Dissertations / Theses on the topic 'Precatalyst'

This thesis describes the use of in situ infrared spectroscopy to investigate the kinetics and mechanism of Pd-catalysed arylcyanation. These studies probe the formation of small Pd nanoclusters in the Pd catalysed cyanation of aryl halides. Initially, an overview of the role of Pd nanoparticles and Pd nanoparticle precursor complexes in Pd-catalysed reactions is provided. The application of the established precatalyst in extensive kinetic studies of arylcyanation has revealed that there is clear evidence for heterogeneous catalytic behaviour (Chapter 4). A significant change in kinetic profile supports a change in precatalyst activation mechanism. Pd concentration and catalyst loading data, along with computational analysis, support a role for small Pd clusters in catalysis (Chapter 5).

Metathesis reactions are of great value for industrial processes e.g. Shell Higher Olefin Process (SHOP) to form new alkenes. A lot of catalytic systems were developed to optimize the activity, stability and selectivity of these precatalysts. In a previous study a Grubbs 2-type precatalyst (Gr2Ph (3)) which had a N^O hemilabile ligand with two phenyl groups coordinated to the Ru-metal was developed. This Grubbs 2-type precatalyst, known as the Puk-Grubbs 2-precatalyst (Gr2Ph (3)) was used for 1-octene metathesis reactions and showed an increase in the selectivity, thermal stability, activity and lifetime In comparison to Grubbs 1 (Gr1 (1)) and Grubbs 2 (Gr2 (2)). In order to determine if the precatalyst is of value to metathesis reactions it was used for different 1-alkenes (1-hexene, 1-heptene, 1-nonene and 1-decene) and the conditions optimized. The Gr2Ph (3) precatalyst was successfully synthesized (43% yield) in this study and used for the metathesis reactions of the different 1-alkenes. The metathesis reactions of each 1-alkene was conducted at different temperatures, 55°C and 60°C for 1-hexene reactions, 60°C, 70°C and 80°C for 1-heptene reactions and 60°C, 80°C and 100°C for 1-decene reactions, except 1-nonene, while the Ru:1-alkene ratios were varied for 1-hexene and 1-heptene (1:7000 and 1:9000). The results of the 1-alkene metathesis reactions showed that the Gr2Ph (3) precatalyst increased the lifetime to 35 days and thermal stability when compared to Gr1 (1) (1 hour lifetime) and Gr2 (2) (3 hours lifetime). The TON, selectivity and activity is comparable to those of the Gr2 (2) reaction results, whilst an improvement on the Gr1 (1) results was obtained. The optimum conditions in terms of TON, PMP formation and selectivity for Gr2Ph (3) was found to be at 80°C with a 1:7000 Ru:1-alkene ratio for 1-heptene and 1-decene, but the ethylene accumulation In the mini reactors had an impact on the results. The ethylene accumulation resulted in the conversion of the already formed PMPs into SMPs and IPs during the course of the reaction. The optimum temperature for the 1-hexene reactions were determined to be at 60°C for Gr2Ph (3) with a Ru:1alkene ratio of 1:7000, with a high PMP formation, selectivity and TON. The 1H-NMR investigation of the metathesis reactions of 1-octene and 1-hexene with Gr2Ph (3) in CDCI3 at 30°C with a Ru:1-alkene ratio of 1:40, showed that only one carbene signal was present. Metathesis products were formed and confirmed with GC-MS and a larger amount of SMPs and IPs were formed by the competing isomerization reactions. These results indicate that metathesis does occur but that another mechanism was present or that the ligand was not hemilabile as suspected.<br>Thesis (Ph.D. (Chemistry))--North-West University, Potchefstroom Campus, 2010.

Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2015.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references.<br>[Chemical formula] A series of air-stable nickel complexes of the form L₂Ni(aryl)X (L = monodentate phosphine, X = Cl, Br) and LNi(aryl)X (L = bis-phosphine) have been synthesized and are presented as a library of precatalysts suitable for a wide variety of nickel-catalyzed transformations. These complexes are easily synthesized from low-cost NiCl₂-6H₂O or NiBr₂-3H₂O and the desired ligand followed by addition of 1 equiv of Grignard reagent. A selection of these complexes were characterized by single-crystal X-ray diffraction, and an analysis of their structural features is provided. [Chemical formula] The air-stable nickel(II) complex trans-(PCy₂Ph)₂Ni(o-tolyl)Cl was employed as a precatalyst for the Mizoroki-Heck-type, room temperature, internally selective coupling of substituted benzyl chlorides with terminal alkenes. This reaction, which employs a terminal alkene as an alkenylmetal equivalent, provides rapid, convergent access to substituted allylbenzene derivatives in high yield and with regioselectivity greater than 95:5 in nearly all cases. The reaction is operationally simple, can be carried out on the benchtop with no purification or degassing of solvents or reagents, and requires no exclusion of air or water during setup. Synthesis of the precatalyst is accomplished through a straightforward procedure that employs inexpensive, commercially available reagents, requires no purification steps, and proceeds in high yield. [Chemical formula] The nickel-catalyzed cross-coupling of aliphatic N-tosylaziridines with aliphatic organozinc reagents is described. The reaction protocol displays complete regioselectivity for reaction at the less hindered C-N bond, and the products are furnished in good to excellent yield for a broad selection of substrates. An air-stable nickel(II) chloride/ligand precatalyst was also developed and employed for the reaction. In addition to increasing the activity of this catalyst system, this also greatly improves the practicality of this reaction, as the use of the very air-sensitive Ni(cod)₂ is avoided. Finally, mechanistic investigations, including deuterium-labeling studies, show that the reaction proceeds with overall inversion of configuration at the terminal position of the aziridine by way of aziridine ring opening by Ni (inversion), transmetallation (retention), and reductive elimination (retention).<br>by Eric A. Standley.<br>Ph. D. in Organic Chemistry

2016 - 2017<br>Olefin metathesis is one of the most important chemical transformations for the formation of carbon-carbon double bonds. The possibility to build up highly funtionalised alkenes starting from simple olefins makes this reaction indispensable in modern organic synthesis, giving access to a wide range of molecules that would be barely obtained through other synthetic routes. The success of metathesis is due to the development of new and efficient catalysts which can be used in a wide variety of research fields, both in industry and in academia. In this context, the research of the ‘perfect’ metathesis complex still impassions scientists all over the word, and several research papers regarding the development of new catalytic systems are published every year. The group I am part of focuses its attention on the development of new ruthenium metathesis catalysts. Our interest lies in the influence that nature and configuration of substituents on the N-heterocyclic carbene (NHC) ligand could have on the performances of the corresponding metal complexes. In this doctoral thesis, the field of unsymmetrical N-heterocyclic carbene (u-NHC) ruthenium catalysts will be explored. Synthesis and characterisation of several novel complexes will be discussed. Catalytic performances will be evaluated in model metathesis reactions as well as in more attractive metathesis transformations. The relationship between NHC structure and complexes’ behaviours will be investigated using NMR, X-Ray, IR, cyclic voltammetry and DFT calculations. ..[edited by Author]<br>XXX ciclo

