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Dissertations / Theses on the topic 'Hydroamination'

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Published: 4 June 2021
Last updated: 22 June 2024

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1

Shasha, Adelle. "Metal-Catalysed Hydroamination." Science. School of Chemistry, 2007. http://hdl.handle.net/2123/1710.

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Doctor of Philosophy(PhD),
This thesis describes the synthesis of terminal and internal amino and amidoalkynes and their hydroamination (cyclisation) catalysed by the complex (bis(N-methylimidazol-2-yl)methane)dicarbonylrhodium(I) tetraphenylborate (1). A series of analogous palladium complexes were also prepared and investigated for catalytic hydroamination. The scope of the rhodium(I) complex (1) for the intramolecular hydroamination of more complex amino and amidoalkyne substrates was investigated. This was made possible with the synthesis of aliphatic substrates, namely, 4 pentyn 1 amide (3) and 5 hexyn 1 amide (4) and a number of aromatic substrates, namely, 1, 4 diamino-2, 5 diethynylbenzene (5), 1, 4-diamino-2, 5 bis(phenylethynyl)benzene (6), 2, 3-diamino-1, 4-diethynylbenzene (7), 2, 3-diamino-1, 4-bis(phenylethynyl)benzene (8), 1, 5-bis(acetamido)-2, 4-diethynylbenzene (9), N-(acetyl)-2-ethynylbenzylamine (10) and N-(acetyl)-2-(phenylethynyl)benzylamine (11). The rhodium(I) complex (1) catalytically cyclised the aliphatic 4 pentyn 1 amide (3) regioselectively to the 6 membered ring, 3, 4 dihydro 2 pyridone (64) as the sole product. Attempts to cyclise 5 hexyn 1 amide (4) to produce either the 6 or 7 membered ring were unsuccessful. Compounds 5, 6, 7 and 8 were doubly cyclised to 1, 5 dihydro pyrrolo[2, 3 f]indole (71), 1, 5-dihydro-2, 6-diphenyl-pyrrolo[2, 3 f]indole (73), 1, 8-dihydro-pyrrolo[2, 3 g]indole (74) and 1, 8-dihydro-2, 7-diphenyl-pyrrolo[2, 3 g]indole (75) respectively. The aromatic amides with terminal acetylenes 9 and 10 cyclised to give 1, 7 diacetyl pyrrolo[3, 2 f]indole (76) and N (acetyl) 1, 2 dihydroisoquinoline (77) respectively. However, attempts to cyclise 11 were unsuccessful. Thus the rhodium(I) complex (1) successfully catalysed via hydroamination both terminal and internal acetylenic amine and amide substrates, to give pyridones, indoles and isoquinolines. Cationic and neutral palladium complexes incorporating the bidentate heterocyclic nitrogen donor ligand bis(N-methylimidazol-2-yl)methane (bim; 2) were synthesised: [Pd(bim)Cl2] (15), [Pd(bim)2][BF4]2 (17) [Pd(bim)(Cl)(CH3)] (14), [Pd(bim)(CH3)(NCCH3)][BF4] (16). All of the complexes were active as catalysts for the intramolecular hydroamination reaction, using the cyclisation of 4 pentyn 1 amine (21) to 2 methyl 1 pyrroline (22) as the model test reaction. Percentage conversions, turnover numbers and reaction profiles for each complex were compared to the rhodium(I) complex (1). These studies have shown that the catalytic activity was not significantly dependent on the bim donor ligand or the choice of metal. Substitution of the bim (2) ligand with the COD ligand and the use of methanol as the solvent did impact significantly on the efficiency of the hydroamination reactions.
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2

Shasha, Adelle. "Metal-Catalysed Hydroamination." Thesis, The University of Sydney, 2006. http://hdl.handle.net/2123/1710.

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This thesis describes the synthesis of terminal and internal amino and amidoalkynes and their hydroamination (cyclisation) catalysed by the complex (bis(N-methylimidazol-2-yl)methane)dicarbonylrhodium(I) tetraphenylborate (1). A series of analogous palladium complexes were also prepared and investigated for catalytic hydroamination. The scope of the rhodium(I) complex (1) for the intramolecular hydroamination of more complex amino and amidoalkyne substrates was investigated. This was made possible with the synthesis of aliphatic substrates, namely, 4 pentyn 1 amide (3) and 5 hexyn 1 amide (4) and a number of aromatic substrates, namely, 1, 4 diamino-2, 5 diethynylbenzene (5), 1, 4-diamino-2, 5 bis(phenylethynyl)benzene (6), 2, 3-diamino-1, 4-diethynylbenzene (7), 2, 3-diamino-1, 4-bis(phenylethynyl)benzene (8), 1, 5-bis(acetamido)-2, 4-diethynylbenzene (9), N-(acetyl)-2-ethynylbenzylamine (10) and N-(acetyl)-2-(phenylethynyl)benzylamine (11). The rhodium(I) complex (1) catalytically cyclised the aliphatic 4 pentyn 1 amide (3) regioselectively to the 6 membered ring, 3, 4 dihydro 2 pyridone (64) as the sole product. Attempts to cyclise 5 hexyn 1 amide (4) to produce either the 6 or 7 membered ring were unsuccessful. Compounds 5, 6, 7 and 8 were doubly cyclised to 1, 5 dihydro pyrrolo[2, 3 f]indole (71), 1, 5-dihydro-2, 6-diphenyl-pyrrolo[2, 3 f]indole (73), 1, 8-dihydro-pyrrolo[2, 3 g]indole (74) and 1, 8-dihydro-2, 7-diphenyl-pyrrolo[2, 3 g]indole (75) respectively. The aromatic amides with terminal acetylenes 9 and 10 cyclised to give 1, 7 diacetyl pyrrolo[3, 2 f]indole (76) and N (acetyl) 1, 2 dihydroisoquinoline (77) respectively. However, attempts to cyclise 11 were unsuccessful. Thus the rhodium(I) complex (1) successfully catalysed via hydroamination both terminal and internal acetylenic amine and amide substrates, to give pyridones, indoles and isoquinolines. Cationic and neutral palladium complexes incorporating the bidentate heterocyclic nitrogen donor ligand bis(N-methylimidazol-2-yl)methane (bim; 2) were synthesised: [Pd(bim)Cl2] (15), [Pd(bim)2][BF4]2 (17) [Pd(bim)(Cl)(CH3)] (14), [Pd(bim)(CH3)(NCCH3)][BF4] (16). All of the complexes were active as catalysts for the intramolecular hydroamination reaction, using the cyclisation of 4 pentyn 1 amine (21) to 2 methyl 1 pyrroline (22) as the model test reaction. Percentage conversions, turnover numbers and reaction profiles for each complex were compared to the rhodium(I) complex (1). These studies have shown that the catalytic activity was not significantly dependent on the bim donor ligand or the choice of metal. Substitution of the bim (2) ligand with the COD ligand and the use of methanol as the solvent did impact significantly on the efficiency of the hydroamination reactions.
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3

Penzien, Jochen. "New heterogeneous catalysts for hydroamination reactions." [S.l. : s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=964639076.

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4

Jiménez, Silva Oriol. "Novel heterogeneous catalysts for intermolecular hydroamination reactions." [S.l.] : [s.n.], 2006. http://mediatum2.ub.tum.de/doc/601479/document.pdf.

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5

Couce, Ríos Almudena. "Mechanistic insights into metal-catalyzed hydroamination reactions." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/403762.

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El tema de esta tesis es el estudio DFT del mecanismo de hidroaminaciones intermoleculares catalizadas por catalizadores de rodio y oro. Los compuestos que contienen nitrógeno son muy valiosos y tienen muchos usos que van desde productos farmacéuticos hasta productos químicos. La reacción de hidroaminación es la vía más económica para sintetizar aminas sustituidas. Los catalizadores metálicos que han sido desarrollados para la hidroaminación directa incluyen tanto lantánidos como metales de transición tempranos y tardíos. Los catalizadores más versátiles para la hidroaminación intermolecular se basan en metales de transición tardíos. Hay muchos estudios publicados en los últimos años acerca de esta reacción, pero a pesar del esfuerzo algunas preguntas permanecen abiertas. Los principales retos de las reacciones de hidroaminación son el uso de aminas simples y sustratos inactivados, la versión intermolecular, el control de la regioselectividad (especialmente la versión anti-Markovnikov) y la versión asimétrica. En esta tesis nos hemos centrado principalmente en el estudio del control de la regioselectividad en la versión intermolecular de esta reacción y en un proceso asimétrico. El primer y segundo capítulo son una introducción al tema y una explicación teórica de todos los temas utilizados en esta tesis. En el tercer capítulo se recogen los puntos que este trabajo pretende lograr, en el cuarto capítulo se estudió una reacción de hidroaminación anti-Markovnikov de alquenos catalizada por un catalizador de rodio desarrollado por Hartwig et al. El quinto capítulo trata de la reacción de hidroaminación enantioselectiva de alenos catalizados por un catalizador de rodio. El sistema desarrollado por Breit y compañeros ha sido elegido para nuestro estudio. El sexto capítulo está dedicado a la reacción de hidroaminación de alquinos, alquenos y alenos con hidracina catalizada por tres catalizadores catiónicos de oro diferentes desarrollados por los grupos de Bertrand y Hasmi. En el séptimo capítulo estudiamos una reacción de hidroaminación anti-Markovnikov catalizada por oro. El sistema de Widenhoefer ha sido seleccionado ya que es el único ejemplo presente en la literatura. El último capítulo de esta tesis incluye una breve conclusión y un resumen del resultado del trabajo realizado.
The topic of this thesis is the DFT study of the mechanism of intermolecular hydroaminations catalyzed by rhodium and gold catalyst. The nitrogen-containing compounds are very valuable and have a lot of uses ranging from pharmaceutical to chemical. The hydroamination reaction is the most economical pathway to synthesize substituted amines. Metal catalysts developed for direct hydroamination includes lanthanides, as well as early and late transition metals. The most versatile catalysts for the intermolecular hydroamination are based on late transition metals. There are a lot of studies published in recent years about this reaction, but despite the effort some questions remain open. The main challenges of hydroamination reactions are the use of simple amines and unactivated substrates, the intermolecular version, the control of regioselectivity (especially the anti-Markovnikov version) and the asymmetrical version. In this thesis we mainly focused on the study of the control of regioselectivity in the intermolecular version of this reaction and an asymmetric process. The first and second chapters are an introduction to the subject and a theoretical explanation of all the topics used in this thesis. In the third chapter are collected the points this work pretends to achieve, in the fourth chapter we studied an anti-Markovnikov hydroamination of alkenes catalyzed by a rhodium catalyst developed by Hartwig et al. The fifth chapter deals with the enantioselective hydroamination of allenes catalyzed by a rhodium catalyst. The system developed by Breit and coworkers has been chosen for our study. The sixth chapter is devoted to the hydroamination reaction of alkynes, alkenes and allenes with hydrazine catalyzed by three different cationic gold catalysts developed by Bertrand and Hasmi’s groups. In the seventh chapter we studied an Au-catalyzed anti-Markovnikov hydroamination. The Widenhoefer system has been selected since is the only example in the literature. The last chapter of this thesis includes a brief conclusion and summary of the outcome of the work carried out.
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6

Shanbhag, G. V. "Studies on hydroamination reactions using heterogeneous catalysts." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2008. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/2626.

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7

Abadie, Marc-Antoine. "Hydroamination intramoléculaire asymétrique d'alcènes catalysée à l'or." Thesis, Lille 1, 2014. http://www.theses.fr/2014LIL10065/document.

