder trencar de l’auxiliar quiral amb Li/NH3(liq.) obtenint-se les aminofosfines amb ee>99%. Alternativament, es va desenvolupar una seqüència d’eliminació i posterior hidròlisis que permet alliberar les aril-tert-butilaminofosfines amb bons rendiments i ee>99%. Aquests es va derivatitzar la tert-butilaminofosfina en diferents compostos. Finalment també es va descriure una nova família de lligands basats en fosfinosulfonamides. Es van descriure nous complexos de Rh-fosfinosulfonamida els quals es van aplicar a la reacció de cicloaddició [2+2+2] intramolecular de manera exitosa. Aquests complexos ens van permetre superar amb escreix els resultats descrits prèviament. Finalment, es va dissenyar una nova família de lligands que hem anomenat ThaxPHOS. Es van emprar aquests en la reacció de Pauson-Khand intermolecular catalítica enantioselectiva. La desprotecció i complexació amb dicobalt dóna molt bon resultats i bones diastereoselectivitats gràcies a equilibracions tèrmiques. Inicialment, es va dissenyar una estratègia estequiomètrica enantioselectiva per a l’obtenció de l’adducte de Pauson-Khand amb acetilè lliure sense emprar l’acetilè en forma de gas. L’aplicació d’aquests complexos en la reacció catalítica han donat els millors resultats mai descrits en aquest camp. S’ha plantejat un nou mecanisme catalític per justificar els resultats obtinguts.The synthesis of efficient and easily affordable chiral ligands are one of the main goals in catalysis. Bulky stereogenic phosphine have demonstrated to be excellent ligands in a broad range of catalytic reactions. Furthermore, their synthesis in an optically pure form is usually difficult. We can consider that the method developed independently by Jugé and Evans are the most effective in this field. Nevertheless, these methods have some drawbacks. These downsides need to be improved and new synthetic methodologies need to be developed to obtain stereogenic phosphorus compounds. In this doctoral thesis we studied the condensation of phenyl- and tert-butylphosphines with (cis)-1-amino-2-indanol. These allowed us to obtain the corresponding oxazaphospholidines with excellent yields and diastereoselectivities (up to 18 : 1). These condensations allowed us to get a free NH functionality. We saw as this secondary amine was the key for our ring-opening strategy. Taking advantage of this group, we performed the ring-opening reaction allowing us to obtain the corresponding ring-opened product with inversion of configuration on the phosphorus atom. This reaction was carried out with total diastereoselectivity, and the ring-opened products obtained from 2-phenyloxazaphospholidine were hydrolyzed following the Jugé procedure described in literature. We obtained the corresponding methoxyphosphine with excellent yields and high ee. The ring-opened products obtained from 2-tert-butyloxazaphospholidine with alkyl groups were reductively cleaved with Li/NH3(l) affording the corresponding aminophosphine with ee>99%. Alternatively, we developed a new strategy based on elimination-hydrolysis to free the corresponding aryl-tert-butylaminophosphines with excellent results and optically pure. Subsequently, we described a new ligand family based on phosphinosulfonamide. We described new complexes of Rh-phosphinosulfonamide and we tested them in the intramolecular cycloaddition [2+2+2] significantly improving on the previous results described. Finally, we designed a new family of PnP* ligands called ThaxPHOS. These ligands were used in the enantioselective catalytic intermolecular Pauson-Khand reaction. The deprotection and successive coordination gave excellent yields and diastereoselectivities due to thermal equilibration. We used ThaxPHOS ligands in this reaction and we described the best results ever obtained in this field and we described a new catalytic mechanism to explain our results.
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Rosol, Malgorzata. "Síntesis y estudio de nuevos derivados ciclometalados del ferroceno / Synthesis and study of new cyclometallated derivatives of ferrocene." Doctoral thesis, Universitat de Barcelona, 2007. http://hdl.handle.net/10803/2799.
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The present Doctoral Thesis focuses in two main fields: alkyne-dicobaltcarbonyl complexes (PART I) and chiral ferrocene derivatives (PART II). Therefore, the obtained results can be summarized as follow: 1. The methodology designed for the synthesis of enantiomerically pure phosphane-substituted carbonyl complexes of propargyl aldehyde was not successful. The steric hindrance at position C-4 of the oxazolidin-2-one and oxazolidin-2-thione appears to difficult the removal of the auxiliary in the corresponding N-(2-alkynoyl) dicobaltcarbonyl complexes.