Metathesis is a valuable reaction for the production of new alkenes. In the last 50 years, heterogeneous as well as homogeneous catalysts have been used for this reaction. In the homogeneous category are the very successful catalysts designed by the Grubbs group. The first generation Grubbs precatalyst (Gr1) bearing two phosphine ligands was followed after extensive studies by the more active second generation Grubbs precatalyst (Gr2). In Gr2, one of the phosphine ligands is replaced with an N-heterocyclic carbene. Grubbs type precatalysts bearing pyridynyl-alcoholato chelating ligands are pertinent to this study. Scheme 1: The synthesis of Grubbs type precatalysts bearing a pyridynyl-alcoholato ligand. In two previous studies, both supported by computational methods, Grubbs type precatalysts with N^O chelating ligands were synthesised. These investigations were motivated by the fact that chelating ligands bearing different donor atoms can display hemilability. The loosely bound donor atom can de-coordinate to make available a coordination site to an incoming substrate “on demand”, whilst occupying the site otherwise and hence preventing decomposition via open coordination sites. In the first investigation, the incorporation of an O,N-ligand with both R1 and R2 being phenyl groups into the Gr2 precatalyst, resulted in an increase in activity, selectivity and lifetime of the precatalyst in comparison to Gr2 in the metathesis reaction with 1- octene. In the second study, three synthesised complexes were found to be active for the metathesis of 1-octene. This computational study sought to better understand the structural differences and thermodynamic properties of these Grubbs type precatalysts with bidentate/hemilabile ligands. A large number of structures were constructed in Materials Studio by varying the R groups of the bidentate/hemilabile ligand attached to both the Gr1 and Gr2 catalysts. The majority of structures were Gr1-type complexes. For each ligand selected, a group of structures consisting of closed precatalyst, open precatalyst, and where applicable a precatalyst less PCy3, closed metallacycle, open metallacycle and where applicable a metallacycle less PCy3, was constructed and optimised using DMol3. Bond lengths, bond angles, HOMO and LUMO energies and Hirshveld charges of structures were compared with one another. PES scans were performed on the metallacycles of four groups. The purpose of the PES scans was to ascertain whether these bidentate ligands were hemilabile and to illuminate the preferred reaction mechanism for these types of precatalysts. The major finding of this study was that the possibility of an associative mechanism cannot be ruled out for some Gr2-type precatalysts with bidentate ligand. For some precatalysts hemilability is energetically expensive and possibly not viable. No evidence of a concerted mechanism was found. The dissociative mechanism was found to be the preferred mechanism for most of the structures that were subjected to PES scans. The HOMO-LUMO energies of a complex can be used, as a predictive tool, to assess the reactivity and stability of a complex, as well as its preference for substrates.<br>Thesis (MSc (Chemistry))--North-West University, Potchefstroom Campus, 2013.