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La catalyse de la réaction d'hydroamination intramoléculaire asymétrique d'aminoalcènes a été étudiée en utilisant différents complexes d'Au(I) et (III) activés par un sel d'argent. Parmi les ligands phosphorés et diaminocarbènes testés, les complexes mononucléaires d'Au(I) composés de ligands phosphoramidites dérivés du BINOL ont d'abord présenté les meilleurs résultats. Ces ligands ont été améliorés par l'addition de substituants stériquement encombrants sur le fragment BINOL. L'utilisation de ces ligands pour la catalyse à l'Au(I) de l'hydroamination asymétrique des aminoalcènes a donné de bonnes conversions et des excès énantiomériques notables à température ambiante. Par la suite, des complexes binucléaires d'Au(I) ont aussi été étudiés comme catalyseurs pour la réaction d'hydroamination intramoléculaire asymétrique d'aminoalcènes. Un complexe binucléaire d'Au(I) basé sur une diphosphine sélectionnée et combiné à un sel d'argent a permis d'obtenir de bonnes conversions et énantiosélectivités à température ambiante et en présence d'eau. Les deux énantiomères du produit de réaction ont pu être obtenus en contrôlant les paires d'ions du catalyseur via la polarité du solvant de réaction employé. Le complexe actif a été caractérisé à l'état solide par diffraction des rayons X et en solution par RMN DOSY 1H. Aucun atome d'argent ne prend part au mode de coordination de ce complexe
The intramolecular gold catalyzed asymmetric hydroamination of alkenes was studied screening a series of mononuclear gold(I) and (III) complexes in combination with silver salts. Among the various chiral phosphine and diaminocarbene ligands tried, the best catalysts arose from mononuclear gold(I) complexes synthesized from BINOL based phosphoramidite ligands. The latest were improved by addition of bulky substituents at specific positions of the BINOL scaffold. The resulting gold(I) complexes were combined with selected silver salts to afford efficient catalysts for intramolecular hydroamination of alkenes at mild temperatures, with good conversions and average enantioselectivities. Afterwards binuclear gold(I) complexes were investigated as catalysts for the intramolecular asymmetric hydroamination of alkenes. When combined to a silver salt, selected diphosphine binuclear gold(I) chloride complex afforded chiral amines for the first time in high conversions and enantioselectivities, within mild conditions and the presence of water. Both enantiomers of the products could be obtained by controlling the molecular ion-pairs through the solvent polarity. The gold(I) cationic active species was characterized for the first time unambiguously at the solid state by X-ray analysis and in solution by DOSY 1H NMR experiments. No contribution of silver chloride was observed on the bonding mode of the catalyst
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8

Abadie, Marc-Antoine. "Hydroamination intramoléculaire asymétrique d'alcènes catalysée à l'or." Electronic Thesis or Diss., Lille 1, 2014. http://www.theses.fr/2014LIL10065.

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La catalyse de la réaction d'hydroamination intramoléculaire asymétrique d'aminoalcènes a été étudiée en utilisant différents complexes d'Au(I) et (III) activés par un sel d'argent. Parmi les ligands phosphorés et diaminocarbènes testés, les complexes mononucléaires d'Au(I) composés de ligands phosphoramidites dérivés du BINOL ont d'abord présenté les meilleurs résultats. Ces ligands ont été améliorés par l'addition de substituants stériquement encombrants sur le fragment BINOL. L'utilisation de ces ligands pour la catalyse à l'Au(I) de l'hydroamination asymétrique des aminoalcènes a donné de bonnes conversions et des excès énantiomériques notables à température ambiante. Par la suite, des complexes binucléaires d'Au(I) ont aussi été étudiés comme catalyseurs pour la réaction d'hydroamination intramoléculaire asymétrique d'aminoalcènes. Un complexe binucléaire d'Au(I) basé sur une diphosphine sélectionnée et combiné à un sel d'argent a permis d'obtenir de bonnes conversions et énantiosélectivités à température ambiante et en présence d'eau. Les deux énantiomères du produit de réaction ont pu être obtenus en contrôlant les paires d'ions du catalyseur via la polarité du solvant de réaction employé. Le complexe actif a été caractérisé à l'état solide par diffraction des rayons X et en solution par RMN DOSY 1H. Aucun atome d'argent ne prend part au mode de coordination de ce complexe
The intramolecular gold catalyzed asymmetric hydroamination of alkenes was studied screening a series of mononuclear gold(I) and (III) complexes in combination with silver salts. Among the various chiral phosphine and diaminocarbene ligands tried, the best catalysts arose from mononuclear gold(I) complexes synthesized from BINOL based phosphoramidite ligands. The latest were improved by addition of bulky substituents at specific positions of the BINOL scaffold. The resulting gold(I) complexes were combined with selected silver salts to afford efficient catalysts for intramolecular hydroamination of alkenes at mild temperatures, with good conversions and average enantioselectivities. Afterwards binuclear gold(I) complexes were investigated as catalysts for the intramolecular asymmetric hydroamination of alkenes. When combined to a silver salt, selected diphosphine binuclear gold(I) chloride complex afforded chiral amines for the first time in high conversions and enantioselectivities, within mild conditions and the presence of water. Both enantiomers of the products could be obtained by controlling the molecular ion-pairs through the solvent polarity. The gold(I) cationic active species was characterized for the first time unambiguously at the solid state by X-ray analysis and in solution by DOSY 1H NMR experiments. No contribution of silver chloride was observed on the bonding mode of the catalyst
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9

Ng, Peter J. "Directed Organocatalytic Intermolecular Cope-type Hydroamination of Alkenes." Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/19895.

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Intermolecular reactions are inherently more difficult than intramolecular reactions, and several transformations can only occur as cyclizations, often to form 5-membered rings. The use of directing or tethering groups allowing preassociation with a reagent or catalyst is a common strategy to overcome such low reactivity, which can lead to increases in the rate, regioselectivity and stereoselectivity of intermolecular reactions. Typically, such preassociation involves hydrogen bonds, coordination to a metal ion/catalyst or stepwise installation of a temporary tether. As part of ongoing investigations on metal-free hydroaminations, it was speculated that a simple organic molecule could allow the formation of a temporary tether and enable directed intermolecular Cope-type hydroaminations to proceed at room temperature. Recently, it was found that alkylhydroxylamines add to allylic amines regioselectively in the presence of an aldehyde catalyst. This thesis presents the background material, design elements, optimization and scope of this reactivity.
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10

Rizk, Toni. "Synthesis of pyridines and pyrazines using intramolecular hydroamination." Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28453.

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Despite recent progress, the scope and efficiency of intramolecular hydroamination has not yet reached its full synthetic potential. In particular, cyclizations to form 6-membered rings and applications in the synthesis of aromatic nitrogen heterocycles remain rare, despite the potential to access a variety of medicinally relevant heterocycles. The intramolecular hydroamination of alkynes presented offers a general approach to such nitrogen heterocycles from appropriately substituted acyclic precursors, in which the oxime functionality allows for a milder cyclization event and allows subsequently for the installation of one additional unsaturation (via loss of H2O). The discovery and optimization of an acid-catalyzed, hydroamination-isomerization-aromatization route for the synthesis of pyridines and pyrazines will be presented and discussed.* *Please refer to dissertation for diagrams.
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11

Wixey, James S. "Novel calcium complexes applied to intramolecular hydroamination catalysis." Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/37858/.

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This thesis discusses the synthesis, characterisation, and reactivity studies of a range of new chiral calcium complexes supported by various polydentate N-donor ligands and their suitability as catalysts for intramolecular hydroamination. Chapter One outlines the case for developing organocalcium complexes, including a general overview of their current application to a variety of heterofunctionalisation reactions. Chapter Two introduces the chiral ethylene diamines which are extensively used as calcium supporting ligands and later as precursors for the synthesis of bisimidazoline and potential imoxazoline ligands. Chapter Two provides details of the diamine synthesis and includes studies related to racemisation concerns of the chiral centre. Chapter Three discusses novel calcium complexes supported by the chiral ethylene diamine analogues presented in Chapter Two. Complex synthesis, characterisation, and catalytic performance in intramolecular hydroamination is probed and discussed. Chapter Four details a range of new bisimidazoline ligands and their employment as supporting ligands on calcium. The catalytic performance of the resulting complexes in intramolecular hydroamination is subsequently analysed and discussed. Chapter Five investigates the attempted development of a total synthetic pathway to a new class of imoxazoline ligand and related issues. Chapter Six contains all experimental procedures, characterising data pertaining to all new compounds and complexes presented in this Thesis. Appendices A-K contain additional catalytic figures and tables of crystallographic data for all new crystallographically characterised compounds. Summary sheets of every literature and new compound presented mentioned in this Thesis are also included, along with copies of both printed publications resulting from this Thesis at the time of submission.
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12

Roveda, Jean-Gregoire. "Hydrazides as tunable reagents for alkene hydroamination and aminocarbonylation." Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28355.

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Intramolecular hydroamination and aminocarbonylation of alkenes are highly desirable synthetic transformations providing access to structures frequently used in medicinal chemistry. Most research efforts currently focus on achieving this reactivity through transition metal catalysis. Our approach involves using hydrazides under thermal (metal-free) conditions to achieve hydroamination or aminocarbonylation upon selection of the appropriate hydrazide substituent (R). Upon substitution when R=Ph, various different compounds were synthesized and isolated in moderate to excellent yields (39 to 98%). Primary and secondary hydrazides pyrrolidines were cyclized and terminal or internal substituted double bonds were tolerated. Morpholine, piperazine, piperidine and azepane moieties were also cyclised with increased heat. This methodology was also consistent with hydroamination on a benzylic olefin. Aminocarbonylation products were obtained in good to excellent yields (52--86%), when R=NH2 and O-tBu. Substituted terminal bonds are obtained with retention of alkene stereochemistry, suggesting a novel concerted reaction pathway. Such reactions are very practical: the starting materials are accessed readily, and both starting materials and products are easy to handle and purify. Such products are also remarkably stable at high temperatures.* *Please refer to dissertation for diagrams.
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13

Arbour, Jannine Louise. "Metal-mediated intramolecular hydroamination and hydro(acy)alkoxylation reactions." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/9203.

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This PhD thesis describes work undertaken to effect asymmetric catalysis in hydroamination and hydro(acy)alkoxylation reactions of allenes. The introductory Chapter provides an overview of recent advances in asymmetric heterofunctionalisation reactions of allenes. This includes intra- and inter-molecular reactions involving C-N and C-O bond formations. Chapter 2 begins by comparing the preparation of a γ-allenic alcohol by two different synthetic routes and its subsequent use in intramolecular hydroalkoxylation reactions using copper(II) and silver(I) salts. From this study, the ability of silver diphosphine complexes to facilitate enantioselective hydroalkoxylation reactions in a 5-exo-trig fashion was discovered. Extensive reaction optimisation was undertaken, however only moderate ee’s and conversions were observed. In Chapter 3, the use of other metal Lewis acids to catalyse hydroalkoxylation reactions of γ-allenic alcohols is presented. DFT calculations undertaken by a colleague (Prof H. S. Rzepa) were used to rationalise the observed regioselectivities with silver(I), zinc(II), and tin(II) triflates. From DFT calculations, the metal counteranion was found to be intimately involved in the C-O bond formation. In the following two Chapters, the possibility of asymmetric synthesis by using chiral anionic ligands is discussed. In Chapter 4, additional γ-allenic alcohols and β-allenic acids were synthesised for intramolecular hydroalkoxylation or hydroacyalkoxylation reactions respectively. In Chapter 5, the respective γ-allenic amines were prepared for intramolecular hydroamination. In both cases, the outcome, scope and limitations of the reaction are discussed. In Chapter 6, an overall conclusion and future work is discussed. The last Chapter contains experimental procedures and characterisation data of all the compounds synthesised during the course of this project.
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14

Hesp, Colin R. "Stereoselective Cope-Type Hydroamination of Allylic Amines Using Simple Aldehydes as Catalysts." Thèse, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31175.

