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1
Black, Daniel. "Imines in copper-catalyzed cross-coupling reactions." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=102960.
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The purpose of this study was to develop new catalytic methods to mediate carbon-carbon bond forming reactions with imines under mild conditions and in a general manner. We found that copper catalysts were compatible in cross-coupling of a range of mild organometallic reagents, providing simple, efficient routes to alpha-substituted amides and amines.Chapter 2 of this thesis describes a new copper-catalyzed multicomponent synthesis of alpha-substituted amides. This reaction was developed based upon previous work in this laboratory, which showed that palladium catalysts were competent in Stille-type cross-coupling of imines, acid chlorides, and organostannanes. While providing a mild method of generating the amide products, a more general procedure able to incorporate a wider range of organostannanes was sought. This chapter details the development of a copper-catalyzed protocol, which, as well as performing the cross-coupling under mild reaction conditions, proceeds with a diverse range of aryl-, heteroaryl-, and vinyl-substituted organostannanes and employs an inexpensive and readily available catalyst. Through this system, control over regioselectivity of addition to alpha,beta-unsaturated imines is also possible.
Chapter 3 demonstrates that, in addition to organostannanes, other substrates are viable in copper-catalyzed cross-coupling with imines and acid chlorides. Herein, the coupling of terminal alkynes with imines and acid chlorides is described, leading to an efficient synthesis of tertiary propargylamides directly from simple starting materials. This synthesis incorporates a wide variety of substituted imines, acid chlorides/chloroformates, and terminal alkynes, providing a rapid synthesis of these useful building blocks (reaction completion in only 15 minutes). In addition, the process is shown to work with aza-aromatic heterocycles, such as pyridine, where the alkynylation occurs exclusively at the 2-position.
Chapter 4 describes the utility of these rapid multicomponent reactions, where the products are directly converted into oxazole heterocycles. Copper-catalyzed- and zinc-catalyzed protocols are developed for the synthesis of secondary propargylamides from silyl-imines, acid chlorides, and terminal alkynes. The secondary propargylamide products are then, in a one pot sequence, transformed into trisubstituted oxazoles.
Chapter 5 describes the development of an atom-economical, non-toxic alternative to the organotin coupling described in Chapter 2. This involves the use of tri- and tetraorgano-indium reagents, which can transfer all of their organic groups in a copper-catalyzed coupling with imines and acid chlorides. This reaction shows good functional group compatibility and further expands the scope of alpha-substituted amides and N-protected amines that can be synthesized through mild copper catalysis.
Chapter 6 explores the enantioselective alkynylation of nitrogen-containing heterocycles. As described in Chapter 3, heterocycles such as pyridine can undergo copper-catalyzed 1,2-addition with terminal alkynes upon activation by chloroformates. As this process generates a stereocenter, it is possible to introduce enantio-control into the reactions by using a chiral copper catalyst. With ligands from the PINAP series, enantioselectivities of up to 84% can be induced in the coupling of nitrogen-containing heterocycles (e.g., quinoline), chloroformates, and terminal alkynes. This provides a mild and simple synthesis of chiral 2-alkynyl-1,2-dihydroquinolines directly from simple starting materials.
2
Wong, Zackary L. (Zackary Leland). "Copper-catalyzed enantioselective stereodivergent synthesis of amino alcohols." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/103506.
Full textAbstract:
Thesis: S.M., Massachusetts Institute of Technology, Department of Chemistry, 2016.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 46-50 (first group)).
Different stereoisomers of bioactive molecules can have distinct activities in biological systems. For this reason, it is routine procedure in the drug discovery and development process to prepare the full matrix of possible stereoisomers of drug candidates for biological evaluation and to determine the stereochemical purity of these molecules. Despite many recent advances in asymmetric synthesis, the development of general and practical strategies that are fully divergent and give rise to all stereoisomers of products bearing multiple contiguous stereocenters remains a significant challenge. Herein we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastero- and enantioselectivity. Specifically, these amino alcohol products were synthesized using the sequential copper hydride-catalyzed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of these amino alcohol products, which contain up to three contiguous stereocenters. Catalyst control and stereospecificity were simultaneously leveraged to attain exceptional control of the product stereochemistry. Beyond the utility of this protocol, the strategy demonstrated here should inspire the development of methods providing complete sets of stereoisomers for other valuable synthetic targets.
by Zackary L. Wong.
S.M.
3
Huang, Zeyu. "Synthesis of Multifunctional Organoboron Compounds by Copper-Catalyzed Enantioselective Reactions:." Thesis, Boston College, 2017. http://hdl.handle.net/2345/bc-ir:107346.
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Thesis advisor: Amir H. HoveydaChapter 1. We have developed a catalytic method for enantio- and SN2’-selective allylic substitution of commercially available diborylmethane to trisubstituted allylic phosphates (pin = pinacolato). The transformations are catalyzed by NHC–Cu complexes (NHC = N-heterocyclic carbene). Products bearing quaternary stereogenic carbon centers are obtained in up to 86% yield (after oxidation), >98:2 SN2’/SN2 selectivity and 95:5 enantiomeric ratio (e.r.). Chapter 2. We have developed a facile multicomponent catalytic process that begins with a chemo- and site-selective copper–hydride addition to allenyl-B(pin) followed by enantioselective conjugate addition of the resulting allylcopper intermediate to α,β-unsaturated malonate, generating products that contain a stereogenic center and an easily functionalizable alkenyl-B(pin) group in up to 84% yield, >98:2 E/Z selectivity and 96:4 enantiomeric ratio. The transformations are catalyzed by chiral Cu complexes derived from commercially available bisphosphines and CuCl
Thesis (MS) — Boston College, 2017
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
4
Takeda, Momotaro. "Copper-Catalyzed Asymmetric Allylic Substitution with Organo- and Silylboronates." 京都大学 (Kyoto University), 2014. http://hdl.handle.net/2433/188504.
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Meng, Fanke. "Design of Copper-Catalyzed Multicomponent Reactions and Applications to Natural Product Synthesis." Thesis, Boston College, 2015. http://hdl.handle.net/2345/bc-ir:104876.
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Thesis advisor: Amir H. HoveydaChapter 1. Ligand-Controlled Site-Selective NHC–Cu-Catalyzed Protoboration of Monosubstituted Allenes. Site-selective proto–boryl additions to monosubstituted allenes promoted by NHC–Cu complexes are disclosed. Synthetically useful 1,1-disubstituted and Z-trisubstituted alkenylboron compounds are afforded in high efficiency (71%–92% yield) and site selectivity (88% to >98%) through proper choice of NHC ligands. Mechanistic study with the assistance of DFT calculations indicates that protonation of 2-boron-substituted allylcopper complex occurs through six-membered cyclic transition state. The utility of this protocol is demonstrated through application to fragment synthesis of an antibiotic macrolide natural product elansolid A. Chapter 2. Cu-Catalyzed Chemoselective Copper–Boron Additions to Monosubstituted Allenes Followed by Allyl Additions to Carbonyl Compounds. The first examples of catalytic generation of 2-boron-substituted allylcopper species and their in situ use for C–C bond formation are described. The reactions are performed in the presence of bisphosphine– or NHC–Cu complexes at 22 oC. High-value alcohol-containing alkenylboron compounds are provided in high efficiency (68–92% yield after oxidation) and stereoselectivity (88:12 to >98:2 dr). The reactions proceed with exclusive γ-addition mode through a cyclic six-membered transition state. Enantioselectivity can be achieved with chiral bisphosphine ligands in up to 97:3 enantiomeric ratio. Chapter 3. Chemo-, Site- and Enantioselective Copper–Boron Additions to 1,3-Enynes Followed by Site- and Diastereoselective Additions of the Resulting Allenylcopper Complexes to Aldehydes. Catalytic enantioselective multicomponent reactions involving 1,3-enynes, aldehydes and B2(pin)2 are described. The resulting products contain a primary C–B(pin) bond, as well as alkyne- and hydroxyl-substituted tertiary stereogenic centers. A critical feature is high enantioselectivity of the initial Cu–B addition to an alkyne-substituted terminal alkene. The key mechanistic issues are investigated by DFT calculations. Reactions are promoted in the presence of the Cu complex of an enantiomerically pure C1-symmetric bisphosphine and are complete in 8 h at ambient temperature. Products are generated in 66–94% yield (after oxidation or catalytic cross-coupling), 90:10 to >98:2 diastereomeric ratio, and 85:15–99:1 enantiomeric ratio. Aryl-, heteroaryl-, alkenyl-, and alkyl-substituted aldehydes and enynes are suitable substrates. Utility is demonstrated through catalytic alkylation and arylation of the organoboron compounds as well as applications to synthesis of fragments of tylonolide and mycinolide IV. Chapter 4. Multifunctional Alkenylboron Compounds through Single-Catalyst-Controlled Multicomponent Reactions and Their Applications in Scalable Natural Product Synthesis. A facile multicomponent catalytic process that begins with a chemo-, site- and diastereoselective copper–boron addition to a monosubstituted allene followed by addition of the resulting boron-substituted organocopper intermediate to an allylic phosphate, generating products that contain a stereogenic center, a monosubstituted alkene and an easily functionalizable Z-trisubstituted alkenylboron group in up to 89% yield with >98% branch selectivity and stereoselectivity and an enantiomeric ratio greater than 99:1. The copper-based catalyst is derived from a robust heterocyclic salt that can be prepared in multigram quantities from inexpensive starting materials and without costly column chromatography purification. The utility of the method is demonstrated through enantioselective synthesis of gram quantities of two natural products, rottnestol and herboxidiene/GEX1A. Chapter 5. Cu-Catalyzed Enantioselective Allyl and Propargyl 1,6-Conjugate Additions through 3,3’-Reductive Elimination. Catalytic enantioselective 1,6-conjugate additions of allyl-type nucleophiles promoted by NHC–Cu complexes are reported. Propargyl and 2-boron allyl 1,6-conjugate products are formed in high efficiency, diastereo- and enantioselectivity. The unique mechanistic feature is that the transformations proceed through Cu-catalyzed 3,3’-reductive elimination, that is unprecedented for copper catalysis. Further mechanistic study and application to complex molecule synthesis will be conducted
Thesis (PhD) — Boston College, 2015
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
6
Dong, Wanrong [Verfasser]. "Rhodium-catalyzed direct C-H functionalizations of sulfoximines and copper-catalyzed enantioselective synthesis of dihydropyrazoles / Wanrong Dong." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2014. http://d-nb.info/1057036587/34.