2. The general catalytic behavior of octacarbonyl dicobalt in the opening of cyclic ethers, such as tetrahydrofuran, by acid chlorides, leading to 4-chlorobutyl esters, has been demonstrated.
3. A pathway to access 1'-substituted and 2-substituted beta-ferrocenyl beta-amino alcohols has been developed. In this way, the synthesis with a high level of enantiomeric purity of (S)-2-amino-2-(1'-methyl)ferrocenylethanol, (pS,R)-2-amino-2-(1-trimethylsilyl)-ferrocenyl ethanol and (pR,R)-2-amino-2-(1-methyl) ferrocenyl ethanol has been achieved via their corresponding diols.
4. A general methodology which gives easy access to mono and disubstituted (1,1'- and 1,2-) 4-ferrocenyl-1,3-oxazolines has been developed.
5. A new type of interannular cyclopalladation of ferrocene has been established. The reaction seems to be quite general for 4-ferrocenyl-1,3-oxazolines with different degrees of substitution of the ferrocene moiety, provided that the C2-oxazoline substituent bears no á-hydrogens. The reaction of 4-ferrocenyl-1,3-oxazolines with palladium acetate in benzene leads to the formation of C2-symmetric complexes with two ferrocene moieties cycloplalladated at the 1' position, connected by a central palladium and four acetate bridges. When the cyclopalladation is performed by disodium tetrachloropalladate, a similar complex, but with two chloride bridges, is obtained. The 3-palladium acetate complexes can be converted into the 2-palladium chloride ones by treatment with lithium chloride in methanol. The structures of both types of complexes have been thoroughly studied by spectroscopy and by X-ray diffraction.
6. Cyclic voltammetric studies of these novel interannular palladacycles have been performed.
7. The µ-chloro bridged dipalladium complex (S)-84 undergoes bridge-splitting with triphenylphosphine leading in nearly quantitative yield to the monomer complex (S)-95. On the other hand, the reaction of (S)-84 with iodine affords 1'-iodo-2-tert-butyl-4-ferrocenyl oxazoline (S)-100. This compound has been converted into 1'-phenyl-2-tert-butyl-4-ferrocenyloxazoline (S)-101 by Suzuki coupling with phenylboronic acid. Finally, (S)-84 leads in good yields to the 1'-diphenylphosphinyl- and 1'-diphenylphosphinothioyl ferrocenes (S)-103 and (S)-104.
8. Interannularly palladated 4-ferrocenyl-1,3-oxazolines behave as active promoters of the Heck olefination, allowing the reaction to be performed at lower temperatures than previously known CN-palladacycle pre-catalysts derived from ferrocene. In the reaction medium, the olefin partner couples with the 1'-position of the ferrocene, leading to the formation of soluble palladium(0) catalytic species. For the first time, the ligand-olefin adduct has been isolated and unequivocally characterized, and further evidence favoring the involvement of a Pd(0)/Pd(II) catalytic cycle has been obtained.
9. The new interannular cyclopalladated ferrocenes have been found to be good catalysts for the asymmetric aza-Claisen rearrangement. Thus, the rearrangement of (E)-cinnamyl N-aryl benzimidates 129-131 takes place with moderate yields (40-49%) and with excellent enantioselectivity (up to 90% ee of the rearranged amide 138). Interestingly enough, the acetate-bridged 3Pd complexes lead to the (S) enantiomer of the rearranged allylic amide, while the chloride bridged 2Pd complexes (from the same (S)-enantiomer of the chiral 4-ferrocenyl-1,3-oxazoline) lead to the opposite (R) enantiomer of the amide.
10. New and outstanding catalysts for the aza-Claisen rearrangement of (E)- and (Z)-allylic trichloroacetimidates have been found. The rearrangement of both (E)- and (Z)-hexenyl trichloroacetimidates, performed in chloroform solution at 38oC with a molar 5% of the chloride bridged 1'-cyclopalladated complex, takes place with quantitative conversion and with outstanding enantioselectivity (>98% ee), according to 1H-NMR and HPLC analyses. Intriguingly, both diastereomers of the starting imidate lead to the same enantiomer (S) of the rearranged amide 142.