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Stereoselective hydroaminations of unactivated alkenes are rare as this represents a very challenging synthetic transformation. The most efficient examples occur in biased intramolecular systems and highly enantioselective intermolecular examples are rare, which is consistent with the forcing conditions required to catalyze the reactions. This limited reactivity also accounts for the lack of highly diastereoselective hydroamination variants. Recently our group has shown that intermolecular Cope-Type hydroamination of unactivated alkenes can be achieved using simple aldehydes as catalysts. The aldehyde promotes pre-association of the two reaction partners, inducing temporary intramolecularity resulting in a remarkably facile hydroamination event. This thesis will present the development of two reactions: intermolecular enantioselective Cope-type hydroamination and intermolecular diastereoselective Cope-type hydroamination of allylic amines.
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15

Hunt, Ashley D. "Intramolecular Cope-type Hydroamination of Alkenes and Alkynes Using Hydrazides." Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/19881.

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Nitrogen-containing molecules are ubiquitous in both natural products and pharmaceutical drugs, thus an efficient method for the formation of these motifs is of great importance. Hydroamination, that is the addition of an N-H bond across an unsaturated carbon-carbon bond of an alkene or alkyne, stands out as a potential approach to obtain such molecules. To date, most research in this area relies on transition-metal catalysis to enable such reactivity. In efforts directed towards metal-free alternatives, we have developed a simple, metal-free hydroamination of alkenes using hydrazides. Further investigation into the corresponding reactivity of alkynes with hydrazides has provided access to novel azomethine imine products. In Chapter 2, expansion of the substrate scope with respect to the intramolecular hydroamination of alkenes using hydrazides, as well as studies directed towards elucidation of the mechanism of this reaction will be presented. The intramolecular hydroamination of alkynes using hydrazides and methods to access and isolate the azomethine imine products formed will be discussed in Chapter 3.
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16

Peng, Hao. "Investigations toward metal-free hydroamination approaches to aromatic nitrogen heterocycles." Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28874.

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Metal-free hydroamination approaches were investigated to afford aromatic nitrogen heterocycles. Several substrates were synthesized to test different sequences such as 6-endo-dig and 6-exo-dig cyclization. The desired reactivity was observed for each of the desired routes, which were discussed in Chapter 2. More research is needed for optimization in the future.* *Please refer to dissertation for diagrams.
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17

Knight, Paul David. "Chiral-at-metal catalyst designs for alkene polymerisation and hydroamination." Thesis, University of Warwick, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.403123.

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18

Cheng, Xiaohui. "Transition metal catalysed homogeneous hydroamination, allylic substitution and transfer hydrogenation reactions." Thesis, King's College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410013.

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19

Philippot, Karine. "Evaluation de complexes amido de rhodium en hydroamination catalytique des oléfines." Toulouse 3, 1993. http://www.theses.fr/1993TOU30090.

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Ce memoire decrit une etude exploratoire de la reactivite de complexes amido de rhodium pour l'hydroamination catalytique d'olefines. Jusqu'ici, aucune solution satisfaisante n'a ete mise a jour pour cette reaction qui constituerait, a l'evidence, une alternative tres interessante aux procedes actuels de synthese industrielle d'amines. L'examen des differents cycles catalytiques envisageables a permis d'imaginer un processus original mettant en jeu, comme precurseur catalytique, un complexe amido de rhodium. La reaction de l'anilidure de lithium sur des complexes de rhodium (i) a ete etudiee en detail. Les complexes attendus, (pr#3)#2rhnhph, ne sont pas stables. En revanche, il a ete montre pour la premiere fois, qu'en presence d'un exces d'anilidure, il se forme des entites, stables en solution, dont la formule, (pr#3)#2rh(nhph)#2#, li#+ a ete etablie sur la base d'analyses approfondies en rmn #3#1p et #1#0#3rh. Ces systemes ont ete evalues pour l'hydroamination du norbornene par l'aniline, reaction choisie en vue d'une comparaison avec le seul systeme d'hydroamination catalytique par activation n-h connu. La reaction conduit a un melange du produit d'hydroamination et d'un produit resultant d'une reaction d'hydroarylation inattendue. L'activite catalytique depend de la nature de la phosphine liee au rhodium mais surtout de la nature du solvant. Les meilleurs resultats sont obtenus lorsque l'amine a condenser est utilisee comme solvant. Cette reaction a ete etendue, avec succes, aux toluidines et a la diphenylamine. Dans le cas du styrene, ces systemes anilido de rhodium conduisent a une amination totalement regioselective, pour former, majoritairement, l'imine phc(me)=nph. Cette formation d'imine, observee egalement dans le cas du 1-hexene, a ete rationalisee sur la base d'un mecanisme qui s'apparente au principe de base du procede wacker. Ce travail montre qu'il est possible de stabiliser des complexes anilido de rhodium et de realiser la condensation catalytique d'amines sur des olefines, sans qu'il soit necessaire d'envisager une activation n-h. De plus, il ouvre de nouvelles perspectives pour la transformation catalytique directe d'olefines en imines, reaction jusqu'ici sans precedent
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20

Higginbotham, Mari C. M. "Gold(I)-catalysed synthesis of cyclic sulfamidates by intramolecular allene hydroamination." Thesis, Heriot-Watt University, 2014. http://hdl.handle.net/10399/2789.

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The work reported in this thesis outlines the gold(I)-catalysed synthesis of cyclic sulfamidates by intramolecular allene hydroamination. Work carried out in an attempt to prepare a novel acyl anion equivalent is also included but endeavours were halted after one year of study. The thesis is divided into six chapters: Chapter one provides an introduction to the reactivity of gold, current metal-catalysed hydroamination reactions and allene structure, synthesis and reactivity. The current synthetic methods for the preparation of sulfamidates and their uses is also covered. Chapter two outlines the attempted use of the Burgess reagent to prepare olefinically substituted sulfamidates and the attempts to reverse regioselectivity in sulfamidate synthesis. Chapter three includes an initial proof of concept in gold(I) catalysis and an account of substrate synthesis. Allenes were synthesised by Crabbé homologation or Johnson- Claisen rearrangement reactions. The allenes were then converted to the corresponding sulfamates. Chapter four outlines our studies of gold(I)-catalysed hydroamination. This includes optimisation of catalyst and the effects of substitution on reaction rate and stereochemical hypothesis. The current scope and limitations of this chemistry is also discussed. Chapter five outlines the research work attempted within the first year of study. The work focussed on the attempted preparation of a thermally unmasked acyl anion equivalent. Chapter six provides a formal report of the experimental procedures. Stereochemical abstract: All compounds with stereogenic centres were prepared as racemic mixtures but only one enantiomer is represented in the schemes.
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21

Lovelock, Sarah Lousie. "The development of novel biocatalysts for the asymmetric hydroamination of alkenes." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/the-development-of-novel-biocatalysts-for-the-asymmetric-hydroamination-of-alkenes(0ee38091-0f14-436f-bd83-d0cead9b3831).html.

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The research presented in this thesis describes the application of phenylalanine ammonia lyase from the bacteria Anabaena variabilis (AvPAL), as a biocatalyst for the asymmetric hydroamination of cinnamic acid derivatives. PALs from eukaryotic sources such as the plant Petroselinum crispum (PcPAL) and yeast Rhodotorula glutinis (RgPAL) have been widely used as biocatalysts for the synthesis of non-natural amino acids. For example the PAL catalyzed hydroamination of 2’-chlorocinnamic acid has been implemented by DSM Pharma Chemicals on a tonne scale. However, there are very few examples of prokaryotic PALs and to our knowledge their activity towards unnatural substrates has not been investigated. Herein we explore the activity of AvPAL towards a panel of cinnamic acid analogues. For comparison, the activity of the commonly studied eukaryotic PcPAL and RgPAL towards the same substrate panel was also investigated. Although the difference in substrate conversions between the three PALs was fairly unremarkable, a significant reduction in product e.e was observed following prolonged reaction times with all three PALs towards substrates bearing electron deficient aromatic rings. A time dependence on e.e. has not been previously reported for ammonia lyases and all previously described biotransformations have been reported to proceed with excellent e.e. in favour of the L-enantiomer. The mechanism leading to the formation of D-phenylalanine derivatives was explored through mutagenesis of key active site residues and isotopic labeling studies. The results obtained demonstrate that D-amino acid formation occurs via a previously unobserved competing MIO-independent pathway which proceeds in a non-stereoselective manner. In addition, the observations are consistent with amino acid deamination occurring via a stepwise E1cB elimination mechanism. In order to develop a more general biocatalytic method for asymmetric hydroamination reactions, the activity of PAL towards substrates lacking the carboxylic acid functionality was investigated. The synthesis of a panel of substrates and subsequent screening with AvPAL and RgPAL is described. Unfortunately, the wild-type enzymes demonstrated no activity towards any of the substrates screened. These enzymes were also screened for their promiscuity towards the nucleophilic amine partner and although deamination activity towards N-methyl-L-phenylalanine was observed, no hydroamination activity was detected using primary amines as nucleophiles. In order to broaden the substrate specificity of PAL enzymes, a number of screening methods have been developed. Herein we present both liquid phase and colony based colorimetric screens for the detection of PAL catalyzed hydroamination activity. Furthermore these screens have been used to screen libraries of variants for increased D-selectivity and hydroamination activity towards β-methylstyrene and cinnamyl alcohol derivatives.
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22

Lepori, Clément. "Complexes de fer(II) et de cobalt(II) de basse coordinance : synthèses, caractérisations et applications en réaction d’hydroamination des alcènes." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS509.