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McIntosh, Melissa Clark Timothy B. "Copper-catalyzed diboration of ketones : facile synthesis of tertiary a-Hydroxyboronate esters /." Online version, 2010. http://content.wwu.edu/cdm4/item_viewer.php?CISOROOT=/theses&CISOPTR=336&CISOBOX=1&REC=11.
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Ou, Jun, and 欧军. "Asymmetric reactions induced by phase-tagged phosphoric acid organocatalysts and copper hydride-catalyzed reductions of unsaturatedthioesters." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47849708.
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Two syntheses of non-cross-linked polystyrene-supported TADDOL-based
phosphoric acid organocatalyst have been developed. The optimal polymer-supported
catalyst 2.29d exhibited comparable catalytic activity to its small molecule
counterpart in asymmetric Mannich-type reactions, and the syntheses of several chiral
β-amino esters were demonstrated using 2.29d as catalyst. However, when this
TADDOL-based phosphoric acid was immobilized on a polystyrene cross-linked with
1,4-bis(4-vinylphenoxy)butane, ie. JandaJelTM, the catalytic activity diminished in the
first recycling and reuse of the catalyst.
Building on the success of the immobilization of chiral phosphoric acid, a more
robust phase-tagged BINOL-based phosphoric acid organocatalyst was developed.
By taking advantage of a tetraarylphosphonium salt as a solubility-controlling group,
a widely-used BINOL-based phosphoric acid, TRIP (3.1), was introduced onto a
tetraphenylphosphonium salt to produce a phosphonium salt-tagged phosphoric acid
catalyst 3.3e. After systematic optimizations of reaction conditions, it was found that
the catalyst 3.3e with PF6
as counteranion exhibited the best performance in terms of
enantioselectivity. Catalyst 3.3e was proved to be highly effective in asymmetric
Friedel-Crafts reaction of indoles because it was shown to be recyclable and reusable
after six cycles without loss of catalytic activity.
Based on our previous studies on the reduction of unsaturated thioesters catalyzed
by (BDP)CuH, further investigation of ligand effects revealed that in addition to BDP,
dppf was also an effective ligand for the simple reduction of 5.8. In the
stoichiometric reduction of unsaturated thioester 5.8, dppe and dppf were both
efficient ligands for copper hydride that could convert 5.8 to aldehyde 5.18 in the
presence of TMSCl, without the formation of the undesired enol ester 5.17, which was
a major product when stoichiometric amounts of Stryker’s reagent was employed.
When 5.30 bearing both a saturated and unsaturated thioester was reduced under these
conditions, only the enethioate functional group underwent reaction to yield the
mono-reduced product 5.31 while the saturated thioester functional group remained
inert.
The desymmetrizing reductive aldol reactions of symmetrical keto-enethioates
6.19, 6.22, 6.24 and 6.26 catalyzed by in situ generated chiral copper hydride were
investigated. After a screening of the reaction conditions, TaniaPhos L8 was found to
be the most effective chiral ligand to achieve high ee and yields. Under the optimum
reaction condition (5 mol% Cu(OAc)-H2O and L8 with 2.0 eq. PhSiH3), a range of
keto-enethioates smoothly underwent desymmetrizing reductive aldol cyclizations,
offering bicyclic or polycyclic β-hydroxythioesters (6.28a-6.32a, 6.37a-6.47a) in 35-
84% yield and 30-97% ee with high diastereoselectivity. The addition of 5 mol% of
bipyridine as additive resulted in an accelerated reaction rate in all of the reductions of
keto-enethioates. The crystal structure of the L8-copper bromide complex allowed
the rationalization of the major enantiomer (eg. 6.48a), in which all of the substituents
are cis, to be a result of a reductively generated (Z)-thioester enolate reacting through
a Zimmerman-Traxler transition state.
This stereochemical outcome is in contrast to the reduction of the analogous
oxoesters, which yield trans β-hydroxyesters, (eg. 6.54b), as the major products.
Several proposals to explain the divergent stereochemistry, including the
predominance of a Zimmerman-Traxler transition state of (E)-enolates or subsequent
retroaldol rearrangements, were discussed. The retroaldol rearrangement has been
observed in the conversion of 6.48a to 6.57c, in which there was retention of the
configuration at C5 and a perfect conservation of enantiomeric purity.published_or_final_version
Chemistry
Doctoral
Doctor of Philosophy
9
Ota, Yusuke. "Synthesis of Nitrogen-Containing Polycyclic Compounds through Copper-Catalyzed Multi-Component Reaction." 京都大学 (Kyoto University), 2010. http://hdl.handle.net/2433/120509.
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Lonca, Geoffroy. "Development of new reactions of organic synthesis catalyzed by gold and copper." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLX057/document.
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Cette thèse décrit le développement de nouvelles méthodes de catalyse à l’or et au cuivre pour la synthèse de composés hétérocycliques et de produits trifluorométhylés.Dans un premier temps, une synthèse d’allènes trifluorométhylés par catalyse à l’or a été développée, dont l’étape clé est un transfert d’hydrure 1,5. Cette méthode donne accès de manière efficace et sélective à une large gamme d’allène perfluoroalkylés dont le potentiel synthétique a également été démontré.Le pouvoir catalytique de l’or a alors été utilisé dans une synthèse de 2H-1,3-oxazines reposant sur une cyclisation de type 6-endo d’azido alcynes. Cette méthode donne accès dans des conditions très douces à une gamme sans précédent d’oxazines polysubstituées avec d’excellents rendements.Dans un dernier temps, une méthode d’hydrofonctionnalisation radicalaire d’alcènols catalysée au cuivre. La stratégie impliquée repose sur une abstraction d’hydrogène 1,5, dans laquelle un groupement benzyloxy joue le rôle de donneur d’hydrogèneThis manuscript presents the development of gold- and copper-catalyzed methods for the synthesis of heterocyclic compounds and trifluoromethylated products.Firstly, a gold-catalyzed synthesis of trifluoromethyl allenes was developed, relying on a 1,5 hydride shift. This method allows to access, in a very efficient and selective way, a large range of perfluoroalkylated allenes, of which the synthetic potential was also demonstrated.Afterwards, the catalytic power of gold was then used in a synthesis of 2H-1,3-oxazines, relying on a 6-endo type cyclization of azide-yne substrates. This methods allows to access, in very mild condition, an unprecedently large range of polysubstituted oxazines in excellent yields.Finally, a method for the copper-catalyzed radical hydrofunctionalization of alkenols was developed. The strategy involved relies on a 1,5 hydrogen abstraction, in which a benzyloxy moiety plays the role of the hydrogen donor
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Norinder, Jakob. "Asymmetric Synthesis and Mechanistic Studies on Copper(I)-Catalyzed Substitution of Allylic Substrates." Doctoral thesis, Stockholm : Department of Organic Chemistry, Stockholm University, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1031.
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Wu, Fan. "Iodide-Catalyzed Alkene Oxyamination Reactions for the Synthesis of Nitrogen-Containing Heterocycles." University of Toledo / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1576248441561743.
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Barabe, Francis. "Gold(I)-Catalyzed Synthesis of Polycyclic Frameworks Related to Terpenes: Selective Divergent Synthesis of Fused Carbocycles." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/29055.
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Gold catalysis has become an important tool to achieve highly chemoselective p-acid activation. Exceptional reactivity and selectivity are often encountered under mild reaction conditions. These properties have made gold(I) complexes suitable catalysts for tremendous applications in the total synthesis of natural products. The first chapter will highlight a number of total syntheses using gold catalysis as a key step.
The second chapter will cover our application of the gold(I)-catalyzed 6-endo-dig carbocyclization for the synthesis of bridgehead-substituted scaffolds and its use toward the synthesis of PPAP natural products. This research has opened our eyes to the utility of biphenylphosphine ligands, particularly JohnPhos, in gold(I)-catalysis.
The reactivity and selectivity exhibited by gold(I) complexes is modulated by the nature of the ancillary ligand. Recent research rationalizes the impact of these ligands on the divergent reactivity observed between cationic and carbenoid intermediates. Our desire to favor the 6-endo-dig pathway has led us toward the discovery of another example of the diagonal reactivity that NHC carbene and biphenylphosphine ligands can bring to gold(I)-catalysis. Chapter three will explain the development of a selective gold-catalyzed synthesis of fused carbocycles
.
Our selective divergent synthesis of fused carbocycles, combined with the Diels–Alder reaction, has brought new synthetic opportunities. Chapter four will describe our approach toward the synthesis of various polycyclic diterpene-related frameworks. Starting with a unique linear precursor, we have developed a new “one-pot” process for the synthesis of three different polycyclic compounds related to the terpenoid family. The facile modulation of the linear precursor and the use of different dienophiles during the Diels–Alder reaction could enable the synthesis of diverse polycyclic analogues based on three principal frameworks.