A series of new aryl ether salicylaldimine-based monomeric, dimeric, trimeric and hexameric triazolyl ligands have been synthesised. The N,O-chelating ligands were synthesised via Schiff base condensation reactions of salicylaldehyde with the bromopropylamine hydrobromide salt, followed by the azidation of the resultant N-3-bromopropylsalicylaldimine. Click chemistry reactions of the azido propyl salicylaldimine with the appropriate phenolic-alkyne afforded the mono-, di-, tri- and hexameric aryl ether salicylaldimine-based triazolyl ligands. The ligands were characterised using various analytical and spectroscopic techniques. Complexation of the monomeric and trimeric ligands with the dimeric rhodium precursor [RhCl(COD)]2 yielded new aryl ether N,O-chelate mononuclear and trinuclear Rh(I) complexes. The complexes were characterised using nuclear magnetic resonance spectroscopy, infrared spectroscopy, mass spectrometry and melting point determinations. The mononuclear and trinuclear complexes were successfully evaluated as catalyst precursors in the hydroformylation of higher olefins. The reaction conditions were optimised using the mononuclear precatalyst at 85 ℃, 40 bar syngas pressure for 4 h with 2.87 x 10-3 mmol Rh loading and a substrate (1-octene) to catalyst ratio of 2500 : 1. These conditions gave good aldehyde chemoselectivity (90%), excellent conversion of the substrate (99%) and good catalytic activity (554 h-1 ). Comparable catalytic performance of both precatalysts was obtained when milder reaction conditions (85 ℃, 20 bar for 4 h) were adopted in the evaluation of the mononuclear complex against the low generation dendritic trinuclear complex. The mercury poisoning experiments revealed a dual catalytically influenced system, emanating from a combination of homogeneous and heterogeneous catalytic species. The mononuclear catalyst precursor was also evaluated successfully in the hydroformylation of internal olefins 7- tetradecene and trans-4-octene. The catalyst precursor gave good conversions of both internal olefins (> 80%) under the optimum reaction conditions (85 ℃, 40 bar for 4 h). Catalyst recyclability studies in the hydroformylation of 1-octene conducted using the Organic Solvent Nanofiltration (OSN) strategy demonstrated five successful recycles with consistently good catalytic performance from both catalyst precursors. Inductively coupled plasma optical emission spectrometry (ICP-OES) experiments revealed a near perfect (99%) membrane retention of the rhodium metal. Kinetic studies using the mononuclear precatalyst were investigated by evaluating the effect of temperature, syngas total pressure and catalyst loading on the rate of hydroformylation. The activation energy for the hydroformylation of 1-octene was calculated to be 62 kJ mol-1 and the experimental rate constants were found to be in good agreement with the predicted rate data obtained using a modified fundamental mechanismbased rate model. The synthesis and characterisation of new water-soluble, sulfonated aryl ether salicylaldiminebased mono- and trimeric ligands has also been described. The ligands were prepared following a series of amine and Boc-protection and deprotection procedures, Schiff base condensation reactions and Williamson ether synthesis. The water-soluble N,O-chelating aryl ether ligands were characterised using various spectroscopic and analytical techniques. Subsequently, complexation reactions of the ligands with the dimeric [RhCl(COD)]2 gave the corresponding new water-soluble mononuclear and trinuclear Rh(I) complexes. The complexes were characterised using nuclear magnetic resonance spectroscopy, infrared spectroscopy, mass spectrometry and melting point determinations. The complexes show appreciably good solubility in water, 15.7 mg/mL (mononuclear complex) and 8.6 mg/mL (trinuclear complex). The new water-soluble mono- and trinuclear complexes were successfully evaluated as precursors in the aqueous biphasic hydroformylation of higher olefins. Optimisation experiments using the mononuclear precatalyst gave the best results at 85 ℃, 50 bar syngas pressure for 4 h with 2.87 x 10-3 mmol Rh loading and a substrate (1-octene) to catalyst ratio of 2500 : 1. Both catalyst precursors gave near quantitative catalytic conversion of 1-octene, good activities (> 550 h -1 ) and attractive aldehyde chemoselectivity (> 85%). A substrate and product-distribution time study showed a positive dendritic effect in relation to the trinuclear complex over the mononuclear complex. The mercury poisoning experiments were suggestive of a system that is catalysed by a dual effect of homogeneous and heterogeneous catalytic species. Recyclability experiments were successfully conducted over 5 cycles, with a gradual decline in catalytic performance for both complexes. The dendrimer stabilised trinuclear precatalyst showed improved recyclability in “neat”, monophasic hydroformylation experiments, while the mononuclear precatalyst showed a reduced overall performance. The bias towards the linear aldehyde for the dendritic trinuclear complex was tunable by addition of excess bulkier trimeric water-soluble ligand into the catalytic system. Inductively coupled plasma optical emission spectrometry experiments showed moderate losses of the metal from the aqueous phase to the organic layer. Both catalyst precursors also showed good catalytic activity (> 450 h-1 ) and a total bias to aldehyde chemoselectivity (no hydrogenation products) in the aqueous biphasic hydroformylation of styrene.

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.