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Les motifs azotés sont présents dans de nombreuses molécules d’intérêts pharmaceutiques. Les méthodes de synthèses traditionnelles de ces motifs vont, par exemple, de la substitution nucléophile d’amines sur des halogénures d’alkyles à de l’amination réductrice des composés carbonylés. Ces méthodes, bien qu’efficaces, nécessitent néanmoins des quantités stœchiométriques de réactifs pour être appliquées et génèrent souvent des quantités importantes de déchets. Un des challenges de la chimie organique moderne consiste à développer de nouvelles méthodes de synthèses de ces motifs plus économiques et plus respectueuses de l’environnement en produisant un taux de déchets le plus faible possible. L’addition directe d’une amine sur une double liaison carbone-carbone non-activée que l’on appelle la réaction d’hydroamination des alcènes est une approche très prometteuse pour le développement d’une méthodologie de synthèse alternative de ces composés. En effet, dans cette réaction, tous les atomes du substrat de départ sont transférés au produit réduisant ainsi considérablement les déchets produits. De plus, les amines et les oléfines employées sont des réactifs relativement bon marché, abondants et variés. Néanmoins, cette transformation a priori simple nécessite généralement l’emploi d’un catalyseur. Dans la littérature, la réaction d’hydroamination des alcènes a été étudiée en utilisant comme catalyseur des complexes de métaux alcalins, alcalino-terreux, de terre-rares et de métaux de transition. Au commencement de ce projet, il n’existait pas d’exemples de réaction d’hydroamination des alcènes mettant en jeu des amines primaires non protégées catalysée par des complexes de fer ou de de cobalt. Dans ce contexte, notre équipe s’est intéressée à la réactivité de complexes de fer(II) et de cobalt(II) de basse valence stabilisés par des ligands de type β-dicétiminate. Ces complexes se sont révélés être d’excellents catalyseurs pour promouvoir la réaction d’hydroamination des amines primaires non protégées liées à des alcènes non activés.Dans un premier temps, les synthèses des complexes de fer(II) et de cobalt(II) alkyles stabilisés par des ligands β-dicétiminates ainsi que leurs applications en réaction de cyclohydroamination des amines primaires non protégées seront présentées. De plus, des études mécanistiques poussées permettront d’éclaircir le mécanisme de la réaction, qui est proposé de passer par une étape élémentaire clé d’insertion 1,2 migratoire aboutissant à la formation d’une liaison carbone-azote.Dans un second temps, les influences des propriétés électroniques et stériques des ligands sur la réactivité en réaction d’hydroamination des alcènes des complexes de fer(II) alkyles seront étudiées. Nous nous attarderons particulièrement sur des complexes stabilisés par des ligands β-dicétiminates dissymétriques ou iminoanilidures. Les données cristallographiques des complexes à l’état solide permettront alors de rationaliser les variations de réactivités de ces différents complexes.Enfin, les complexes de fer(II) et de cobalt(II) synthétisés précédemment seront exploités pour développer de nouvelles réactivités en réactions d’oxydation, d’amination oxydante ou de création de liaison azote-silicium par un couplage déshydrogénant
The nitrogenous units are present in many molecules of pharmaceutical interest. The traditional synthesis methods of these units range, for example, from the nucleophilic substitution of amines on alkyl halides to reductive amination of the carbonyl compounds. These methods, although effective, nevertheless require stoichiometric amounts of reagents to be applied and often generate large amounts of waste. One of the challenges of modern organic chemistry is to develop new methods of synthesizing these more economical and environmentally friendly patterns by producing the lowest waste rate possible. The direct addition of an amine to an unactivated carbon-carbon double bond known as the alkene hydroamination reaction is a very promising approach for the development of an alternative synthesis methodology for these compounds. Indeed, in this reaction, all the atoms of the starting substrate are transferred to the product thus considerably reducing the waste produced. In addition, the amines and olefins employed are relatively inexpensive, abundant and varied reagents. Nevertheless, this simple transformation generally requires the use of a catalyst. In the literature, the hydroamination reaction of alkenes has been studied using alkali metal, alkaline earth, rare earth and transition metal complexes as catalysts. At the beginning of this project there were no examples of the hydroamination reaction of alkenes involving unprotected primary amines catalysed by iron or cobalt complexes. In this context, our team was interested in the reactivity of iron (II) and cobalt (II) complexes of low valence stabilized by β-diketiminate ligands. These complexes have proved to be excellent catalysts for promoting the hydroamination reaction of unprotected primary amines bound to non-activated alkenes.In a first step, the syntheses of the iron (II) and cobalt (II) complexes stabilized by β-diketiminate ligands as well as their applications in cyclohydroamination reaction of the unprotected primary amines will be presented. In addition, advanced mechanistic studies will clarify the mechanism of the reaction, which is proposed to go through a key elementary 1..2 migratory insertion leading to the formation of a carbon-nitrogen bond.In a second step, the influence of the electron and steric properties of the ligands on the reactivity in the hydroamination reaction of the alkenes of the iron (II) alkyl complexes will be studied. We will focus particularly on complexes stabilized by asymmetric β-diketiminate ligands or iminoanilides. The crystallographic data of the solid state complexes will then make it possible to rationalize the variations of reactivities of these various complexes.Finally, the iron (II) and cobalt (II) complexes synthesized above will be exploited to develop new reactivities in oxidation reactions, oxidative amination or the creation of a nitrogen-silicon bond by a dehydrogenating coupling
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23

Loiseau, Francis. "Cope-type Hydroamination of Alkenes with Hydroxylamines and Hydrazines - Scope and Mechanism." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/23794.

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Hydroamination stands as a desirable approach to nitrogen-containing molecules, which have important applications ranging from pharmaceuticals (fine chemicals) to paints, coatings, insecticides and agrochemicals (bulk chemicals). It features the use of alkene and alkyne starting materials, which are abundant and rarely used in the formation of C-N bonds. This work aims at building on the improved Cope-type reactivity developed in the Beauchemin group by expanding the reach of the reaction and understanding its mechanistic complexities. The first part of this thesis describes the development of cascade reactions to provide a thermodynamic driving force for the intermolecular Cope-type hydroamination of alkenes. The methodology serves as a proof of concept that the dipolar reaction intermediates can be engineered to further react irreversibly to more stable products, and has shown potential in improving the syntheses of natural alkaloids. The second part of the thesis describes the expansion of Cope-type hydrazide hydroaminations through a systematic investigation of hydrazine analogs as reactants. Optimized reagents are featured in the first reported intermolecular Cope-type hydrohydrazidation of alkenes. Mechanistic investigations and isolation of ammonium ylide intermediates support a 5-membered concerted and planar mechanistic pathway for hydrazide hydroaminations, similar to that observed with hydroxylamines. The final section presents mechanistic data disproving a previously assumed difficult proton transfer step in the hydroamination using hydroxylamines. From such findings, early results are presented towards a hydrogen-bond catalyzed hydroamination, which has potential applicability across the field of Cope-type hydroaminations and beyond.
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24

Thomson, Robert Kenneth. "Amidate complexes of the group 4 metals : sythesis, reactivity, and hydroamination catalysis." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/1344.

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A series of bidentate amidate ligands with variable groups R' and R" abbreviated by [R"(NO)R'] and adamantyl substituted tetradentate amidate ligands abbreviated by Ad[0₂N₂] were utilized as ancillaries for Ti, Zr, and Hf. Protonolysis routes into homoleptic amidate complexes, tris(amidate) mono(amido), bis(amidate) bis(amido), and bis(amidate) dibenzyl complexes are high yielding when performed with tetrakis(amido) and tetrabenzyl group 4 starting materials. Many of these complexes have been characterized in both the solid-state and in the solution phase, where in the latter case these complexes are fluxional and undergo exchange processes. Multiple geometric isomers are possible with the mixed N,0 chelate provided by the amidate ligands, and geometric isomerization of bis(amidate) bis(amido) complexes has been examined through X-ray crystallographic and density functional theory (DFT) calculations. Isomerization is dictated largely by the steric bulk present at the N of the amidate ligands, and is proposed to proceed through a K²-K¹-K² ligand isomerization mechanism, which is supported by crystallographic evidence of K¹-bound amidate ligands. The amidate ligand system binds to these metals in a largely electrostatic fashion, with poor orbital overlap, generating highly electrophilic metal centers. The bis(amidate) dibenzyl complexes of Zr and Hf are reactive towards insertion, abstraction, and protonolysis. Insertion of isocyanides into the Zr-C bonds of [DMP(NO) tBu]₂Zr(CH₂Ph₂ results in the formation of ƞ₂-iminoacyl complexes, which can either undergo thermally induced C=C coupling to generate an enediamido complex (aryl isocyanides), or rearrange to generate a bis(amidate) bis(vinylamido) complex (alkyl isocyanides). Benzyl abstraction to generate cationic Zr bis(amidate) benzyl complexes is also possible through reaction with [Ph₃C][B(C₆F₅)4] or B(C₆F₅)₃ Terminal imido complexes with novel pyramidal geometries are generated through protonolysis of bis(amidate) bis(amido) Ti and Zr complexes with primary aryl amines. DFT calculations demonstrate the existence of a Zr⁻₌N triple bond for these complexes. Dimeric imido complexes have been characterized in the solid state, but are not maintained in solution. Cycloaddition reactions of the terminal Zr imido complexes with C=0 bonds result in the formation of proposed oxo complexes and organic metathesis products. Catalytic aminoalkene cyclohydroamination has also been realized with these complexes, generating N-heterocyclic products. A series of kinetic and labeling studies support an imido-cycloaddition mechanism for catalytic cyclohydroamination of primary aminoalkenes with neutral bis(amidate) Ti and Zr precatalysts. The intermediate Ti imido complex, K²-[Dipp(NO)tBu-K¹_[DiPP(No) tBu]Ti=NCH₂CPh₂CH₂CH=CH₂(NHMe₂), has been isolated and characterized in the solid-state and in solution. Amine stabilized imido complexes of this type are invoked as the resting state for the catalytic reaction, and solution phase data support a chair-like geometry, where the alkene is coordinated to the metal center. A diastereoselectivity study supports this proposed solution structure. Eyring and Arrhenius parameters, as well as isolation of a 7-coordinate model imido complex, support a seven-coordinate transition state for the rate-determining metallacycle protonolysis reaction. In contrast, secondary aminoalkene hydroamination catalysis with cationic Zr benzyl complexes is proposed to proceed through a σ-bond insertion mechanism. Proton loss from cationic Zr amido complexes to generate imido species is proposed with primary aminoalkenes, and the resultant neutral imido complexes can catalyze the cyclization of these substrates by the aforementioned imido-cycloaddition mechanism. The ability of the amidate ligand system to promote both mechanisms is unique in the field of alkene hydroamination catalysis.
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25

Courtney, Sarah Turner. "Trifluoromethylated zirconium amidate complexes : new directions for the catalytic hydroamination of alkenes." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/9704.

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Hydroamination is the addition of an N–H bond across a C–C multiple bond. Nitrogen containing small molecules, typically accessed through multi-step synthetic pathways, are greatly important to both the pharmaceutical and fine chemical industries. Hydroamination is a rapidly expanding field due to the recent emphasis on sustainable chemistry for industrial applications as it provides an atom economical route to N-heterocycles, imines and amines. Group 4 catalysts have been greatly successful in this area however, intramolecular hydroamination of aminoalkenes typically proceeds only under high temperature reaction conditions. Low temperature reactivity is preferred from a practical perspective and is targeted here as a valuable probe to identify precatalysts most likely to display intermolecular alkene reactivity. The facile synthesis of organic amides provides a desirable means to adjust and optimize the steric and electronic properties of the proligand framework. Trifluoromethyl groups have been identified as desirable electron-withdrawing ligand substituents for the generation of reactive electrophilic zirconium hydroamination precatalysts. Proligand synthetic investigations revealed unforeseen challenges due to the electronic and steric effects imparted by trifluoromethyl substituents and unfortunately, the attractive 2,4,6-tris(trifluoromethyl) aryl-amides are of limited practical usefulness. In complex synthesis, the structure, bonding and reactivity screening of these novel electrophilic zirconium complexes will be presented as well as challenges associated with increased solubility. Importantly, these fluorinated systems have been shown to enhance reactivity of zirconium bis(amidate)bis(amido) complexes in the intramolecular hydroamination of alkenes. Progress toward low temperature (65 °C) reactivity will be discussed.
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26

Schulz, Robin [Verfasser]. "Process Development of the Homogenous Hydroamination Using Liquid-Liquid Systems / Robin Schulz." München : Verlag Dr. Hut, 2018. http://d-nb.info/1174425997/34.

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27

Bourgeois, Joffre. "Étude et développement de stratégies d'hydroaminations intramoléculaires et développement de la séquence tandem hydroamination de type Cope et réarrangement de Meisenheimer comme nouvelle stratégie pour les hydroaminations." Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28310.

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L'hydroamination d'alcènes est l'une des méthodologies les plus simples pour la formation de liens carbone-azote. Cependant, l'hydroamination d'alcènes est une transformation difficile peu développée dans la littérature scientifique. L'objectif vise des recherches présentées dans cette thèse était de développer des méthodologies efficaces pour les hydroaminations inter- et intramoléculaires.* Le chapitre 2 présente la tentative de synthèse de la dioscorine à l'aide d'une hydroamination intramoléculaire d'un haut niveau de difficulté pour former le squelette de l'isoquinuclidine, un bicycle tendu (équation 1). Suite à l'échec des différentes méthodologies testées et à la démonstration de la quasi thermoneutralité des hydroaminations d'alcènes intermoléculaires par le groupe de Hartwig, nous nous sommes penchés sur la conception d'une nouvelle stratégie d'hydroamination qui favoriserait thermodynamiquement la formation des produits d'hydroamination. Pour réaliser cette objectif ambitieux, nous avons entreprit le développement d'une séquence tandem, ou la deuxième réaction serait irréversible et produirait un produit plus stable. Avec une telle séquence tandem, les hydroaminations seraient sous contrôle cinétique, une condition essentielle pour le développement d'une méthodologie efficace et générale. Le chapitre 3 présente le développement de la séquence tandem hydroamination de type Cope/réarrangement de Meisenheimer (équation 2). Cette séquence tandem utilise la réactivité des hydroxylamines, préalablement développée par notre groupe de recherche, pour les hydroaminations de type Cope. La séquence tandem développée utilise la réactivité de l'intermédiaire N-oxide 2 pour induire une seconde réaction, soit le réarrangement de Meisenheimer. Il a été démontré que la séquence tandem était efficace pour l'hydroamination intermoléculaire d'alcènes tendus ou actives par un groupe fonctionnel. Des travaux effectués en parallèle ont également démontré la viabilité de la séquence tandem pour des hydroaminations intramoléculaires. *Please refer to dissertation for diagrams.
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28

Chapurina, Yulia. "Nouveaux complexes chiraux d'yttrium pour l'hydroamination intramoléculaire asymétrique des aminoalcènes." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA112219.