The gold(I)-catalyzed synthesis of fused carbocycles reached some limitations during our study. Regioselective control was found to be substantially more challenging, with terminal alkynes or alkynes bearing a sterically and electronically neutral methyl substituent. In chapter five, we will discuss how the complementarity of silver(I) catalysis to gold(I) catalysis enabled the selective divergent synthesis of three different fused carbocycles from a unique precursor. Moreover, copper(I) catalysis has given access to the 6-endo-dig pathway on terminal alkynes without the formation of a vinylidene intermediate.
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Brown, Michael Kevin. "CU-catalyzed enantioselective conjugate addition of organometal reagents to unsaturated carbonyls : an enantioselective total synthesis of clavirolide C." Thesis, Boston College, 2008. http://hdl.handle.net/2345/964.
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Li, Jihui. "Copper-Catalyzed Domino C-N Bond Formation for Synthesis of N-Containing Compounds (Benzimidazoles, Imidazoles, and Guanidines) - Approach toward Total Synthesis of Natural Product Raputindoles." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA112130.
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Cette thèse est constituée de trois parties : 1) Le contexte bibliographique, 2) le développement de réactions domino cupro-catalysées et 3) une approche vers la synthèse totale des raputindoles.La première partie introduit d’abord le concept de réactions domino ainsi que leurs applications, puis les réactions catalysées par du cuivre permettant de former des liaisons C-N sont passées en revue en incluant les couplages de Ullmann, Goldberg et de Chan-Lam, les séquences d’activation oxydante de liaisons C-H/formation de liaison C-N, l’insertion de nitrènes et l’hydroamination de liaisons C-C multiples. En se basant sur ces réactions élémentaires permettant de former une liaison C-N unique, les développements récents de réactions domino sont ensuite détaillés.La deuxième partie peut être subdivisée en 3 sections : 1) la synthèse de benzimidazoles, 2) la synthèse d’imidazoles and 3) la synthèse de guanidines. Un rappel des méthodes existantes pour la synthèse de ces motifs est proposé dans chaque section. Notre travail, basé sur la formation de liaisons C-N multiples selon une séquence cupro-catalysée domino, est ensuite détaillé. Celui-ci nous a permis d’aboutir au développement de voies d’accès aux benzimidazoles, en utilisant une réaction séquentielle catalysée par du cuivre en présence d’oxygène à partir d’acides boroniques et d’amidines, à la synthèse d’imidazoles par une réaction de di-amination d’alcynes vrai par des amidines et à l’obtention de guanidines et de 2-aminobenzimidines par une réaction à 3 composant. Ces réactions domino montrent une bonne efficacité et permettent d’assembler des hétérocycles à partir de précurseurs aisément accessibles.La dernière partie est consacrée à la synthèse des raputindoles. La structure, les activités et les réactions clé pour la construction de ces alcaloïdes sont discuté d’abord, nous amenant à proposer une rétrosynthèse pour accéder à ces molécules. Les réactions qui ont retenues notre attention pour construire ces molécules sont une annelation [3+2] irido-catalysée d’acides o-formylarylboronique et de 1,3-diènes, la synthèse de Leimgruber-Batcho pour obtenir des indoles et une séquence d’alkylboration-protodéboration. A partir de cela 3 stratégies ont été évaluées, montrant que l’accès à ce type de composé naturel est envisageable en combinant ces étapesThis thesis consists in three parts: bibliographic background, copper-catalyzed reactions for synthesis of N-containing compounds, approach to the synthesis of raputindoles.The first part introduces the domino reactions and their applications, then, copper-mediated reactions for construction of C-N bond formation are reviewed including Ullmann, Goldberg and Chan-Lam coupling, oxidative C-H activation/C-N formation, insertion of nitrenes and carbenoids, and hydroamination of multi-C-C bonds. This can be used as guides to design domino reaction. Following these copper-mediated single C-N bond formation reactions, recent developments of copper-catalyzed domino reactions for synthesis of heterocycles are described.The second part can be divided into three sections: 1) synthesis of benzimidazoles, 2) synthesis of imidazoles and 3) synthesis of guanidines. Each section summarizes the existing methods used for their synthesis. Following it, our synthetic work involving copper-catalyzed C-N bond formation domino reactions is discussed in detail. Our objectives include the synthesis of benzimidazoles through copper-catalyzed sequential reaction of benzamidines and boronic acids, synthesis of imidazoles via copper-catalyzed domino reaction of benzamidines and acetylenes, and synthesis of guanidines and 2-aminobenzimidazoles by Cu-catalyzed three-component reaction of cyanamides, boronic acids and amines. These copper-catalyzed domino reactions show high efficiencies from readily available and simple starting materials.The last part is about the total synthesis of raputindoles. The structure and bioactivities of raputindoles and key reactions for the total synthesis of raputindoles are introduced first, the synthetic strategies are then proposed on basis of relative synthetic methods. The key reactions we use for the synthesis of raputindoles are iridium catalyzed [3+2] annulation of o-formylarylboronic acids and 1,3-dienes, Leimgruber-Batcho indole synthesis, transition-metal catalyzed SN2 substitution and alkylborylation-protondeborylation. According to the three strategies we proposed, lots of relative reactions were investigated. The results show that it is possible to synthesize the raputindole molecules based on the iridium catalyzed [3+2] annulation of 2-formylarylboronic acids and 1,3-dienes
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Gilligan, Ruth Elaine. "Copper-catalyzed C-H arylation : development of new methodology and its application to the total synthesis of staurosporinone." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607788.
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Husmann, Ralph [Verfasser]. "Synthesis and application of silylated pyrrolidines enantioselective organocatalytic synthesis of a-trifluoromethyl a-amino acid derivatives and copper-catalyzed multicomponent reactions / Ralph Husmann." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2011. http://d-nb.info/1018190465/34.
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Chatalova, Sazepin Claire. "Radical methods for the synthesis of fluoroalkanes and fluoromethyl aryl ethers and copper-catalyzed three-component carboetherification of alkenes." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/55907.
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Fluorinated molecules have become popular compounds among pharmaceuticals. The introduction of fluorine atoms on bioactive compounds has indeed the potential to improve their biophysical properties. Given the utility of fluorinated substituents on pharmaceuticals, fluorine chemistry has become an area of intensive research. Despite the progress made in selective fluorination, however, radical fluorination has been limited notably due to the paucity of atomic fluorine sources. In this thesis, the uncovering of new atomic fluorine sources and the development of new radical fluorination methods will be described.
Chapter 1 presents the importance of fluorinated molecules and the currently available fluorinating agents. A discussion on radical fluorination is presented that includes the most recent advances in the field.
In Chapter 2, the exploratory work on the ability of electrophilic N—F fluorinating agents to transfer fluorine to alkyl radicals is detailed. Peresters were chosen as radical precursors and reacted with traditionally electrophilic fluorine sources, NFSI and Selectfluor®. Under those conditions, various fluoroalkanes could be synthesized in good yields.
A radical fluorination method subsequently developed using Selectfluor® is described in Chapter 3. The ability of phenoxyacetic acid derivatives to undergo fluorodecarboxylation under UV-light excitation using Selectfluor® was demonstrated. The methodology was successfully applied to the synthesis of mono- and difluoromethyl aryl ethers in 40 to 86% yields.
Chapter 4 details the application of the photofluorodecarboxylation to the synthesis of trifluoromethyl aryl ethers. It was found that the wavelength required for the substrate’s excitation led to the decomposition of the desired products. A method using benzophenone as a photosentizer was developed allowing the use of another wavelength to promote the reaction, which proved to be substrate dependent. The use of a faster fluorine transfer agent, XeF2, allowed the synthesis of trifluoromethoxy arenes in good yields.
A copper catalyzed difunctionalization of alkenes, developed in collaboration with Prof. Jieping Zhu, is presented in Chapter 5. This reaction allows the direct introduction of alkyl nitriles via C—H activation. A C—O bond and a C—C bond were created in a single step. A wide range of α substituted styrenes were difunctionalized in yields up to 82%.Science, Faculty of
Chemistry, Department of
Graduate
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HU, JIEYU. "COPPER(I) CATALYZED EXO-SELECTIVE [CN+C+CC] 1,3-DIPOLAR CYCLOADDITIONS and STUDIES TOWARDS THE TOTAL SYNTHESIS OF KAITOCEPHALIN." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1269965489.
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Andrella, Nicholas Orlando. "Synthesis of Organo-fluorine Compounds by Metal Complex-mediated and -Catalyzed Transformations of Fluoro-alkenes and Fluoro-arenes." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39509.
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The prevalence of fluorine in natural products is scarce. There are but a handful of compounds that have been discovered to date. This could be largely attributable to the occurrence of fluorine in nature as fluoride (F-). — One might recognize such nomenclature from the ingredients list on a toothpaste tube — In fact, naturally occurring fluoride is most commonly found as fluorite (CaF2) or cryolite (Na3AlF6). As such, the introduction of fluorine via biological pathways has been limited to use of aqueous F- (a very poor nucleophile). This fact — coupled with its naturally low concentration in water — has created the ripe conditions for this shortage. In a way this has proven fertile for synthetic chemists because nature has not yet evolved a method for the deconstruction of partially or fully fluorinated compounds.
Considering the above, as synthetic methodologies for the construction of carbon-fluorine bonds became available, so too did the discovery of their valuable properties. So beneficial are these properties that C-F bond-containing compounds have become commonplace in many households throughout the world. For example, practically every home relies on these compounds for use in their refrigerators. Other examples of useful fluorinated materials include blowing agents, non-stick coatings, pharmaceuticals, agrochemicals, liquid crystals, and lubricants.