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Biletskyi, Bohdan. "Développement de nouvelles transformations catalysées au cobalt." Electronic Thesis or Diss., Aix-Marseille, 2018. http://theses.univ-amu.fr.lama.univ-amu.fr/181207_BILETSKYI_50nlz932ipxkk485izc94s_TH.pdf.
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L'utilisation du cobalt en synthèse et catalyse organiques est reconnue depuis les années 1970, notamment dans la réaction de Pauson-Khand. Dès lors, de nombreux systèmes catalytiques au cobalt ont prouvé leur efficacité dans diverses transformations chimiques telles que les cycloadditions [2+2+2] ou l'activation des liaisons C(sp2)-H. Dans ce manuscrit, sont présentés des transformations chimiques basées sur l’utilisation de catalyseurs au cobalt s’effectuant essentiellement avec économie d’atomes, et les essais de développement des versions énantioselectives.Tout d'abord, l'activité de catalyseurs au cobalt(I) a été établie dans la réaction de cycloisomérisation de diènynes pour obtention de bicycles[4.3.0]. Les études concernant différents paramètres du système catalytique ainsi que le champ d'application sont présentés. Les catalyseurs à base d'acétate de cobalt(II) se sont révélés très efficaces pour les réactions d'hydroalcynylation. L'hydroalcynylation de vinylaziridines a été développée après optimisation du système catalytique et, le domaine d’application selon la nature des réactants a été défini. Finalement, les études préliminaires de l'allylation énantiosélective avec les catalyseurs de cobalt(II) ont été réalisées. Ceux-ci se sont révélés plutôt comme activateurs du groupement carbonyle, compromettant la version asymétrique de la réactionThe application of cobalt in organic synthesis and catalysis has been known since the 1970s, especially in Pauson-Khand reaction. Until now, a lot of catalytic systems with cobalt have demonstrated their efficiency in various chemical transformations including [2+2+2] cycloadditions or the activation of C(sp2)-H bonds. In this manuscript are presented the chemical transformations based on the use of cobalt to catalyze atom-economical reactions, and the attempts to develop enantioselective versions. First of all, the activity of cobalt(I) catalysts was established for the cycloisomerisation reaction of dienynes giving bicycles[4.3.0]. The studies of different parameters of the catalytic system, as well as the scope reaction, will be presented. Moreover, the catalysts based on cobalt(II) acetate proved to be very efficient for hydroalkynylation reactions. The hydroalkynylation reaction of vinylaziridines was developed after catalyst optimisation and, the scope reaction according to the nature of reactants was defined. Finally, preliminary studies of enantioselective allylation using cobalt(II) catalysts were performed. These promoters were found to be activators of the carbonyl group, thus compromising the asymmetric version of the reaction
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Biletskyi, Bohdan. "Développement de nouvelles transformations catalysées au cobalt." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0668/document.
Full textAbstract:
L'utilisation du cobalt en synthèse et catalyse organiques est reconnue depuis les années 1970, notamment dans la réaction de Pauson-Khand. Dès lors, de nombreux systèmes catalytiques au cobalt ont prouvé leur efficacité dans diverses transformations chimiques telles que les cycloadditions [2+2+2] ou l'activation des liaisons C(sp2)-H. Dans ce manuscrit, sont présentés des transformations chimiques basées sur l’utilisation de catalyseurs au cobalt s’effectuant essentiellement avec économie d’atomes, et les essais de développement des versions énantioselectives.Tout d'abord, l'activité de catalyseurs au cobalt(I) a été établie dans la réaction de cycloisomérisation de diènynes pour obtention de bicycles[4.3.0]. Les études concernant différents paramètres du système catalytique ainsi que le champ d'application sont présentés. Les catalyseurs à base d'acétate de cobalt(II) se sont révélés très efficaces pour les réactions d'hydroalcynylation. L'hydroalcynylation de vinylaziridines a été développée après optimisation du système catalytique et, le domaine d’application selon la nature des réactants a été défini. Finalement, les études préliminaires de l'allylation énantiosélective avec les catalyseurs de cobalt(II) ont été réalisées. Ceux-ci se sont révélés plutôt comme activateurs du groupement carbonyle, compromettant la version asymétrique de la réactionThe application of cobalt in organic synthesis and catalysis has been known since the 1970s, especially in Pauson-Khand reaction. Until now, a lot of catalytic systems with cobalt have demonstrated their efficiency in various chemical transformations including [2+2+2] cycloadditions or the activation of C(sp2)-H bonds. In this manuscript are presented the chemical transformations based on the use of cobalt to catalyze atom-economical reactions, and the attempts to develop enantioselective versions. First of all, the activity of cobalt(I) catalysts was established for the cycloisomerisation reaction of dienynes giving bicycles[4.3.0]. The studies of different parameters of the catalytic system, as well as the scope reaction, will be presented. Moreover, the catalysts based on cobalt(II) acetate proved to be very efficient for hydroalkynylation reactions. The hydroalkynylation reaction of vinylaziridines was developed after catalyst optimisation and, the scope reaction according to the nature of reactants was defined. Finally, preliminary studies of enantioselective allylation using cobalt(II) catalysts were performed. These promoters were found to be activators of the carbonyl group, thus compromising the asymmetric version of the reaction
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Yen, Po-Jen, and 顏伯任. "Sequential asymmetric oganocatalytic anti-selective Michael reaction－Reduction－Lactonization－Pauson-Khand reaction." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/02527947231986221379.