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Les hétérocycles azotés chiraux représentent une classe importante de composés biologiquement actifs. L’hydroamination asymétrique intramoléculaire correspond parfaitement au concept d’économie d’atomes et permet l’accès direct à la formation de nouvelles liaisons carbone-azote. Le développement de catalyseurs pour la formation de pyrrolidines et piperidines reste cependant une tâche importante. Le thème de cette thèse est l’étude de nouveaux complexes chiraux binaphthylamide d’yttrium facilement accessibles et leur application pour promouvoir la réaction d’hydroamination/cyclisation des amines primaires liées à des alcènes stériquement encombrés.Des complexes chiraux binaphthylamidure alkyl ate d’yttrium ont été développés. Ces systèmes catalytiques ont été préparés in situ par une réaction simple stœchiométrique en présence d’un précurseur d’yttrium [Li(THF)4][Y(CH2SiMe3)4] connu et d’une variété de ligands chiraux binaphthyldiamine substitués. Les complexes chiraux hétéroleptiques obtenus se sont révélés actifs et énantiosélectifs pour la réaction d’hydroamination asymétrique intramoléculaire des aminoalcènes 1,2-disubstitués conduisant à la formation d’hétérocycles azotés avec cinq et six châinons. Les catalyseurs d’yttrium préparés à partir du ligand (R)-N-anthrylmethyl-binaphthylamine H2L13 et des ligands (R)-benzyl N-para-substitués H2L4 or H2L6 se sont révélés les plus énantiosélectifs à 70-110°C pour la réaction d’hydroamination/cyclisation des aminoalcènes encombrés. Un excès énantiomérique de 77% a été obtenu comme valeur la plus élevée décrite jusqu’à présent pour l’hydroamination asymétrique intramoléculaire des amines comportant des alcènes 1,2-disubstitués. Les premiers exemples de la réaction d’hydroamination intramoléculaire asymétrique des aminoalcènes 1,1,2-trisubstitués ont été rapportés. Les complexes ate alkyl d’yttrium ont fourni les produits hétérocycliques avec des centres quaternaires énantiomériquement enrichis dans des conditions réactionelles plus sévères que la cyclisation des aminoalcènes 1,2-disubstitués et avec des énantiosélectivités prometteuses atteignant 55%. Les complexes alkyl d’yttrium contenant une molécule de chlorure de lithium [{(R)-C20H12(NSiMe3)2}Y{CH2SiMe3}{LiCl(THF)2}] and [{(R)-C20H12(NC5H9)2}Y{CH2SiMe3}{LiCl(THF)2}] ont été préparés et comparés aux mêmes complexes sans LiCl. Ils se sont révélés être des catalyseurs efficaces pour la réaction d’hydroamination intramoléculaire des aminoalcènes terminaux
Chiral nitrogen-containing heterocycles represent an important class of biologically active compounds. The asymmetric intramolecular hydroamination perfectly matches the concept of sustainable chemistry and allows the formation of new nitrogen-carbon bonds in an ideal atom efficiency and economy, starting from non activated substrates. The development of catalysts for formation of enantioenriched pyrrolidines and piperidines derivatives remains however a challenging task. The topic of this dissertation is the study of new easily accessible chiral yttrium binaphthylamide complexes and their application for promoting the hydroamination/cyclisation of primary amines tethered to sterically demanding alkenes. Chiral binaphthylamido alkyl ate yttrium complexes have been investigated. These catalytic systems have been prepared by a facile in situ stoichiometric reaction of a well-known yttrium precursor [Li(THF)4][Y(CH2SiMe3)4] with a variety of chiral substituted (R)-binaphthylamine ligands. These chiral heteroleptic complexes are shown to be efficient catalysts for the enantioselective intramolecular hydroamination of 1,2-disubstituted aminoalkenes leading to the formation of five and six-membered N-heterocycles. Yttrium catalysts prepared from (R)-N-anthrylmethyl-binaphthylamine ligand H2L13 and (R)-N-para-substituted benzyl ligands H2L4 or H2L6 proved to be the most enantioselective catalysts at 70-110°C for the hydroamination/cyclisation of challenging aminoalkenes. An enantiomeric excess value of 77 % was indeed disclosed as the highest value reported so far for the asymmetric intramolecular hydroamination of amines tethered to 1,2-disubstituted alkenes. The first examples of asymmetric intramolecular hydroamination of 1,1,2-tri-substituted aminoalkenes have been reported. The alkyl ate yttrium complexes produced the heterocyclic compounds with enantioenriched quaternary centres under harsher reaction conditions than the cyclisation of the corresponding 1,2-disubstituted alkenes, and with promising enantioselectivities of up to 55 %.The neutral alkyl yttrium complexes containing one molecule of lithium chloride [{(R)-C20H12(NSiMe3)2}Y{CH2SiMe3}{LiCl(THF)2}] and [{(R)-C20H12(NC5H9)2}Y{CH2SiMe3}{LiCl(THF)2}] have been prepared and compared with the same complexes lacking LiCl. They have been revealed as efficient catalysts for intramolecular hydroamination of terminal aminoalkenes
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29

Lau, Ying Yin. "Catalytic synthesis of N-heterocycles and alpha-alkylated amines by hydroamination and hydroaminoalkylation." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/60156.

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The research presented in this thesis emphasizes the versatility and utility of N,O-chelated early transition metals for the catalytic synthesis of -alkylated amines. Two major transformations were studied extensively in this work, hydroamination and hydroaminoalkylation. For both reactions, the synthetic utility and substrate scope has been expanded by the work presented herein. In the field of hydroamination, N-heterocycles with more than one heteroatom can now be synthesized using early transition metal catalysts from prochiral substrates. Hydroamination with a bis(amidate)bis(amido) complex of titanium of ether-containing aminoalkyne substrates yield cyclic imines, which are subsequently reduced via asymmetric transfer hydrogenation using the Noyori-Ikariya catalyst, RuCl [(S,S)-Ts-DPEN] (η⁶-p-cymene). 3-Substituted morpholines are synthesized using a one-pot sequential catalysis protocol, in good yields and high enantiomeric excesses. Substrate scope investigations reveal that high enantioselectivities in the asymmetric transfer hydrogenation reaction arise from key hydrogen bonding interactions between the oxygen heteroatom of the ether-containing cyclic imine and the [(S,S)-Ts-DPEN] ligand of Noyori-Ikariya catalyst. This mechanistic insight informed the proposal that this synthetic strategy can be extended to other substrates containing functional groups with hydrogen bond acceptors. As such, 3-substituted piperazines are also prepared with high enantioselectivities using this one-pot protocol. Advances to the hydroaminoalkylation transformation have also been made with the first reported example of room temperature reactivity observed using a phosphoramidate-tantalum complex. The preparation and characterization of a series of N,O-chelated phosphoramidate-tantalum complexes is described. These complexes were easily synthesized from either Ta(NMe₂)₅ by protonolysis or a simple organometallic precursor, TaMe₃Cl₂, by salt metathesis. Reactivity towards catalytic hydroaminoalkylation was explored and the results highlight that the choice of tantalum starting material dramatically affects the reaction temperatures required for catalytic turnover. N,O-chelated phosphoramidate dimethylamido tantalum complexes showed reactivity occurred only at elevated temperatures (≥ 90 °C), whereas phosphoramidate-tantalum complexes derived from TaMe₃Cl₂ exhibited unprecedented catalytic activity at room temperature. Preliminary efforts indicate that there is potential for an asymmetric version of hydroaminoalkylation at room temperature. Chiral phosphoramidate-tantalum complexes were prepared and studied as the first examples of asymmetric hydroaminoalkylation reactions at room temperature.
Science, Faculty of
Chemistry, Department of
Graduate
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30

Arrowsmith, Merle. "Intramolecular hydroamination of aminoalkenes with group 2 precatalysts : mechanistic insights and ligand design." Thesis, University of Bath, 2011. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538274.

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Long relegated to the background by the pre-eminence of magnesium-based, stoichiometric Grignard reagents, a distinct chemistry of the heavier alkaline earth metals, calcium, strontium and barium, is only now starting to emerge. As similarities have been drawn between the large, electropositive, redox-inert and d0 alkaline earth Ae2+ dications and the Ln3+ cations of the lanthanide series, a growing group 2-mediated catalytic chemistry has developed over the last decade, including polymerisation reactions, heterofunctionalisation reactions of multiple bonds and some rare examples of dehydrocoupling reactions. Among these catalytic reactions the magnesium- and calcium-catalysed intramolecular hydroamination of aminoalkenes has attracted particular interest. Mechanistic studies have demonstrated many parallels with the lanthanide-mediated catalytic cycle based upon successive σ-bond metathesis and insertion steps. In the first part of this thesis, further investigations into the hydroamination/cyclisation reaction have demonstrated the prominent role of the charge density of the catalytic group 2 cation (M = Mg, Ca, Sr, Ba), the beneficial influence of stabilising spectator ligands, and the importance of the choice of the reactive co-ligand for efficient catalyst initiation. Kinetic analyses of reactions monitored by NMR spectroscopy have given new insight into activation energies, entropic effects, substrate and product inhibition, and kinetic isotope effects, leading to a review of the previously suggested lanthanide-mimetic mechanism. In a second part, this study seeks to address two of the main challenges posed by the intramolecular hydroamination reaction in particular, and heavier alkaline earth-catalysed reactions in general: (i) The need to design new monoanionic spectator ligands capable of stabilising heteroleptic heavier alkaline earth complexes and preventing deleterious Schlenk-type ligand redistribution processes in solution; (ii) The stabilisation of highly reactive heteroleptic group 2 alkyl functionalities for fast, irreversible catalyst initiation and novel reactivity.
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31

Dion, Isabelle. "Intramolecular Cope-Type Hydroamination of Alkenes in the Synthesis of Alkaloids: Total Synthesis of (±)-Coniine and (±)-Desbromoarborescidine A and Studies on a Novel Amination Strategy Towards Manzamine A." Thesis, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23059.

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Intramolecular hydroamination represents a potentially general, simple strategy to access various nitrogen heterocycles. While important progress has been accomplished in recent years, six-membered ring formation via alkene hydroamination is typically difficult and limited to terminal alkenes, suggesting that only 2-methylpiperidines can be accessed reliably with current methods. As part of the Beauchemin group efforts on metal-free concerted hydroamination methods, the first part of this thesis describes the development of a Cope-type hydroamination-Meisenheimer rearrangement (CHMR) sequence that is applicable in inter- and intramolecular reactions. Data acquired from optimization on a difficult substrate (coniine) and the successful application of the CHMR sequence to the syntheses of N-norreticuline and 10-desbromoarborescidine are reported. The amination of alkenes is surprisingly scarcely used in the synthesis of complex alkaloids despite its potential for the construction of structurally challenging molecules while avoiding functional group interconversions. Hence, the second part of this thesis describes the studies on a novel amination sequence, consisting of an intermolecular Diels-Alder followed by an intramolecular hydroamination reaction, in the efforts towards the synthesis of biologically active and structurally complex Manzamine A. As such, the synthesis of the model substrates, including the development of a novel family of aminodienes, as well as the assessment of their reactivity towards [4+2] cycloadditions is reported.
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32

Aillaud, Isabelle. "Réaction d'hydroamination intramoléculaire énantiosélective catalysée par des complexes de terres rares." Paris 11, 2008. http://www.theses.fr/2008PA112123.