With all these applications and seemingly easy availability of these compounds, it is interesting to learn that original synthetic methods are still being employed today. As such, the objective of this Thesis is to develop ‘greener’ routes for the synthesis of fluorocarbons. We hypothesized that by studying transition metal-fluoroalkyl complex-mediated reactions, a more efficient catalytic system could be developed. A foreseen complication arises from the thermodynamic stability of C-F, transition metal-F and transition metal-CRF bonds. Improvements to overcome these caveats include the use of first-row late transition metal complexes. Presented herein are additions to this body of knowledge by expanding on the reactivity of nickel, copper and silver fluoroalkyl complexes.
The approach applied in this work, in line with ‘green’ chemistry principles, was to source readily available fluorinated reagents, i.e. fluoroalkenes and fluoroarenes, to reduce the number of steps for the synthesis of new fluorinated compounds. Chapter 2 builds on the well-established oxidative cyclization of C2 fluoroalkenes to nickel (0), which yields new C4 units. The use of a bulky N-heterocyclic carbene ligand was found to enhance reactivity by reducing the coordination number at nickel. Examples of room temperature Cα-F and Ni-CF bond activation and functionalization reactions are presented. Chapters 3, 4 and 5 re-examine the insertion of fluoroalkenes into silver and copper fluorides and hydrides. Building on precedent of addition reactions to hexafluoropropene, this fluoroalkene was examined first. In so doing, a versatile and inexpensive copper heptafluoroisopropyl reagent was developed (Cu-F addition to (CF3)CF=CF2. With easy access to new heptafluoroisopropyl complexes, they were systemically studied for their applications in catalysis. This revealed key features, particularly the lability of the M-hfip bond, which could be detrimental to catalytic reactions. As such, a nickel complex-mediated carbonylative heptafluoroisopropylation reaction and copper complex-mediated nucleophilic addition to electrophiles were developed. When a copper hydride was used instead, the in situ generated fluoroalkyl [Cu-H addition to (CF3)CF=CF2] was susceptible to β-fluoride elimination. Chapter 4 expands this methodology to achieve the catalytic consecutive hydrodefluorination of fluoroalkenes, demonstrating the scope and limitations of this system. Furthermore, the critical role of the phosphine ligand in accessing an L3Cu-H addition and unusual β-fluoride elimination mechanism is highlighted. However, tetrafluoroethylene proved resistant to this reaction because the fluoroalkyl resting state of this alkene, Cu-CF2CF2H, is unusually robust. Chapter 5 investigates the utility of this fragment and others in C(sp2)-RF cross-coupling and nucleophilic substitutions. With focus on new routes for late stage fluorination and examples of nickel (0) complex-catalyzed selective C-F bond functionalization reactions, Chapter 5, continues studies for low-temperature and DMAP-assisted conditions for aryl-F cross-coupling reactions with boronic acid esters.
Lastly, Chapter 6 reviews the advances presented in this Thesis, provides a link to the expected lasting impacts and attempts to provide guidance to future research on transition-metal complexes in the synthesis of C-F or C-RF containing compounds. Moreover, with the introduction of a new hydrodefluorination technology, previously scarce fluoroalkenes (e.g. 1,2-difluoroethylene) can now be used more freely, potentially leading to the development of new refrigerants or materials applications.
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Komati, Rajesh. "Cu (II) Catalyzed Gateways In The Synthesis of Acridine Derivatives and Their Biological Evaluation as Anti-Cancer Drugs." ScholarWorks@UNO, 2014. http://scholarworks.uno.edu/td/1818.
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Telomeres are nucleoprotein complexes found at the ends of linear eukaryotic chromosomes. Telomeres consist of a short sequence of repetitive double stranded DNA, TTAGGG repeats in humans (and all mammals), and a complex of 6 proteins, termed the shelterin complex. The length of the telomeres varies greatly between species, from approximately 300 base pairs in yeast to many 10-15 kilo bases in humans, because of the end replication problem this length get shorten with each cell division and ultimately leads to cell death. However the immortal eukaryotic cells and some transformed human cells over come this incomplete end replication problem with the use of enzyme called Telomerase. Telomerase is a ribonucleoprotein enzyme that adds a specific DNA sequence repeats (TTAGGG) to the 3¢ end of DNA strands in the telomere regions. However from the telomerase activity studies, it was concluded that telomerase is active in almost 90% of human cancers but not in normal somatic tissues. Finally, the low or transient expression of telomerase in normal tissues, including normal stem cells, and the generally longer telomeres in normal cells versus tumor cells provide a degree of tumor specificity to telomerase-based drugs and reduce the probability of toxicity to normal tissue. All of these factors suggest that cancer drugs based on telomerase might have a broad therapeutic window.
This dissertation focusing on the synthesis of acridine derivatives that have the capability to inhibit the enzyme telomerase. Several N-acridyl maleimide (NAM), N-acridyl succinimide (NAS) and N-acridyl phthalimide (NAP) derivatives have been synthesized and evaluated for their anti cancer activity against various cancer cell lines. While synthesizing acridine derivatives it was required to form the C-N bonds at various stages. Developed a copper-nicotinic acid complex, which catalyzes the coupling of aryl halides with N-formyl amines and cyclic imides to form C-N bond. Explored Cu (II) catalyzed formation of C-N bond by coupling aryl halides with various N-nucleophiles such as formamide, N,N-dimethyl formamide, N-formyl amines and various cyclic imides.
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Decan, Matthew. "The Copper(I)-catalyzed Azide–Alkyne Cycloaddition: A Modular Approach to Synthesis and Single-Molecule Spectroscopy Investigation into Heterogeneous Catalysis." Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31882.
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Click chemistry is a molecular synthesis strategy based on reliable, highly selective reactions with thermodynamic driving forces typically in excess of 20 kcal mol-1. The 1,3-dipolar cycloaddition of azides and alkynes developed by Rolf Huisgen saw dramatic rate acceleration using Cu(I) as a catalyst in 2002 reports by Barry Sharpless and Morten Meldal enabling its click chemistry eligibility. Since these seminal reports, the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) has become the quintessential click reaction finding diverse utility. The popularity of the CuAAC has naturally led to interest in new catalyst systems with improved efficiency, robustness, and reusability with particular focus on nanomaterial catalysts, a common trend across the field of catalysis. The high surface area of nanomaterials lends to their efficacy as colloidal and heterogeneous nanocatalysts, but the latter boasts the added benefit of easy separation and recyclability. With any heterogeneous catalyst, a common question arises as to whether the active catalyst species is truly heterogeneous or rather homogeneous through metal ion leaching. Differentiating these processes is critical, as the latter would result in reduced efficiency, higher cost, and inevitable environmental and heath side effects.
This thesis explores the CuAAC from an interdisciplary approach. First as a synthetic tool, applying CuAAC-formed triazoles as functional, modular building blocks in the synthesis of optical cation sensors by combining azide and alkyne modified components to create a series of sensors selective for different metal cations. Next, single-molecule spectroscopy techniques are employed to observe the CuNP-catalyzed CuAAC in real time. Combining bench-top techniques with single-molecule microscopy to monitor single-catalytically generated products proves to be an effective method to establish catalysis occurs directly at the surface of copper nanoparticles, ruling out catalysis by ions leached into solution. This methodology is extended to mapping the catalytic activity of a commercial heterogeneous catalyst by applying super-localization analysis of single-catalytic events. The approach detailed herein is a general one that can be applied to any catalytic system through the development of appropriate probes. This thesis demonstrates single-molecule microscopy as an accessible, effective, and unparalleled tool for exploring the catalytic activity of nanomaterials by monitoring single-catalytic events as they occur.
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Lee, Elaine C. "Improved synthesis and application of planar-chiral nucleophilic catalysts in asymmetric reactions and copper-catalyzed enantioselective N-H insertion reactions." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/39741.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2007.Vita.
Includes bibliographical references.
The development of an improved synthesis of nucleophilic planar-chiral catalysts is described in Chapter 1. This route is amenable to scale-up and preparative chiral HPLC is unnecessary to resolve the racemic catalysts. Using planar-chiral catalysts, two synthetic methodology projects have been developed: Chapter 2 describes the first asymmetric synthesis of trans P-lactams, and Chapter 3 describes the asymmetric synthesis of tertiary a-chloroesters. In the chapter describing the asymmetric synthesis of trans [beta]-lactams, we present mechanistic data supporting a novel mechanism, in which the N-triflylimine, rather than the ketene, reacts with the catalyst first. In the chapter describing the asymmetric synthesis of tertiary a-chloroesters, we introduced an under-utilized commercially available chlorinating reagent (2,2,6,6-tetrachlorocyclohexanone). Finally, in chapter 4, the Cu-catalyzed asymmetric synthesis of [alpha]-aminoesters via an N-H insertion is described. We have demonstrated that carbamates such as BocNH2 and CbzNH2 are efficient coupling partners in reactions with a-diazoesters to generate highly useful Boc- or Cbz-protected a-aminoesters.
by Elaine C. Lee.
Ph.D.
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Jones, Carrie Preston. "Development of a copper-catalyzed amidation-base-promoted cyclization sequence for the synthesis of 2-aryl- and 2-vinyl1-4 quinolones." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/41771.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2007.Vita.
Includes bibliographical references (p. 45-48).
A direct two-step method for the preparation of 2-aryl- and 2-vinyl-4-quinolones that utilizes a copper-catalyzed amidation of ortho-halophenones followed by a base-promoted Camps cyclization of the resulting N-(2-keto-aryl)amides is described. With Cul, a diamine ligand, and base as the catalyst system, the amidation reactions proceed in good yields for a range of aryl, heteroaryl, and vinyl amides. The subsequent Camps cyclization efficiently provides the desired 4-quinolones using the conditions that are described.
by Carrie Preston Jones.
S.M.