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碩士國立中正大學
化學暨生物化學研究所
100
A steroselectivity synthesis of fully subsititude decahydro-1H- pentaleno [2,1-c]pyran derivatives have been achieved with alkylidene malonates and aldehydes. By a sequential oganocatalyzed anti-selective Michael reaction－reduction－lactonization－Pauson-Khand reaction, varios additives effected different results of steroselectivity.
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Olson, Julie Ann. "Development of a tandem Diels-Alder/Pauson-Khand strategy for synthesis of tetracycles." 2010. http://hdl.handle.net/10090/15180.
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Wells, Charles Eugene. "An approach towards the synthesis of Nakadomarin A and Manzamine A Using Pauson-Khand technology." Thesis, 2004. http://hdl.handle.net/2152/29857.
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This dissertation is devoted to our synthetic studies towards the total synthesis of the natural product Nakadomarin A, and Manzamine A using the Pauson-Khand reaction as the key step. Chapter 1 reviews past work using Pauson-Khand technology. Chapter 2 reviews the N-alkyl piperidine family of natural products. Chapter 3 reviews published total syntheses of Manzamine A and Nakadomarin A. Chapter 4 explores our work using the Pauson-Khand reaction to form the ABC rings of Nakadomarin A and subsequent B ring expansion to form the ABC ring core of Manzamine A. Chapter 5 explores our approaches to the furan portion, as well as, our approaches to the macrocyclic F ring. Finally Chapter 6 contains the description of the experiments performed along with relevant analytical data.text
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Gößmann, Matthias [Verfasser]. "N-funktionalisierte 1-Alkinylamide in inter- und intramolekularen Pauson-Khand-Reaktionen / vorgelegt von Matthias Gößmann." 2000. http://d-nb.info/958909326/34.
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Lanver, Andreas. "Studien zur übergangsmetallvermittelten Synthese von bioaktiven carbocyclischen Nucleosiden und von Rotenoiden /." 2006. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=017062177&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
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Günter, Markus [Verfasser]. "Asymmetrische Synthese von bicyclischen α-Aminosäuren [Alpha-Aminosäuren] durch intramolekulare Pauson-Khand-Reaktion von 1-Alkenylsulfoximinen und Festphasensynthese mit Allylsulfoximinen. / vorgelegt von Markus Günter." 2003. http://d-nb.info/971495645/34.
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Shanahan, Charles S. "Efforts towards the total synthesis of the stemofoline alkaloids utilizing a novel 1,3-dipolar cycloaddition reaction and application of the Pauson-Khand reaction as a novel entry into bridged azabicyclic ring systems." Thesis, 2011. http://hdl.handle.net/2152/ETD-UT-2011-08-4101.
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A novel application of the Pauson-Khand reaction was applied to the synthesis of a series of bridged azatricyclic piperazines. This method represents the first application of the Pauson-Khand reaction to synthesize azabridged scaffolds. The ubiquity of bridged azabicyclic ring systems in biologically active natural product skeletons has provided the synthetic chemist with a wealth of opportunity for development over the last century. To this day, the development of new methodologies to tackle these structurally challenging systems remains at the forefront of synthetic chemistry.