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Les hétérocycles azotés chiraux sont présents dans de nombreux composés naturels. L’hydroamination intramoléculaire énantiosélective permet l’accès direct à ces structures. La mise au point de catalyseurs permettant de réaliser cette transformation avec des énantiosélectivités élevées reste un véritable défi. Notre travail a consisté en l’étude de nouvelles familles de complexes N-substitué-(R)-binaphtylamidures de terres rares chiraux et leur utilisation en catalyse dans la réaction de cyclisation d’aminooléfines et aminodiènes non activés. Des complexes amidures ate de terres rares et de métaux alcalins ont tout d’abord été étudiés. Les complexes de lithium N-cyclopentyl-(R)-binaphtylamidures se sont révélés les plus énantiosélectifs et plusieurs pyrrolidines et une pipéridine ont été obtenues avec jusqu’à 87% ee. Les complexes comportant des groupements benzyles ou neopentyles, moins encombrés stériquement, ont été nettement plus actifs mais moins énantiosélectifs. De façon intéressante, les catalyseurs d’ytterbium correspondants ont permis de cycliser un aminopentène 1,2-disubstitué peu réactif, avec jusqu’à 38% ee. Des complexes amidures alkyles ate et neutres de terres rares ont également été préparés et testés. Ils sont nettement plus actifs que les précédents et ont conduit à plusieurs pyrrolidines et pipéridines diversement substituées dans des conditions douces avec jusqu’à 83% ee. Enfin, des aminodiènes non substitués ont été cyclisés avec des complexes amidures alkyles ate de terres rares. Le catalyseur de samarium N-cyclopentyl a conduit à la pyrrolidine correspondante avec jusqu’à 67% ee
Chiral nitrogen-containing molecules represent an important class of biologically active compounds. The catalytic asymmetric intramolecular hydroamination, an atom-economical process, is one of the most elegant procedures for the synthesis of these molecules. The development of catalysts to achieve this transformation with high enantioselectivities remains a challenging task. The topic of this thesis has been the study of new chiral rare-earth binaphthylamide complexes and their use for promoting various cyclisations of non-activated aminoalkenes and aminodienes. Binaphthylamido rare-earth ate complexes with alkaline counter ions have been first investigated. Lithium N-cyclopentyl catalysts (Ln = Yb, Y) proved to be the most enantioselective and several pyrrolidines and a piperidine were obtained with up to 87% ee. Catalysts with benzyl or neopentyl substituents are more active but less enantioselective. Interestingly, corresponding ytterbium complexes allowed the cyclisation of a more demanding 1,2-disubstituted amino-olefin, with up to 38% ee. New chiral rare-earth binaphthylamido alkyl ate complexes have been also prepared and studied as intramolecular hydroamination catalysts. They proved to be by far more active than the tetraamido rare-earth ate complexes and allowed the cyclisation of various aminoalkenes under mild conditions, with up to 83% ee. Moreover, aminodienes lacking gem substituents have been cyclised with rare-earth ate alkyl complexes. The N-cyclopentyl samarium derivative allowed the cyclisation of (E)-hepta-4,6-dien-1-amine with up to 67% ee
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33

Barber, David M. "The development of nitro-Mannich/hydroamination cascades for the synthesis of substituted N-heterocycles." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:18e7c533-3789-4800-9813-1d5c7bb4e4ea.

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This thesis describes the development of nitro-Mannich/hydroamination cascade reactions for the synthesis of N-heterocycles, which are important motifs found in a variety of biologically active natural products and pharmaceuticals, such as atorvastatin (Lipitor®). Chapter 2 outlines the development of an efficient synthesis of 2,5-disubstituted pyrroles using a nitro-Mannich/hydroamination cascade. Starting from easily prepared N-protected imines and nitroalkyne substrates, a compatible combination of KOtBu (10 mol%) and AuCl3 (5 mol%) was used to afford the desired pyrrole products, after an alkene isomerisation/HNO2 elimination reaction sequence. Chapter 3 describes the extension of this methodology to the diastereo- and enantioselective synthesis of 1,2,3,4-tetrahydropyridine derivatives using a nitroalkyne substrate with an extended carbon chain. The sequential addition of a bifunctional Brønsted base/H-bond donor organocatalyst and a gold complex was found to facilitate the desired cascade reaction affording substituted 1,2,3,4-tetrahydropyridine products. We then established that highly substituted pyrrolidine compounds could be prepared by replacing the nitroalkyne substrate with a nitroallene substrate (Chapter 4). The combination of KOtBu (5 mol%) and a gold catalyst derived from Au(PPh3)Cl (10 mol%) and AgSbF6 (20 mol%) was found to give an efficient diastereoselective synthesis of pyrrolidine derivatives after an additional nitro group epimerisation step. In addition, the nitro-Mannich/hydroamination cascade using nitroallene substrates was developed into an enantioselective variant using the previously employed bifunctional Brønsted base/H-bond donor organocatalyst. This afforded enantioenriched pyrrolidine derivatives.
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34

Brinkmann, Christine. "Heavier group 2 metals : application to intermolecular hydroamination, C-F activation and intramolecular hydroalkoxylation." Thesis, Imperial College London, 2011. http://hdl.handle.net/10044/1/9155.

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This thesis describes the reactivity of different heavier alkaline earth catalysts [M{X(SiMe3)2}2(THF)n]m (M = Ca, Sr, Ba; X = N, CH; n= 0, 2; m= 1, 2) in the intermolecular hydroamination of styrene derivatives. The scope of these reactions with respect to the substrate was determined and detailed kinetic studies to establish rate law and temperature dependence of the hydroamination reactions reported were conducted. Overall, it was found that [Ca{N(SiMe3)2}2]2 is favoured enthalpically (Ca: ΔH‡ = 51 kJ∙mol-1, Sr: ΔH‡ = 71 kJ∙mol-1) however the corresponding strontium bis(amide) proved a significantly better catalyst, likely due to a favourably high entropy of activation value (Ca: ΔS‡ = -168 J/mol-1 ·K-1, Sr: ΔS‡ = -92 J∙mol-1∙K-1). Large kinetic isotope effects of 4.1 and 7.9 at 55 °C for the intermolecular hydroamination of styrene with piperidine mediated by [Ca{N(SiMe3)2}2]2 and [Sr{N(SiMe3)2}2]2, respectively, suggest a rate-determining alkene insertion into the M-N bond with immediate or concerted protonolysis. The methodology used in these hydroamination reactions was extended to simple dienes, diphenylacetylene and an activated enyne. The catalyst initiation of the metal bis(amides) with piperidine was shown to be reversible and the equilibrium constant solvent dependent. Novel calcium and strontium dialkyl complexes [M{CH(SiMe3)2}2(THF)2] (M= Ca, Sr) were used to overcome the problem of catalyst initiation and showed a different solvent dependence. An enhanced reactivity was found for the dialkyl complexes compared to the metal bis(amides). This increased reactivity allowed the application in new reactions such as the C-F activation of fluorobenzenes. Furthermore, the use of these catalytic systems was successfully extended to intramolecular hydroalkoxylation reactions of alkynyl alcohols in the formation of five- and six-membered enol ethers. In this case, [Ba{N(SiMe3)2}2]2 displayed significant reactivity although the “catalyst of choice” for these reactions proved to be strongly dependent on substrate substitution pattern. Through detailed kinetic studies the catalyst, substrate and temperature dependence of the cyclisation reaction were established and an unusual rate law with inverse substrate dependence proposed.
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35

Ichikawa, Saki. "Copper-catalyzed carbon-heteroatom bond formations : asymmetric hydroamination and continuous-flow aromatic Finkelstein reaction." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/122852.

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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2019
Cataloged from PDF version of thesis.
Includes bibliographical references.
The studies presented in this dissertation are regarding the development of new methods for copper-catalyzed carbon-heteroatom bond formations, including asymmetric hydroamination and continuous-flow aromatic Finkelstein reaction. The first part of this dissertation focuses on the development of copper-catalyzed asymmetric hydroamination reactions to access various classes of enantioenriched amines. This includes the development of a broadly applicable hydroamination protocol for the synthesis of enantioenriched N-arylamines (Chapter 1) and 1,2- diamines (Chapter 2). The second part of this dissertation describes the development of copper-catalyzed aromatic Finkelstein reaction under continuous-flow conditions (Chapter 3). Part I. Chapter 1.
A Modified System for the Synthesis of Enantioenriched N-Arylamines through Copper-Catalyzed Hydroamination Despite significant recent progress in copper-catalyzed enantioselective hydroamination chemistry, the synthesis of chiral N-arylamines, which are frequently found in natural products and pharmaceuticals, has not been realized. Initial experiments with N-arylhydroxylamine ester electrophiles were unsuccessful and instead, their reduction, in the presence of copper hydride (CuH) catalysts, was observed. We detail key modifications of our previously reported hydroamination protocols that led to broadly applicable conditions for the enantioselective net addition of secondary anilines across the double bond of styrenes, 1,1 -disubstituted alkenes, and terminal alkenes. NMR studies suggest that suppression of the undesired reduction pathway is the basis for the dramatic improvements in yield under this new protocol. Chapter 2.
Regio- and Enantioselective Synthesis of 1,2-Diamine Derivatives by Copper- Catalyzed Hydroamination A highly regio- and enantioselective synthesis of 1,2-diamines using [gamma]-substituted allylic pivalamides via copper-catalyzed hydroamination is reported. The N-pivaloyl group is essential, both in facilitating the hydrocupration step and in suppressing the unproductive [beta]-elimination from the alkylcopper intermediate. This synthetic approach enables an efficient construction of chiral, differentially protected, vicinal diamines under mild conditions with broad functional group tolerance. Part II. Chapter 3. Rapid and Efficient Copper-Catalyzed Finkelstein Reaction of (Hetero)Aromatics under Continuous-Flow Conditions A general, rapid, and efficient method for the copper-catalyzed Finkelstein reaction of (hetero)aromatics has been developed using continuous flow to generate a variety of aryl iodides.
The described method can tolerate a broad range of functional groups, including N-H and O-H groups. Additionally, in lieu of isolation, the aryl iodide products in solution can be directly used in two distinct multistep continuous-flow processes (amidation or Mg-I exchange/nucleophilic addition) to demonstrate the flexibility of this method.
by Saki Ichikawa.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Chemistry
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36

Dub, Pavel A. "Hydroamination de l'éthylène : études expérimentales et théoriques de la catalyse au platine et de son mécanisme." Toulouse 3, 2010. http://thesesups.ups-tlse.fr/999/.

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L'hydroamination, l'addition de la liaison N-H sur une liaison CC insaturé en présence d'un catalyseur, est un sujet d'intérêt pour la recherche fondamentale et pour l'industrie chimique. Récemment l'hydroamination des oléfines non-activées utilisant des sels de PtII en présence de nBu4PX (l'activité la plus élevée étant donnée par le couple PtBr2/nBu4PBr) a été décrite [Brunet, J. J. Et all Organometallics 2004, 23, 1264-1268, Eur. J. Inorg. Chem. 2007, 4711-4722]. Il s'agit du système le plus efficace jamais décrit pour l'hydroamination de l'ethylène par des amines faiblement basiques comme l'aniline. Le but de cette thèse est 1) d'étudier le mécanisme (par des études expérimentales et par des calculs théoriques) de cette catalyse ainsi que 2) de transposer le système catalytique de Brunet vers des conditions biphasiques aqueses 3) de modifier le système catalytique de Brunet pour basculer la sélectivité vers la formation de quinaldine 4) comprendre les raisons pourquoi le système n'est pas actif pour des amines plus basiques
Hydroamination, addition of the N-H bond across unsaturated CC function in the presence of a catalyst, is a subject of interest for both industry and fundamental research. Recently, hydroamination of non-activated olefins using PtII salts in the presence of nBu4PX (the highest activity being given by the couple PtBr2/nBu4PBr) has been described [Brunet, JJ et all Organometallics 2004, 23, 1264 - 1268, Eur. J. Inorg. Chem. 2007, 4711-4722]. This is the most efficient system ever described for the hydroamination of ethylene with weakly basic amines such as aniline. The aim of this thesis is to 1) investigate the mechanism (by both experimental studies and theoretical calculations) of this catalysis and 2) to transpose the catalytic system of Brunet to biphasic aqueous conditions 3) modify the catalytic system of Brunet to switch the selectivity to the formation of quinaldine 4) to understand the reasons why the system is not active for more basic amines
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37

Bilodeau, Didier Alexandre. "Exploiting Intramolecularity: Exploring Aldehyde-Catalyzed Intermolecular Hydroaminations and Mixed Aminal Chemistry." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37100.