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Job, Gabriel Ethan. "Copper-catalyzed arylation of 1,2-amino alcohols. Synthesis of N-terminal, peptide helix initiators, and characterization of highly helical, capped polyalanine peptides." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/32481.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005.Vita.
Includes bibliographical references.
I. An improved Ullmann reaction for N- or O-arylation of 1,2-aminoalcohols with aryl iodides is described. The procedures enjoy several advantages over traditional methods: a substoichiometric amount of copper catalyst is employed, the reactions take place in low boiling and non-toxic solvents such as isopropanol, the reactions occur at relatively low temperatures, and a variety of non-activated aryl iodide substrates may be used. II. Recent advances in solubilization of polyalanine and helix stabilization by end capping were combined to synthesize a series of highly helical, water-soluble polyalanine peptides permitting straightforward context-free investigation of this most common helix- forming [alpha]-amino acid. Three types of peptides incorporating this helical polyalanine region were made, each for a specific purpose: structure determination by NMR; fractional helicity measurement by amide NH to ND exchange in D₂0, observed by NMR; and CD analysis. CD spectra of these helical peptides were used to directly verify an equation used for peptide structural analysis. The helix-initiating N-terminal cap (Hel) used to create the highly helical polyalanines is a synthetically modified Pro-Pro dipeptide. Hel was developed in the Kemp group a decade ago, and peptides created with it have been extensively studied in this group. However, the 18-step synthesis of Hel has hindered its use by others. Therefore, simpler analogs of Hel have been made and preliminary studies have been conducted. The simpler N-caps were synthesized in twelve steps or fewer and proved effective at helix initiation, as judged by CD spectroscopy.
(cont.) The studies reported herein have also identified an even simpler helix initiator: the dipeptide sequence .... Further evaluation of these new N-caps under conditions that are not ideal for helix formation awaits.
by Gabriel E. Job
Ph.D.
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Sun, Xuetong. "Development of a new tridentate pincer phosphine N-heterocyclic carbene ligand & Development of a copper II catalyzed three component tandem synthesis of isoindolinone derivatives." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97123.
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Two types of research were carried out in this thesis; the first section is about the development of a new phosphine-based tridentate pincer N-heterocyclic carbene ligand and examination of the catalytic activities of its transition metal compexes including conjugated addition, alkyne-aldehyde addition and Alkyne-Aldehyde-Amine (A-3) coupling reaction. The second section of the thesis is about the methodology development of an A-3 based tandem synthesis of isoindoline derivatives and gold (I) catalyzed cyclization for the synthesis of isoindolo[2,1-a]quinolines derivatives. The aim of these studies is to develop novel catalysts and synthetic methodologies that can approach conventional chemical syntheses in a "greener" manner, therefore substantially gain atom-economy, step-economy and leads to a more sustainable life.Deux types de recherches ont été accompli dans cette thèse. La première section comporte sur le développement d'un nouveau ligand carbène hétérocyclique et l'analyse de ses complexes formés avec des métaux de transitions et leur efficacité lors des additions conjuguées, d'addition alcyne-alcène et des réactions de couplage entre un alcyne, une aldéhyde et une amine (A-3). La deuxième partie de cette thèse porte sur le développement d'une méthodologie de synthèse de dérivés d'isoindoline utilisant une réaction en tandem dérivés du couplage A-3 et la synthèse de dérivés d' isoindolo[2,1-1]quinolines par cyclisation catalysée par des sels d'or(I). Le but de ces études étant de développer des méthodologies de synthèse et des catalyseurs novateurs pouvant s'appliquer à des synthèses conventionnelles et de ce fait les rendre plus "vertes", en augmentant leur économie d'atomes, économie d'étapes dans une perspective de développement durable.
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Orre, Tommy. "Synthesis of modified silica using copper catalyzed click chemistry : Finding a procedure to attach corannulene to silica using click chemistry with the goal of separating fullerene isomers." Thesis, Umeå universitet, Kemiska institutionen, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-92605.
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Linstadt, Roscoe T. H. "A. Studies In The Allylic Substitution Chemistry Of Copper Hydride B. Stereoselective Silylcupration Of Conjugated Alkynes In Micellar Media C. Palladium-Catalyzed Synthesis Of 1,3-Butadienes and [3]-[6]Dendralenes D. Synthesis Of Small Molecule Underwater Adhesives Inspired By Mussels." Thesis, University of California, Santa Barbara, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10257794.
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Copper hydride (CuH) has been shown to enable a number of selective 1,2- and 1,4-reductions when complexed with the appropriate ligand, yet the allylic substitution chemistry of CuH has been much less studied. This dissertation describes the further study of CuH to perform sequential reductions on Morita-Baylis-Hillman (MBH) adducts. Specifically: I) Selectivity in the SN2’ reduction of MBH adducts was shown to be highly dependant on the nature of the ligand used. II) The reaction of MBH alcohols was shown to involve an initial dehydrogenative silylation with PMHS, where both the oligomeric nature and electronics of the initially formed trialkoxysilyl ether intermediate are important in determining both the observed stereoselectivity, and efficiency of the substitution. III) MBH ketones could be employed in tandem SN2’/1,2-reduction sequences to arrive at stereodefined allylic alcohols with central chirality.
Vinylsilanes are versatile intermediates in organic synthesis owing to numerous methods for their transformation into other functional groups that proceed with high stereoretention. While there are numerous methods to synthesize stereodefined vinylsilanes from alkynes, many existing methods require the use of highly reactive moisture intolerant reagents and harsh reaction conditions, features that limit the functionality that can be accommodated. Even fewer of these existing methods are conducted under environmentally responsible conditions. The use of Suginome’s reagent as a moisture tolerant source of nucleophilic silicon, small catalytic quantities of a simple copper(I) salt, and an aqueous solution of TPGS-750-M as an environmentally benign nonionic surfactant, is described herein as a highly effective combination of reagents that allows for the stereoselective silylcupration of conjugated alkynes giving access to a variety of (E)-β-silyl-substituted carbonyl derivatives under environmentally responsible conditions.
This dissertation also describes the application of substituted allenoates as electrophilic butadienyl coupling partners under palladium catalysis in aqueous micellar media. The substituted allenoates could then be transformed by the methods developed herein into a variety of 2-substituted butadienes, where the methods were then extended to provide entry into a variety of substituted [3]-[6]dendralenes. Specifically: I) Application of an additive based screen allowed for evaluation of functional group tolerance in the Pd-catalyzed coupling of substituted allenoates with boronic acids. II) Curiosity driven investigations to identify boron based sp3 coupling reagents compatible with the conditions of micellar catalysis led to the identification of OBBD alkylborinate reagents as stable and isolable coupling reagents, which was the applied to the synthesis of 2-alkyl 1,3-butadienes. III) An analogous vinylallenyl coupling partner that functions formally as an electrophilic [3]dendralene synthon was proposed, and a number of synthetic routes were examined to access this molecule. Optimization of the synthetic route allowed for access to multigram quantities of this material, where it was applied to the synthesis of variously substituted [3]-[6]dendralenes.
Efforts to understand the marine mussels mechanism of strong wet adhesion has been a subject of intense scientific investigation. Analysis of the peptide sequence of mfp-5, a mussel foot protein most correlated with interactions at the interface, revealed a high proportion of charged, hydrophobic, and catechol containing residues. Described in this dissertation is the synthesis of small molecule underwater adhesives by incorporation of these key features of mfp-5. These newly designed molecules formed adhesive bilayers underwater, and were shown to replicate and even exceed mfp-5’s strong wet adhesive energy, while also being orders of magnitude smaller than both the native mussel proteins or existing biomimetic adhesive platforms. By systematically varying key portions of these small molecular adhesives, the adhesive bilayers could be transformed into molecularly uniform monolayers which were applied to the nanofabrication of organic electronic devices.
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Zhang, Yang [Verfasser], Norbert [Akademischer Betreuer] Krause, and Ralf [Gutachter] Weberskirch. "Study of total synthesis of 9α,10β- Bisangeloyloxy-7-epi-3E-agerafastin and 3-O- Feruloylcassine by copper-mediated nucleophilic substitution and gold-catalyzed cycloisomerization / Yang Zhang ; Gutachter: Ralf Weberskirch ; Betreuer: Norbert Krause." Dortmund : Universitätsbibliothek Dortmund, 2019. http://d-nb.info/1195215983/34.
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Tadd, Andrew. "Palladium and copper catalysed heterocycle synthesis." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504606.
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Ball, Catherine Jane. "Palladium- and copper-catalysed heterocycle synthesis." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:589b70fb-0823-4ccf-8b35-1883908f917d.
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A number of privileged starting materials based on aryl halide frameworks have emerged that allow access to a variety of different heterocyclic scaffolds through judicious choice of reaction conditions. This work describes efforts to develop and extend the utility of two of these general heterocycle precursors - ortho-(haloalkenyl)aryl halides A and α-(ortho-haloaryl) ketones B - in conjunction with cascade reactions involving the construction of key carbon-heteroatom bonds via palladium or copper catalysis. Chapter 1 entails an overview of the development of palladium- and copper-catalysed carbon-heteroatom bond forming processes. The application of these processes in heterocycle synthesis using ortho-(haloalkenyl)aryl halide and ortho-haloacetanilides/ α-(ortho-haloaryl) ketone precursors is also described. Chapter 2 focuses on the development of a two-step synthesis of cinnolines using ortho-(haloalkenyl)aryl halides via intermediate protected dihydrocinnoline derivatives C. Chapter 3 demonstrates how the inherent reactivity of protected dihydrocinnoline derivatives C can be harnessed to provide access to functionalised products. A brief target synthesis of a pharmaceutically-relevent cinnoline is also described. Chapter 4 details attempts to develop a novel synthesis of benzothiophenes D from both ortho-(haloalkenyl)aryl halide and α-(ortho-haloaryl) ketone precursors.