During our efforts to achieve a total synthesis of the stemofoline alkaloids, we have thus far developed a novel and scalable synthetic strategy to access the fully functionalized caged azatricyclic core of these challenging alkaloids. The overall synthetic strategy we have implemented began with the commercially available and affordable 2-deoxy-D-ribose as a chiral starting material. Furthermore, we have developed a novel 1,3-dipole cascade cycloaddition, which was successfully employed as the key step in the construction of the bridged azatricyclic core of the stemofoline alkaloids.text
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Miller, Kenneth Aaron 1979. "(Rh(CO)₂Cl)₂-catalyzed allylic substitution reactions and domino sequences and application of the Pauson-Khand reaction to the synthesis of azabicyclic structures: total synthesis of (-)-alstonerine." Thesis, 2007. http://hdl.handle.net/2152/3495.
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Examination of the scope of the [Rh(CO)₂Cl]₂-catalyzed allylic substitution reaction as well as the development of a domino [Rh(CO)₂Cl]₂-catalyzed allylic alkylation/Pauson Khand reaction is described. A number of experiments were carried out in order to explore the novel regioselectivity in the [Rh(CO)₂Cl]₂-catalyzed allylic substitution reaction, and the [Rh(CO)₂Cl]₂-catalyzed allylic substitution reaction was found to give products resulting from attack of the nucleophile on the carbon bearing the leaving group in a highly regioselective fashion in most cases. Examination of allylic carbonate substrates containing similar substitution at each allylic site was carried out, and conditions that minimize equilibration of active intermediates were determined. Intramolecular [Rh(CO)₂Cl]₂-catalyzed allylic alkylation was accomplished to synthesize challenging eight-membered lactone ring systems. Nucleophile scope was explored with regards to the [Rh(CO)₂Cl]₂-catalyzed allylic substitution reaction, and malonates, substituted malonates, aliphatic amines, and ortho-substituted phenols were all determined to be effective in the reaction. A domino [Rh(CO)₂Cl]₂-catalyzed allylic alkylation/Pauson-Khand reaction was developed which allows the rapid synthesis of bicyclopentenone products from simple, readily available starting materials. The first application of the Pauson-Khand reaction to the synthesis of azabridged bicyclic structures is also described. Various cis-2,6-disubstituted piperidines were cyclized to the corresponding azabridged bicyclopentenones is high yields often in high diastereoselectivities. The effect of ring size, nitrogen substituent, and remote functionality on the Pauson-Khand substrates was studied. The methodology developed was applied to the concise, enantioselective total synthesis of the antimalarial and anticancer indole alkaloid (-)-alstonerine. Pauson-Khand reaction of a readily available enyne synthesized in four steps from L-tryptophan provided a cyclopentenone in high yield as one diastereomer. Elaboration of the Pauson-Khand product required the development of a one pot conversion of a five-membered cyclic silyl enol ether to a sixmembered lactone and the mild acylation of a glycal.
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何瑾璇. "1.矽陰離子與三羰鐵錯合物的加成反應2.銠催化之分子內Pauson-KhandReaction." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/59539413755624974374.
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碩士國立臺灣師範大學
化學研究所
91
The addition of reactive carbanions to (4-1,3-diene)Fe(CO)3 complexes at —78 ℃ and 25 ℃ produced putative homoallyl and allyl anion complexes, respectively. Reaction of the reactive intermediates with 2-(phenylsulfonyl)-3-phenyloxaziridine afforded nucleophilic substituted (4-1,3-diene)Fe(CO)3 complexes. The silicon anion (LiSiMe2Ph) is capable of addition to iron-complex. The addition affords silicon-substituted iron-complex after quenching with Davis reagent. The reaction path is similar to that of carbon nucleophiles. Quenching the reactive intermediate with trifluoroacetic acid or benzoyl chloride generated organosilicon compounds. The addition of alkyne-functionalized zinc-copper reagents to iron cation gives (4-cyclohexa-1,3-diene)Fe(CO)3 complexes with an alkyne-functionalized side-chain at C-5 position of the ring. Decomplexation of the complexes with diammonium cerium(IV) nitrate afforded cyclohexadienyne compound. Intramolecular cyclization of the alkynyl-substituted cyclohexa-1,3-dienes using 1 mol% of Rh(I) and carbon monoxide afforded fused, bridge or spiro cyclic compounds.