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Hydroamination reactions are very attractive to form new C-N bonds, though broadly applicable synthetic methods do not exist. The hydroamination of unactivated alkenes is especially difficult to accomplish given its negative reaction entropy, as well as potentially being a thermodynamically unfavourable transformation with some substrates. Thus, previously reported systems have often consisted of biased intramolecular systems or metal-catalyzed intermolecular variations operating at low temperatures. Recently, our group discovered that intermolecular Cope-type hydroamination of unactivated alkenes is achievable through the use of aldehydes as catalysts. These organocatalysts act solely through promoting the pre-association of reacting partners, hydroxylamines and allyl amines, in order to induce temporary intramolecularity; thus allowing for very mild reaction conditions and access to important 1,2-Diamine motifs. This thesis presents studies expanding upon initial reports of aldehyde-catalyzed Cope-type intermolecular hydroamination. In the scope of these studies standard conditions were developed to compare aldehyde catalytic activity. These evaluations led to further strengthening our understanding of hypothesized trends in aldehydes’ catalytic efficiencies, notably the impact of electronic, steric and solvent effects. Furthermore, the possibility of using a catalytic precursor species for hydroamination was evaluated. While this symmetrical hydroxylamine dimer precursor did not result in increased hydroamination yields, it did allow for easier manipulations as well as allow preliminary kinetic isotope effect studies to study formaldehyde as a precatalyst. These KIE studies allowed to reconfirm that hydroamination was highly likely the rate determining step of our proposed catalytic cycle. Derivatization of hydroamination products was also accomplished to access important 1,2 Diamine motifs from simple starting materials, also allowing to access difficult hydroamination products through the application of quantitative amounts of aldehyde, followed by hydrolysis of the formed heterocycles. Additional studies into nitrone reactivity led us to access a novel synthesis of enantiomerically enriched chiral cyclic nitrones through a sequence of nucleophilic addition, Cope-type hydroamination and Cope elimination. However, this sequence proved unpractical and of very narrow applicability, while affording only modest enantioselectivities (up to 78% ee), therefore further exploration was not warranted. A collaborative study was also undertaken in collaboration with the Wennemers group from ETH Zurich. This exploratory study had the goal of examining the potential for combining small peptide catalysis with aldehyde catalysis inducing temporary intramolecularity. It was hypothesized that the combination of both catalytic systems could improve upon the conjugate addition of nucleophiles to certain electrophiles, such as nitroolefins; in a potentially stereoselective manner. Although initial trials did not yield productive reactions, evidence for potential new mixed aminals with formaldehyde and various nucleophiles was found. Furthermore, the background reactivity of various nucleophile and electrophile pairings was assessed, allowing for better calibration of future efforts in studying such systems.
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38

Brown, Adam Ross. "I. Engaging Cationic Intermediates in Asymmetric Catalysis: Enantioselective Reactions of Carbenium Ions and N,N-Dialkyliminium Ions II. Enantioselective Catalysis of the Cope-Type Hydroamination by H-Bond Donors." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11009.

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The research described here explores the ability of dual H-bond donor catalysts to induce asymmetry in a variety of synthetically useful transformations that proceed via diverse reactive intermediates. In Chapters 1-3, we investigate ureas and thioureas as anion-binding catalysts for asymmetric reactions that proceeed via cationic intermediates with little precedent as electrophiles in asymmetric catalysis. Chapter 4 details our application of H-bond donor catalysis to the Cope-type hydroamination. Chapter 1 describes the development of an asymmetric aldehyde alkylation catalyzed by a bifunctional primary aminothiourea. A variety of 2-aryl propionaldehydes are alkylated with benzhydryl bromides in moderate to good yields and good enantioselectivities. Catalyst structure-activity relationship studies of the alkylation pointed towards electrophile activation by the dual H-bond donor moiety. Experiments aimed at gaining a better understanding of the electophile activation mode and characterizing the activated electrophilic intermediate in the alkylation reaction are described in Chapter 2. The development of an enantioselective cyanide addition to N,N-dialkyliminium intermediates is the subject of Chapter 3. A variety of strategies for accessing N,N- dialkyliminium ions are established, and chiral thioureas are shown to promote the addition of cyanide to such intermediates with moderate enantioselectivities. Chapter 4 details our discovery that thioureas bearing polarizable and conformationally constrained aromatic groups catalyze highly enantioselective Cope-type hydroaminations. This powerful transformation provides a variety of chiral pyrrolidine products under mild reaction conditions.
Chemistry and Chemical Biology
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39

Gribkov, Denis. "Novel catalysts for stereoselective hydroamination of olefins based on rare earth and group IV metals." [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=976595567.

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40

Purkait, Nibadita Verfasser], and Siegfried [Akademischer Betreuer] [Blechert. "Heterobimetallic and monometallic catalysts for asymmetric hydroamination and tandem reaction / Nibadita Purkait. Betreuer: Siegfried Blechert." Berlin : Universitätsbibliothek der Technischen Universität Berlin, 2012. http://d-nb.info/1026483808/34.

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41

Bennett, Stacey Danielle. "Novel Group 3/Lanthanide complexes and their application to intramolecular hydroamination and ring-opening polymerisation." Thesis, Cardiff University, 2013. http://orca.cf.ac.uk/58616/.

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This thesis describes the synthesis, characterisation and reactivity studies of a range of Group 3/Lanthanide complexes supported by bis(oxazolinyl)phenyl amide (BOPA). Chapter 1: Provides an introduction to the properties of the Lanthanides. Their application in asymmetric catalysis is reviewed, including catalysts supported by oxazoline ligands. Chapter 2 Describes density functional theory on a series of Group 3 BOPA complexes, the synthesis and characterisation of a new scandium amide-chloride precursor, thirty Group 3/lanthanide compounds supported by BOPA, six cation compounds supported by BOPA and three lithium BOPA compounds along with a discussion of the reactivity of compounds. Chapter 3: Describes the application of compounds described in Chapter 2 to the intermolecular hydroamination reaction of aminoolefins. Chapter 4: Describes a brief introduction to ring-opening polymerisation of rac-lactide and the application of compounds described in Chapter 2 to the ring-opening polymerisation of rac-lactide. Chapter 5: A brief introduction to luminescence is provided and the photophysical properties of a selection of diamagnetic complexes and all paramagnetic complexes discussed in Chapters 2 are described. Also, the synthesis, characterisation and photophysical properties of five Group 3/lanthanide compounds supported by pseudosubstrate ligands are described. Chapter 6: Details full experimental procedures and contains characterising data for all new compounds. Appendices A-B: Full tables of crystallographic data for all new crystallographically characterised compounds described herein are provided in Appendix A. Publications from this thesis are provided in Appendix B.
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42

Moran, Erik John. "Novel Synthetic Routes to Complex Amines: the Catalytic Hydroamination of Alkynes and Hydroimination of Allenes." Thesis, North Dakota State University, 2016. https://hdl.handle.net/10365/28036.

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Amines are valuable targets for synthesis in contexts of both research and industrial applications. This work proposes two atom-economical methods—hydroamination (HAM) and hydroimination (HIM)—as C-N bond formation strategies. A nickel-(N-heterocyclic carbene) catalyst system was developed to carry out HAM of internal, unactivated alkynes with aryl amines and cyclic secondary amines. It was demonstrated that the Ni-NHC catalyst was capable of promoting both HAM at room temperature and transfer hydrogenation to produce α-branched aryl amines. These two procedures were performed by the same catalyst to demonstrate an elegant 1-pot, multi-transformation protocol. Separately, optimization of a Rh-HIM catalyst system for the combination of monosubstituted allenes and aromatic N-H-ketimine was carried out to favor high conversion of substrates to the linear HIM product rather than [3+2] annulation. Both HAM and HIM C-N bond formation methods were found to be successful and capable of good conversion and selectivity for their respective products.
NSF (CHE-1301409 to R.M.) and ND-EPSCoR (RII-1330840)
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43

Rousseau, Géraldine. "Synthèse et désymétrisation d'arylcyclohexa-2,5-diènes : application à la synthèse totale de l'épi-Elwesine." Thesis, Bordeaux 1, 2008. http://www.theses.fr/2008BOR13654/document.

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La désymétrisation d’arylcyclohexa-2,5-diènes est une méthode très efficace pour obtenir en une seule étape des squelettes complexes à partir de synthons simples. Lors de cette thèse, une nouvelle approche à la synthèse d’arylcyclohexadiènes porteur d’un centre quaternaire a été développée. L’une des structures synthétisées par cette voie a ensuite été désymétrisée par une réaction d’hydroamination diastéréosélective, nous permettant de réaliser la première synthèse énantiosélective de l’épi-Elwesine. Notre démarche s’est ensuite orientée vers la synthèse et la désymétrisation de nouveaux types de diènes spirocycliques de type oxindoles. La présence dans ces diènes de deux faces très différenciées nous a permis de réaliser des processus complètement diastéréosélectifs. De plus une nouvelle séquence réarrangement-alkylation a été mise au point, nous permettant d’accéder efficacement à des squelettes de type phénanthridinones de façon régio- et diastéréosélective
The desymmetrization of arylcyclohexa-2,5-dienes is a powerful method to synthesize complex structures from simple synthons in a single step. We first developed a new protocol to obtain arylcyclohexa-2,5-dienes bearing a quaternary center. One of these structures was desymmetrized via a diastereoselective hydroamination and further elaborated into epi-Elwesine, an Amaryllidaceae alkaloid. We next turned our attention towards the synthesis and desymmetrization of spirocyclic cyclohexadienes. Diastereoselective processes were carried out due to the presence of two well- differentiated faces. A new rearrangement-alkylation process was developed and provides efficient access to phenanthridinones regio- and diastereoselectively
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44

Tafazolian, Hosein. "Hydroamination and Hydrosilylation Catalyzed by Cationic Palladium- and Nickel(allyl) Complexes Supported by 3-Iminophosphine Ligands." University of Toledo / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1473397460390363.

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45

Wood, Mark Christopher. "Synthesis of chiral bis(amidate)bis(amido) titanium and zirconium complexes for catalyzed asymmetric alkene hydroamination." Thesis, University of British Columbia, 2006. http://hdl.handle.net/2429/31695.

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Recent advances in transition metal and lanthanide catalyzed hydroamination have changed the way people think about the formation of C-N bonds. As a major contribution to this area of research, we have synthesized the first neutral group 4 precatalysts capable of enantioselective alkene hydroamination. We took advantage of a modular amidate ligand set to alter both the electronic and steric properties of the precatalysts. The amidate ligands employed in these catalysts were synthesized by reacting an axially chiral 2,2'diamino-6,6'-dimethylbiphenyl diamine with a corresponding acyl chloride or anhydride. Further reaction of the chiral amide proligand with Ti(NMe₂)₄ or Zr(NMe₂)₄, produced the bis(amidate)bis(amido) titanium and zirconium precatalysts in quantitative yields. [formula omitted] Enantioselectivity and reactivity investigations for aminoalkene hydroamination were conducted on the group 4 complexes prepared, and complex A produced the most excellent enantioselectivities. From this investigation, minor alterations to the electronic and steric properties of the ligand showed significant effects on reactivity and enantioselectivity. Further substrate scope investigations, using precatalyst A, displayed high yields, moderate reaction times and enantioselectivities up to 93% ee. Most importantly, the structural and substrate scope investigation provided a mechanistic rationale for observed trends in reactivity and enantioselectivity, yielding valuable insight for future catalyst development.
Science, Faculty of
Chemistry, Department of
Graduate
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46

Chu, Ngoc Chau. "Hydroamination intermoléculaire des liaisons multiples carbone–carbone dans les solvants ioniques : effet activant de n-Bu4PBr." Toulouse 3, 2005. http://www.theses.fr/2005TOU30223.