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Dharap, Y. V. "Facile synthesis of aziridines using copper hydrotalcite under microwave irradiation; synthesis of 3-substituted2(1h)-quinolinones catalyzed by hydrotalcite like anionic clays; rearrangement of α-pinene epoxide to campholenic aldehyde with modified beta zeolite catalyst and regioselective nitration of phenols with new phosphorus based ionic liquids." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2008. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/2633.
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El-Batta, Amer Adnan. "Part I, copper(I) iodide dimethyl sulfide catalyzed 1,4-addition of alkenyl groups from alkenylzirconium and alkenylzinc reagents and their application toward the total synthesis of azaspirene ; Part II, aqueous Wittig chemistry employing stabilized ylides and aldehydes." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3268346.
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Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2007.Title from first page of PDF file (viewed August 7, 2007). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 265-280).
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Topping, Chris Mark. "Design and synthesis of chiral ligands for copper catalysed asymmetric synthesis." Thesis, University of Hull, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301496.
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Campbell, Matthew James Johnson Jeffrey Scott. "I. Mechanistic studies of a copper-catalyzed electrophilic amination of diorganozinc reagents reagents by O-benzoyl N,N-dialkylhydroxylamines II. Development of a 3-Exo-Dig cyclization for the preparation of vinylidene cyclopropanes III. Total synthesis of +-polyanthellin A." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2009. http://dc.lib.unc.edu/u?/etd,2881.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2010.Title from electronic title page (viewed Jun. 23, 2010). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry." Discipline: Chemistry; Department/School: Chemistry.
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Poutrel, Pauline. "Réduction du motif vinyl-CF₃ : vers la synthèse catalytique énantiosélective de centres C-CF₃ et la synthèse diastéréosélective de monofluoroalcènes terminaux Copper‐catalyzed enantioselective formation of C−CF3 centers from β‐CF3‐substituted acrylates and acrylonitriles Stereoselective synthesis of terminal monofluoroalkenes from trifluoromethylated alkenes." Thesis, Normandie, 2020. http://www.theses.fr/2020NORMIR07.
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Ces dernières années, la chimie du fluor est devenue un domaine clé de recherche de par la présence croissante de l’atome du fluor dans les molécules issues de l’agrochimie, de l’industrie pharmaceutique et des matériaux. Il est alors nécessaire de développer de nouvelles méthodologies permettant la synthèse de ces molécules fluorées. Dans notre cas, il s’agit de mettre au point des procédures permettant l’obtention de synthons d’une part avec un centre stéréogène contrôlé comportant un motif trifluorométhyle, d’autre part avec un motif monofluoroalcène terminal. Dans un premier temps, nous avons développé une méthodologie pour la réduction catalytique asymétrique d’acrylates et d’acrylonitriles β-CF3 via la formation in-situ d’un hydrure de cuivre chiral. Dans un second temps, avons mis au point une méthodologie de synthèse de monofluoroalcènes terminaux par réduction au LiAlH4 d’acrylates β-CF3 et de styrènes α-CF3 di-, tri- ou tétrasubstituésIn recent years, organofluorine chemistry has become a key field of research thanks to the growing presence of the fluorine atom in molecules coming from agrochemistry, pharmaceutical industry and materials. It is therefore necessary to develop new methodologies for the synthesis of fluorinated molecules. In our case, we envisioned to develop procedures to obtain synthons with a stereogenic center bearing a trifluoromethyl group on the one hand, and synthons with a terminal monofluoroalkene motif on the other hand. We first developed a methodology for the catalytic asymmetric reduction of β-CF3 acrylates and acrylonitriles via the formation in-situ of a chiral copper hydride species. We then developed a methodology for the synthesis of terminal monofluoroalkenes by reduction of di-, tri- or tetrasubstitued β-CF3 acrylates and α-CF3 styrenes with LiAlH4
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Toummini, Dounia. "Arylation de nucléophiles, par catalyse au cuivre ou au fer, ou en milieu superbasique en absence de métal de transition." Thesis, Montpellier, Ecole nationale supérieure de chimie, 2014. http://www.theses.fr/2014ENCM0001.
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Cette thèse s'inscrit dans le cadre très général de la recherche de nouvelles méthodes de synthèse éco-compatibles. Dans la première partie, intitulée « Arylation catalysée au cuivre d'hétérocycles azotés par des sels d'aryldiazonium», nous avons présenté nos travaux décrivant le premier exemple d'une réaction de type Sandmeyer permettant la formation d'une liaison carbone-azote (C-N). Nos systèmes permettent, en effet, l'arylation de nucléophiles azotés, essentiellement de type pyrazole, à partir d'électrophiles d'aryldiazoniums. Les motifs obtenus, les arylpyrazoles, sont des molécules extrêmement répandues, aux nombreuses applications dans le domaine des sciences de la vie mais aussi des matériaux.Les conditions que nous utilisons sont extrêmement douces puisqu'elles ne font appel qu'à des quantités catalytiques de cuivre et d'acide acétique. Par ailleurs, ce système fonctionne à température ambiante sans nécessiter la présence de ligands, additifs ou bases.Enfin l'azote (N2) libéré dans le milieu est inerte et sans impact dans le milieu réactionnel.Dans une seconde partie, intitulée « Synthèse des biaryles symétriques à partir des aryllithiens, en présence d'un catalyseur au fer », nous avons décrit un nouveau système catalytique au fer, permettant la synthèse directe de dérivés biaryliques symétriques à partir d'arylithiens générés in situ et d'halogénures d'aryles, dans des conditions de températures très douces en utilisant un système catalytique au fer, en absence de ligands. La procédure, qui se déroule via l'échange quantitatif in situ d'halogénure d'aryle avec les alkyllithiums, permet un excellent contrôle de la réactivité et de la sélectivité.Enfin, dans une dernière partie intitulée « Synthèse directe des biarylméthanes sans un métal de transition », nous avons mis en évidence une nouvelle méthode de synthèse de biarylméthanes dissymétriques par couplage en milieu super basique de cétones benzyliques énolisables avec des dérivés aromatiques iodés. Dans ces conditions, la présence d'un catalyseur métallique n'est plus nécessaire pour obtenir ces molécules qui présentent un fort intérêt dans le domaine pharmaceutique et dans celui des matériauxThis thesis is part of a very general search for new synthetic eco-friendly methods.In the first part, entitled "Arylation catalyzed by copper nitrate salts aryldiazonium heterocycles", we present our work describing the first example of a Sandmeyer reaction type allowing the formation of a carbon-nitrogen bond (C-N). Our systems can, indeed, arylate nitrogen nucleophiles, essentially pyrazole, from aryldiazoniums electrophiles. The patterns obtained, the arylpyrazoles, are extremely common in the field of life and also in materials. The experimental procedures we use are extremely mild, as they involve only catalytic amounts of copper and acetic acid. Furthermore, this system operates at room temperature without the presence of ligand, base or additive. As a side product of the reaction, nitrogen (N2) is released into the medium but without impacting on the inert atmosphere of the reaction. In the second part, entitled "Synthesis of symmetrical biaryls from aryllithiens in the presence of an iron catalyst", we describe a new iron catalytic system that allows the direct synthesis of symmetrical biaryl derivatives from arylithiens, generated in situ from aryl halides under very mild temperature conditions, using an iron catalyst system in the absence of ligands. The procedure which takes place via an in situ quantitatively generated aryl halide with alkyllithiums exchange, provides an excellent control of reactivity and selectivity.Finally, in the last section entitled "Direct Synthesis of biarylmethanes without a transition metal", we demonstrate a new method for the synthesis of unsymmetrical biarylmethanes in a super basic medium of benzyl ketones, with enolizable iodinated aromatic compounds. Under these conditions, the presence of a metal catalyst is not necessary. The molecules obtained have a strong interest in the pharmaceutical field and in materials
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Brittain, William David George. "Asymmetric synthesis 1,2,3-triazoles utilising the copper-catalysed azide-alkyne cycloaddition." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8143/.
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The copper-catalysed azide-alkyne cycloaddition (CuAAC) is a highly efficient reaction and is the cornerstone of “click” chemistry. However, unlike many common metal-mediated transformations asymmetric CuAAC variants are relatively sparse. This thesis details asymmetric “click” reactions with Chapter 1 introducing the CuAAC and the asymmetric variants already present in the literature. Chapter 2 outlines research demonstrating the first example of kinetic resolution of an alkyne via a CuAAC reaction. Selectivity factors of up to 22.1 ± 0.5 were obtained and triazoles and alkynes were obtained in ≤ 80% enantiomeric excess (ee). This chapter also contains a study on the simultaneous kinetic resolution of azides and alkynes; azides were obtained in >30% \(e\)\(e\), alkynes in >40% \(e\)\(e\) and a triazolic diastereomeric product was obtained in up to 90% \(e\)\(e\). In Chapter 3 the Bull-James three-component boronic acid assembly is successfully employed for the kinetic resolution of primary amine alkynes with selectivity factors of up to 4.1 obtained. The principle behind the assembly is also elaborated upon in this chapter leading to its use in both dynamic combinatorial chemistry and as a pedagogical tool. Chapter 4 details work on atropisomerism in triazolic systems. A series of novel triazoles, iodotriazoles and triazolium salts were successfully synthesised and their atropisomeric stability probed. Chapter 5 presents feasibility studies towards the asymmetric synthesis of 5,5’-bis(triazoles) and ruthenium olefin metathesis catalysts in the formation of 1,5-triazoles.