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Nous avons mis au point le premier système catalytique à base de platine (PtBr2/n-Bu4PBr/H+) efficace (activité et régioséléctivité) pour l'hydroamination des oléfines non activées (norbornène, éthylène, hex-1-ène). Plus de 200 cycles catalytiques ont été obtenus (éthylène, hex-1-ène), qui plus est avec une régioselectivité de 95 % en produit d'addition Markovnikov (hex-1-ène), et sans nécessité de manipuler sous atmosphère inerte. La voie est ouverte à l'hydromination énantiosélective des oléfines supérieures. Le rôle activant des ions bromures du sel de phosphonium a été démontré, et un cycle catalytique a été proposé, qui permet d'expliquer à quel niveau intervient cette activation. Il a également été montré pour la première fois que PtBr2 catalyse l'hydroamination régiosélective (Markovnikov) des acétylèniques terminaux en imines correspondantes
The platinum-catalyzed intermolecular hydroamination of alkenes (norbornene, ethylene, hex-1-ène) is reported for the first time. The ligandless, non-toxic PtBr2/n-Bu4PBr/H+ catalytic system allows reaching TON ≥ 200 (ethylene, hex-1-ène). Furthermore, a 95 % Markovnikov regioselectivity is observed (hex-1-ène), thus opening the way to enantioselective hydroamination in the presence of well-suited chiral ligands. The same results are obtained for reactions performed in the air. An activating role of n-Bu4PBr has been clearly evidenced, which is due to the presence of the bromide ions. An overall mechanism has been proposed which explains at which level this activation occurs. It has also be shown for the first time that PtBr2 catalyses the regioselective (Markovnikov) hydroamination of terminal alkynes to the corresponding imines
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47

Zingales, Nicholas C. "Investigation of the Steric and Electronic Properties of 3-Iminophosphine Ligands in Chelated Palladium Allyl Complexes for Use in the Regioselective Hydroamination of Allenes." University of Toledo / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1356544579.

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48

Bahri, Janet. "Nouvelles méthodes d'hydroamination d'alcynes." Thesis, Montpellier, Ecole nationale supérieure de chimie, 2015. http://www.theses.fr/2015ENCM0019/document.

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Au cours de cette thèse, nous avons développé la réaction d'hydroamination d'arylacétylènes en présence de quelques amines secondaires aliphatiques. Dans un premier temps, nous avons pu montrer que cette réaction peut être catalysée par différents sels de cuivres. L'utilisation catalytique de CuCN a permis la formation régio- et stéréosélective d'énamines issues d'addition d'orientation de type anti-Markovnikov d'isomèrie (E). Les conditions développées n'ont pas permis la purification des énamines observées. Pour cette raison une réduction en présence de l'agent réducteur NaBH3CN a été effectuée afin de pouvoir isoler les amines correspondantes. L'utilisation catalytique de CuCl a permis à son tour, dans certaines conditions, la synthèse régio-et stéréosélective de 1,3-diènes (1E,3E)-1,4-disubstitués. La nature des électroniques des substituants des noyaux aromatiques des alcynes employés a joué un rôle majeur en ce qui concerne la chimiosélectivité de la réaction. Dans un second temps, nous nous sommes concentrés sur l'amélioration des conditions développées et la recherche d'autres moyens plus efficaces, moins coûteux et plus verts, nous avons été en mesure de montrer que la réaction étudiée peut également s'effectuer uniquement en présence d'éthylène glycol employé en tant que solvant et promoteur de la réaction. Cette méthode permet l'accès direct aux énamines issues de l'addition d'orientation de type anti-Markovnikov d'isomérie (E) avec d'excellents rendements isolés sans qu'il soit nécessaire de purifier les énamines obtenues
In this thesis, we developed the hydroamiantion arylacétylènes reaction in the presence of some aliphatic secondary amines. At first, we could show that this reaction can be catalyzed by various copper salts. The catalytic use of CuCN allowed the regional training and sétéréosélective enamines derived from anti-Markovnikov addition type orientation isomerism (E). Developed conditions have not allowed the purification of the observed enamines. For this reason a reduction in the presence of the reducing agent NaBH3CN was performed in order to isolate the corresponding amines. The catalytic use of CuCl enabled in turn, under certain conditions, the regio-and stereoselective synthesis of 1,3-dienes (1E, 3E) -1,4-disubstituted oxanilides. The electronic nature of substituents of the aromatic rings alkynes employed played a major role as regards the chemoselectivity of the reaction.Secondly, we concentrate developed to improve conditions and find other more efficient ways, cheaper and greener, we were able to show that the test reaction can also be carried out only in the presence ethylene glycol used as solvent and the reaction promoter. This method allows direct access to enamines from the addition anti-Markovnikov orientation type of isomerism (E) with excellent isolated yields without the need to purify the resulting enamines
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49

Germain, Stephane. "Réaction d'hydroamination régiosélective catalysée par des sels de lithium ou par des complexes d'yttrium, de zirconium ou d'hafnium." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA112272/document.

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L’addition d’une liaison N-H sur une double liaison carbone-carbone, nommée réaction d’hydroamination (HA), constitue une voie efficace pour accéder à la formation de composés azotés à partir de précurseurs simples en une seule étape. Des progrès considérables ont été réalisés au cours de ces dernières années dans l’élaboration de systèmes catalytiques efficaces pour cette réaction d’intérêt sur des alcènes. Malgré tout de nombreux défis subsistent car peu de catalyseurs disposent d’un large champ d’application ou encore ils sont limités dans la catalyse de la version intermoléculaire de la réaction à la fois moins favorisée cinétiquement comme thermodynamiquement. Au cours de ces travaux le mécanisme réactionnel, d’activation de la réaction d’HA intramoléculaire, par un complexe d’yttrium a pu être déterminé suite à une étude cinétique. Cette dernière a permis de mesurer un ordre partiel en catalyseur de 1 et un ordre inverse en substrat. D’autre part, le potentiel dans la réaction d’HA de plusieurs systèmes catalytiques basés sur différents groupes de métaux a été évalué. Des complexes pinces tridentes de zirconium ou de hafnium sous forme neutre comme sous forme cationique ont montré de bonnes activités dans la réaction de cyclisation de plusieurs aminoalcènes comportant des amines primaires ou secondaires. L’utilisation d’un complexe d’yttrium a permis d’accéder à une large gamme d’arylethylamines de manière totalement régiospécifique par catalyse de la réaction intermoléculaire d’HA entre des amines secondaires faiblement encombrées et des dérivés du styrène. Ce faisant une étude structure-activité a été conduite mettant à jour une activité remarquable du complexe d’yttrium dans la réaction d’HA intermoléculaire sur la 2-vinylpyridine, ce qui a également permis de montrer une application en procédure tandem de double hydroamination. Enfin une procédure simple de catalyse de la réaction d’HA intermoléculaire sur des dérivés du styrène a pu être mise au point suite à l’utilisation d’un sel de lithium actif à température ambiante
The addition reaction of an amine across a carbon-carbon double bond, the so-called hydroamination reaction, is one of the most efficient method for the formation of value-added nitrogen-containing compounds. During the last decade, the interest of the scientific community has led to the development of a large number of efficient catalysts for this transformation. Nevertheless many challenges remain. Indeed only a few of the reported catalysts have a wide range of applications or possess good activities in the field of the intermolecular version of the reaction, less favored both kinetically and thermodynamically. In these work the mechanism of intramolecular HA reaction catalyzed by an yttrium complex has been determined by a kinetic study. During the latter a partial order of 1 for the catalyst and a reverse order in substrate were measured. The potential in the HA reaction of several catalytic systems based on different metals was evaluated. Tridentate complexes of zirconium or hafnium in their neutral or cationic form showed good activity in the cyclization reaction of several aminoalkenes bearing primary or secondary amines. The use of an yttrium complex allowed a regiospecific access to wide range of arylethylamines by catalysis of the intermolecular HA reaction between weakly hindered secondary amines and styrene derivatives. A structure-activity study was conducted pointing the noteworthy activity of the yttrium complex in the intermolecular HA reaction with 2-vinylpyridine, which also allowed an application in a tandem di-hydroamination reaction. Finally, a simple procedure for catalyzing the intermolecular HA reaction of styrene derivatives has been developed by using a lithium salt active at room temperature
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50

Soklou, Kossi Efouako. "Synthèse d'hétérospirocycles par hydroaminations et hydroalkoxylations d'alcynes catalysées par l'or (I) - Méthodologie et application au développement de fragments spirocycliques pour la chimie médicinale." Thesis, Orléans, 2020. http://www.theses.fr/2020ORLE3066.

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Synthétiser des molécules azotées ou oxygénées spiro [4.5] ou spiro [5.5] possédant une liaison entre le carbone spiranique et l’atome d’azote ou d’oxygène reste un défi même si ces fragments sont représentés dans la nature et dans l’arsenal thérapeutique. Pour lever cette contrainte, nous avons développé une méthode générale de spirocyclisation catalysée par l’or (I) passant par des réactions d’hydroamination ou d’hydroalkoxylation d’alcynes. Dans la première partie de cette thèse, nous avons pu optimiser les conditions de spirocyclisation à base de JohnPhosAu(CH3CN)SbF6 en série azotée et oxygénée avec les alcynes vrais, puis accéder à des spirocycles tricycliques originaux par des réactions en cascade. Nous avons également démontré la robustesse de notre méthode vis-à-vis des composés chiraux. Dans la deuxième partie de ce travail, la méthode de spirocyclisation a été étendue aux alcynes disubstitués grâce au couple JohnPhosAuCl/AgNTf2. Dans la troisième partie, nous avons effectué la transformation des spirocycles afin d’accroître la diversité moléculaire. Pour ce faire, des réactions de Mizoroki-Heck intramoléculaires ont fourni des spirocycles tétracycliques originaux et stables tandis que d’autres réactions comme des réductions ont, en plus de la stabilité, accru leur tridimensionnalité. Avec tous ces fragments, un programme de chimie médicinale a été engagé et des actifs à motifs spirocycliques ont été élaborés comme inhibiteurs sélectifs de kinases
The synthesis of spiro [4.5] or [5.5] nitrogen or oxygen containing molecules with a bond between the carbon spirocenter and the nitrogen or oxygen atom remains a challenge, even if these fragments are represented in nature as well as in the therapeutic arsenal. To overcome this constraint, we have developed a general method of gold (I) catalyzed spirocyclization through the hydroamination or hydroalkoxylation of alkynes. In the first part of this thesis, we optimized spirocycle formation in both the nitrogen and oxygen series using conditions based on JohnPhosAu(CH3CN)SbF6 with unsubstituted alkynes. This also gave access to original tricyclic spirocycles by cascade reactions. We then demonstrated the robustness of our method with respect to chiral compounds. In the second part of this work, the spirocyclization method was extended to di-substituted alkynes using the combined JohnPhosAuCl/AgNTf2 catalyst. In the third part, we transformed our different spirocycles to increase molecular diversity. Intramolecular Mizoroki-Heck reactions provided original and stable tetracyclic spirocycles while other reactions such as double bond reduction increased both stability and 3D molecular space. With these fragments in hand, a medicinal chemistry program was initiated and spirocyclic compounds were developed as selective kinase inhibitors
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