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Gorman, Ryan. "Copper-catalysed synthesis of 5- and 6-membered nitrogen-containing heterocycles." Thesis, University of York, 2016. http://etheses.whiterose.ac.uk/16167/.
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Nitrogen-containing heterocycles are an important structural motif, prevalent in both nature and medicine. N-Heterocycles can be found at the core of numerous biologically active molecules resulting in a huge amount of attention focussed on the novel synthesis of these privileged motifs from both academic and industrial researchers alike. In recent years the importance of developing efficient, “green” and cost effective routes to medicinal agents has become increasingly at the forefront of modern research. In 2009 the Taylor group reported the successful synthesis of oxindole heterocycles via a copper(II)-mediated approach. Following on from this research, the development of a high-yielding and green set of conditions is described for the synthesis of oxindoles (I). The successful application of these conditions to both 5-membered N-heterocycles (Chapter 2) and 6-membered N-heterocycles (Chapter 3) is described including thio-oxindoles (II), 3,4-dihydroquinolin-2(1H)-ones (III) and 2-quinolinones (IV). Reported, is the application of this methodology to biologically active molecules, including formal synthesis of the oxindole-containing drug Satavaptan (V) (Chapter 2.2), the first reported total synthesis of two biologically active, 3,4-dihydroquinolin-2(1H)-one containing natural products (VI and VII) (Chapter 3.7) and efforts towards the total synthesis of the 2-quinolinone-containing drug candidate HOFQ (VIII) (Chapter 3.8).
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Foltz-César, Carole. "Trisoxazolines : Synthesis and application in enantioselective palladium- and copper-catalysed reactions." Strasbourg 1, 2007. https://publication-theses.unistra.fr/public/theses_doctorat/2007/FOLTZ-CESAR_Carole_2007.pdf.
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Le but de ce travail a été de concevoir de nouveaux ligands trisoxazolines de haute symétrie et de déterminer leur intérêt par rapport aux ligands de symétrie C2 bien établis dans la littérature. Une étude directe de l’influence de la symétrie C3 en catalyse asymétrique par comparaison directe entre des systèmes trisoxazoline/métal et bisoxazoline/métal a donc été effectuée. Dans un premier temps, trois nouvelles trisoxazolines de symétrie C3 ont été synthétisées avec, sur les cycles oxazoline, les substituants chiraux phenyl, benzyl et indanyl. Des bisoxazolines et trisoxazolines à groupements mixtes ont également été obtenues. Il a été démontré que les 2-bromooxazolines, intermédiaires clé de la synthèse des trisox, se réarrangent thermiquement pour donner les dérivés a-bromo-isocyanate correspondants. Ces derniers, après réaction avec la phenylethylamine, génèrent sélectivement des aziridines, produits de N-cyclisation, ou des aminooxazolines, produits de O-cyclisation, selon les conditions réactionnelles employées. La chimie de coordination des trisoxazolines avec le palladium a ensuite été explorée. Des complexes de palladium(II) et de palladium(0) ont été synthétisés. Il a été montré que ces ligands présentent un mode de coordination bidentate en phase solide. En solution, le processus dynamique de ces complexes a été observé et des paramètres d’activation de l’échange fluxionnel du ligand ont pu être déterminés. Une comparaison directe de l’activité et de la sélectivité en catalyse d’alkylation allylique entre quatre couples différents trisoxazoline/bisoxazoline qui se distinguent par le substituant présent sur l’hétérocycle a été effectuée. Il a été constaté que les systèmes tripode/palladium induisent une meilleure énantiosélectivité et sélectivité comparés à leurs analogues bisoxazoline/palladium. Ces dernières observations ont été confirmées avec l’étude de systèmes comportant des bisoxazolines fonctionnalisées avec un bras coordinant. Enfin, la coordination dynamique des trisoxazolines au cuivre(II) a été exploitée dans deux catalyses au cuivre(II). Il a été montré que les trisoxazolines de symétrie C3 associées au cuivre forment des complexes acides de Lewis très efficaces basés le concept d’hémilabité du cuivre(II). Une application de ces catalyseurs en réaction de Mannich et d’a-amination asymétriques a montré qu’un ligand tridentate, limitant la labilité, combiné à la symétrie C3, limitant le nombre d’espèces actives possibles, aboutit donc à un système catalytique supérieur aux systèmes contenant les bisoxazolines correspondantesThis thesis describes the coordination chemistry and catalytic applications of the 1,1,1-tris(oxazolinyl)ethane (“trisox”) family of ligands. The studies described herein are primarily concerned with the effect of the threefold rotational symmetry of the ligands, as well as the role of the third oxazoline arm in catalytic reactions in which there are intermediates that possess a bidentate coordination of the trisox ligand. The syntheses of highly symmetrical chiral 1,1,1-tris(oxazolinyl)ethane ligands bearing phenyl, benzyl or indanyl substituents, and of mixed bis- and trisoxazolines is described. The isomerisation of the 2-bromooxazolines was observed, in which the thermally induced rearrangement generates the corresponding α-bromo-isocyanate derivatives. Reaction of the latter with phenylethylamine led selectively to the N-cyclised aziridines or to the O-cyclised 2-aminooxazolines, depending on the reaction conditions. The coordination chemistry of the trisoxazoline ligands with palladium is then described. Palladium(II) chloride and allyl complexes and a number of palladium(0) complexes were successfully synthesised. The dynamic behaviour of these complexes in solution was studied and activation parameters were determined for the exchange of the oxazoline moieties. The systematic comparison of the catalytic efficiency of trisox- and bisox-palladium systems in allylic substitution is described. It was demonstrated that the trisoxazoline-based complexes are superior catalysts in direct comparison to the corresponding bisoxazoline-based catalysts. The study showed that the additional donor function appears to play a role in the product/substrate exchange step as well as in the initial generation of the active catalyst. Finally, the exploitation of the dynamic coordination of the trisoxazolines to copper(II) in two copper-catalysed asymmetric reactions is described. It has been shown that C3-symmetric trisoxazolines form highly efficient enantioselective copper(II) Lewis acid catalysts, in which their success is based on the concept of a stereoelectronic hemilability of the divalent copper. In a direct comparison with the analogous bisoxazoline systems, the trisox/copper catalysts have proven to be more efficient in an enantioselective Mannich reaction as well as an enantioselective a-amination of prochiral b-ketoesters in presence of low catalyst loadings. To conclude the implications of the use of chiral tridentate podands in stereoselective catalysis compared to the more established bidentate chelates have been highlighted
Diese Arbeit beschreibt die Koordinationschemie und die katalytische Anwendung der Familie der 1,1,1-Tris(oxazalinyl)-ethanliganden („Trisox“). Die hier beschriebenen Untersuchungen behandeln in erster Linie den Einfluß der dreizähligen Rotationssymmetrie der Liganden sowie die Rolle des dritten Oxazolinarms in katalytischen Reaktionen, deren Intermediate einen bidentaten Koordinationsmodus des Trisoxliganden beinhalten. Zu Beginn wird die Synthese hochsymmetrischer chiraler 1,1,1-Tris- (oxazalinyl)ethanliganden, die Phenyl-, Benzyl- oder Indanylsubstituenten tragen, sowie nichtsymmetrischer Bis- und Trisoxazoline beschrieben, die gemischte Substituenten an der 4-Position des Oxazolins tragen. Bei den bromierten Monooxazolin-Zwischenstufen wurde eine Isomerisierung beobachtet, bei der durch thermisch induzierte Umlagerung aus den 2-Bromoxazolinen die korrespondierenden a-Bromo-isocyanat-Derivate entstehen. Diese reagieren mit Phenylethylamin in Abhängigkeit von den Reaktionsbedingungen selektiv entweder zu den N-zyklisierten Aziridinen oder den O-zyklisierten 2-Aminooxazolinen. Anschließend wird die Koordinationschemie der Trisoxazolinliganden mit Palladium beschrieben. Es konnten erfolgreich Palladium(II)chlorid- und -allyl-Komplexe und Palladium(0)-Komplexe synthetisiert werden. Im Zuge der Untersuchung des dynamischen Verhaltens dieser Komplexe in Lösung wurden die Aktivierungsparameter des Austauschs der Oxazolinreste bestimmt. Ein sys-tematischer Vergleich der katalytischen Effizienz von Trisoxund Bisox-Palladium-Systemen zeigte, daß die Trisox-basierten Komplexe den jeweils korrespondierenden Bisox-Systemen überlegen sind. Die zusätzliche Donorfunktion des dritten Oxazolinarms scheint eine wichtige Rolle beim Produkt-Substrat-Austausch und der Bildung der aktiven Katalysatorspezies zu spielen. Abschließend werden zwei kupferkatalysierte Katalysen beschrieben, bei denen die dynamische Koordination der Trisoxazoline an Kupfer(II) ausgenutzt wird. Es konnte gezeigt werden, daß C3-symmetrische Trisoxazoline hocheffiziente Kupfer(II)-Komplexe für die enantioselektive Lewissäurekatalyse bilden, deren Aktivität auf der Hemilabilität des divalenten Kupfers basiert. Im direkten Vergleich mit den analogen Bisoxazolinsystemen erwiesen sich die Trisox/Kupfer-Katalysatoren insbesondere bei niedrigen Katalysatorbeladungen als effizienter in der enantioselektiven Mannich-Reaktion und der enantioselektiven a-Aminierung prochiraler b-Ketoester. Zusätzlich wurden die Auswirkungen der Nutzung chiraler tridentater Podanden im Vergleich zu den besser etablierten bidentaten Bisox-Chelatliganden untersucht
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Foltz-Cesar, Carole. "Trisoxazolines: synthesis and application in enantioselective palladium- and copper-catalysed reactions." [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:16-opus-79452.
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Van, Der Waals Dominic. "Atom economical and environmentally benign metal catalysed synthesis." Thesis, University of Bath, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.636541.
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The use of inexpensive metal catalysts for a range of acylation reactions including the activation of anhydrides and the aminolysis of esters. Discussion on the use of a heterogeneous copper catalyst for teh reduction of a range of organic functional groups and its use in amination of nitriles.
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Male, Henry Peter John. "Towards the development, application and understanding of copper-catalysed alkene functionalisation processes using iodonium salts." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/273476.
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This thesis comprises three projects focused on the use of the combination of catalytic copper and iodonium salts towards the functionalisation of alkenes. Chapter 2 details the development of an enantioselective and regiodivergent allylic amide arylation procedure using a specific copper(II)-bisoxazoline pre-catalyst and hexafluorophosphate diaryliodonium salts. The regioselectivity of the process was discovered to be controlled by the electronic properties of the iodane employed, allowing enamide production to be biased with electron-poor iodonium salts and oxazines to be produced with electron-rich analogues. An overall scope of 38 compounds was collaboratively elaborated, with 20 synthesised personally. All products were generated in useful yields and high levels of enantioselectivity. Chapter 3 describes efforts towards the application of a copper-catalysed oxy-alkenylation procedure to the production of the macrolidal natural product (-)-lyngbyaloside B. It is proposed that an elaborate homoallylic carbamate may be coupled with a complex polyoxygenated alkenyl(aryl)iodonium salt as a fragment coupling for polyketide synthesis. Following extensive investigations, it was discovered that the challenging vinyl-iodonium salt could be synthesised in good yields and then coupled with the desired homoallylic carbamate, albeit in limited yield and low d.r. Chapter 4 presents initial studies towards a computational understanding of the copper-catalysed arylation of alkenes with iodonium salts. Evidence is presented to suggest that two functionalisation modes are energetically accessible, allowing the production of regioisomeric arylated products.
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Muldowney, Mark Patrick. "Mechanistic and synthetic studies of copper catalysed aziridination of alkenes." Thesis, University of Newcastle Upon Tyne, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297570.
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Welker, Matthias J. H. "Development and synthetic applications of asymmetric copper-catalysed conjugate addition reactions." Thesis, University of Nottingham, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.537676.
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Baboo, Sabyasachi. "Nuclear translation." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:5266f049-d576-44fd-ab26-11cf7a27f678.
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In bacteria, protein synthesis can occur tightly coupled to transcription. In eukaryotes, it is believed that translation occurs solely in the cytoplasm; I test whether some occurs in nuclei and find: (1) L-azidohomoalanine (Aha) – a methionine analogue (detected by microscopy after attaching a fluorescent tag using ‘click’ chemistry) – is incorporated within 5 s into nuclei in a process sensitive to the translation inhibitor, anisomycin. (2) Puromycin – another inhibitor that end-labels nascent peptides (detected by immuno-fluorescence) – is similarly incorporated in a manner sensitive to a transcriptional inhibitor. (3) CD2 – a non-nuclear protein – is found in nuclei close to the nascent RNA that encodes it (detected by combining indirect immuno-labelling with RNA fluorescence in situ hybridization using intronic probes); faulty (nascent) RNA is destroyed by a quality-control mechanism sensitive to translational inhibitors. I conclude that substantial translation occurs in the nucleus, with some being closely coupled to transcription and the associated proof-reading. Moreover, most peptides made in both the nucleus and cytoplasm are degraded soon after they are made with half-lives of about one minute. I also collaborated on two additional projects: the purification of mega-complexes (transcription ‘factories’) containing RNA polymerases I, II, or III (I used immuno-fluorescence to confirm that each contained the expected constituents), and the demonstration that some ‘factories’ specialize in transcribing genes responding to tumour necrosis factor α – a cytokine that signals through NFκB (I used RNA fluorescence in situ hybridization coupled with immuno-labelling to show active NFκB is found in factories transcribing responsive genes).
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Hodgkinson, Roy. "Synthesis of indoles and azaindoles via copper/palladium catalysed tandem C-N bond coupling." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504479.
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Nikolaidi, B. "First principles investigation of nanoscale processes involved in the copper-catalysed synthesis of methanol." Thesis, University of Manchester, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.505815.
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This treatise is based on first-principles of the nano-scale properties of methanol synthesis on copper. We implement calculations using density functional theory within the framework of general gradient approximation. Initially, we gain insights into the mechanism of hydrogen dissociative adsorption on Cu(100) and find that the process is activated and the transition state involves an extended H... H bond. Hydrogens adsorb preferentially at surface hollows and upon saturation of these, penetrate lattice bulk and occupy interstitials. We proceed by monitoring the adsorption of atomic hydrogen on Cu(110) and find that the surface is likely to undergo reconstruction to (1x2) missing row Cu(110). We do not find threshold coverage for restructuring and suggest that the process initiates from zero-limit coverage. Bulk absorption is again found possible upon surface saturation. Moreover, we find that hydrogen dissolution on the reconstructed surface induces a contraction of the lattice, contrarily to the other surfaces examined. Based on this observation we add to the interpretation of experimentally observed hydrogen locking-in upon surface restructuring. Subsequently, we analyse the mechanism of carbon dioxide hydrogenation to formate. Three different possible routes are considered and the possibility of surface reconstruction taken into account. Reaction barriers are lower on the perfect structure, however results on the reconstructed surface agree better to experimental range. In all cases, transition states involve tilted formates. We also analyse the minimum energy pathway dependence on structural variables. We contribute to the understanding of the nature of interaction of several additional probable intermediates of methanol synthesis; namely dioxymethylene, formyl, formaldehyde and methoxy. The strongest bound species is dioxymethylene, closely followed by formate. We conclude that the active site of Cu(110) perfect and reconstructed surfaces are the top copper ridges in all cases examined. We explain the stabilisation of the adsorbents in terms of charge transfer from the top copper atoms to the bonding atoms of the species. Finally, we examine two different possible pathways to methanol synthesis from carbon dioxide and hydrogen. We consider seven different step reactions on each route. We infer that the most probable path involves dioxymethylene and that formyl is not likely to be a precursor to methanol. Based on our calculation of activation energies, we propose that the ratelimiting step is the hydrogenation of formate to dioxymethylene.
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Fabre, Indira. "Experimental and theoretical mechanistic studies of transition-metal free and copper-catalyzed reactions." Thesis, Paris Sciences et Lettres (ComUE), 2017. http://www.theses.fr/2017PSLEE033/document.
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Cette thèse présente des travaux de méthodologie de synthèse et des études mécanistiques. Une approche complémentaire est utilisée, avec des résultats expérimentaux et des résultats théoriques issus de calculs DFT. Trois réactions ont été étudiées. La première réaction est l’alpha-arylation de cétones énolisables en l’absence de métal de transition. Elle se déroule en présence de DMF et de tBuOK. L’étude mécanistique met en évidence la formation d’une espèce riche en électrons par déprotonation du solvant. La deuxième réaction étudiée est la N-arylation de pyrazoles via la formation d’aryldiazoniums in situ. Cette réaction est catalysée au cuivre. Une évaluation de la méthode DFT la plus adaptée est présentée. Un double cycle catalytique est proposé, faisant intervenir le complexe de cuivre et l’acide acétique. La dernière réaction étudiée est la formation stéréoselective d’alkényl thioethers fluorés trisubstitués par catalyse au cuivre. La méthodologie de synthèse est présentée, suivie d’une étude mécanistique. Celle-ci révèle un mécanisme radicalaire qui peut être généralisé à d’autres substratsIn this thesis, synthetic methodology development and mechanistic studies are presented. A complementary approach, using both experiments and theoretical outcomes from DFT, is used. Three reactions were studied. The first reaction is the transition-metal free alpha-arylation of enolizable ketones. It proceeds using DMF and tBuOK. The mechanistic study reveals the formation of an electron-rich species by deprotonation of the solvent. The second reaction studied is the copper-catalyzed N-arylation of pyrazoles with arenediazonium salts generated in situ. A benchmark is performed to evaluate the best DFT methodology. A double catalytic cycle is proposed, involving copper and acetic acid. The last reaction studied is the copper-catalyzed stereoselective access to trisubstituted fluorinated alkenyl thioethers. The development of the methodology is presented. Then a mechanistic study reveals a radical mechanism that can be generalized to other substrates
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Wang, Yi. "Stereoselective synthesis of multisubstituted alkenes via ring opening reactions of cyclopropenes : enantioselective copper catalysed asymmetric reduction of alkenylheteroarenes." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4607.
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A catalytic organometallic addition-ring opening sequence of cyclopropenes that enables the efficient and highly stereoselective synthesis of multisubstituted alkenes has been developed. A possible mechanism of organoaluminium reaction is proposed. The metalloenolate resulting from ring opening can be trapped with various electrophiles, enabling a rapid increase in molecular complexity in a one-pot operation. Also, in the presence of stoichiometric magnesium halides, a range of bis-activated cyclopropenes undergo highly stereoselective ring-opening reactions to produce multisubstituted alkenyl halides. The halogen nucleophile promotes Lewis-acid mediated regioselective SNVσ attack at the sp2-carbon of cyclopropene, resulting in the formation of acyclic conjugate enolate, which can be trapped with enones to furnish more highly functionalised products. At last, copper-catalysed asymmetric conjugate reductions of β,β'-disubstituted 2-alkenylheteroarenes are reported. A range of nitrogen-containing aromatic heterocycles are able to provide effective activation of an adjacent alkene for highly enantioselective catalytic conjugate reduction reactions. Extension of the general concept to other classes of heteroarenes has been proven successful. Further manipulation of the condition is required to tolerate more hindered heteroarene substrates.