This work deals with two independent research topics with the common goal of finding ways to render catalytic processes more efficient and sustainable by lowering their environmental impact. The first part of this thesis deals with the design of ruthenium-based olefin metathesis pre-catalysts for organic solvent nanofiltration (OSN). OSN is an environmentally friendly separation process attracting academic and industrial interests for the removal of organometallic residues as well as for catalysts recycling. For this work, new pre-catalysts based on the Hoveyda-Grubbs architecture containing modifications on the isopropoxystyrene as well as on the N-heterocyclic carbene (NHC) ligands were prepared and fully characterized. The catalysts were evaluated for their catalytic activities under standard conditions and were then subjected to Nanofiltration (NF) studies. In the second part of this work, the catalytic, acceptorless dehydrogenation of alcohols was explored. In the first instance, [RuCl₂(p-cymene) IMes] was evaluated in the dehydrogenation of alcohols in the presence of a base co-catalyst and optimizations were carried out in order to obtain maximum conversions. In the second instance, a series of three arene-ruthenium-carboxylato catalysts were subjected to dehydrogenation studies and the catalyst [Ru(OAc)₂(p-cymene)] operating under acidic conditions was found to be the best amongst the three. In both cases, primary alcohols were converted to the corresponding esters while secondary alcohols rendered ketones on oxidation. Particular emphasis was placed on methyl ricinoleate, a renewable fatty acid methyl ester (FAME) obtained from castor oil. The dehydrogenation of this ester furnished in high yields the saturated keto-ester methyl 12-oxostearate via a hydrogen borrowing alcohol dehydrogenation-alkene hydrogenation tandem reaction<br>Ce travail comporte deux volets de recherche indépendants qui ont pour objectifs communs de rendre certains procédés catalytiques plus efficaces et plus acceptable d'un point de vue environnemental. La première partie des travaux de thèse concerne le design et la synthèse de pré-catalyseurs du ruthénium pour la métathèse des oléfines en vue de leurs Nanofiltration (NF) en milieu organique. La nanofiltration en milieu organique est un procédé de séparation qui suscite un grand intérêt à la fois académique et industriel pour la purification de mélanges réactionnels contenant des résidus organométalliques et pour le recyclage de catalyseurs. Au cours de ce travail, plusieurs pré-catalyseurs basés sur l'architecture des complexes de type Hoveyda ont été préparés en apportant des modifications stériques et polaires sur les ligands isopropoxystyrene ou NHC. Ces complexes ont été caractérisés et leur activité catalytique en métathèse ainsi que leur nanofiltration ont été étudié. Dans une seconde partie, la déshydrogenation d'alcool sans accepteur d'hydrogène a été étudié. Dans un premier temps le complexe [RuCl₂(p-cymene) IMes] a été évalué en présence d'une base et de nombreux paramètres expérimentaux ont été optimisés. De la même manière, un autre catalyseur à ligand carboxylate [Ru(OAc)₂2(p-cymene)] et opérant en milieu acide a été étudié et s'est montré plus actif que le catalyseur précédemment cité. Dans les deux cas, les alcools secondaires ont été oxydés en cétones alors que les alcools primaires ont conduit à la formation d'esters. Une attention particulière a été apportée à la déshydrogénation du ricinoléate de méthyle, un composé renouvelable issu de l'huile de ricin. Ce substrat a pu être transformé efficacement en méthyl 12-oxostéarate, un produit à haute valeur ajoutée, par un processus tandem dit ‘d'emprunt d'hydrogène' consistant en la déshydrogénation d'alcool/hydrogénation d'alcène

Since the discovery of catalyst-transfer polymerization in 2004 there has been significant research into expanding the scope from Kumada couplings of poly-thiophenes mediated by nickel initiators. This thesis presents an investigation toward the synthesis of -conjugated polymers by the elusive pseudo-living polymerization of chloroarene monomers. Chapter 1 sets the scene with an in-depth review of chain-growth polymerizations mediated by palladium catalysts. In chapter 2, we report the first examples of exhaustive substitution of poly-chloroarenes in the presence of a deficit of nucleophile in the sp3-sp2 Negishi coupling mediated by PEPPSI-IPr. These experiments demonstrated intramolecular transfer of the active catalyst which is essential for catalyst-transfer polymerization. Chapter 3 describes the synthesis of the highly active PEPPSI-IPent precatalyst from cheap commercially available starting materials with minimal purification. Subsequently in chapter 4, it was demonstrated that PEPPSI-IPent undergoes exhaustive substitution of poly-chloroarenes in the presence of a deficit of nucleophile in sp2-sp2 Kumada, Negishi and Suzuki cross-couplings. In chapter 5, optimization of current Kumada polymerization of bromo phenylene-based monomer mediated by PEPPSI-IPr is described. Direct comparison of model reactions and Kumada polycondensation confirmed high selectivity for exhaustive substitution is required to achieve polycondensation in a chain-growth manner. Initial research into catalyst-transfer polycondensation of chloroarene monomers did not achieve polymerization in a chain-growth manner using modified conditions from bromoarene monomers.

Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2015.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references.<br>Chapters 1 - 3. A series of easily prepared, phosphine-ligated palladium precatalysts based on the 2-aminobiphenyl scaffold have been prepared. The role of the precatalyst-associated labile halide (or pseudohalide) in the formation and stability of the palladacycle has been examined. It was found that replacing the chloride in the previous version of the precatalyst with a mesylate leads to a new class of precatalysts with improved solution stability and that are readily prepared from a wider range of phosphine ligands, including the bulky, electron-rich di-tert-butylphosphino biaryl ligands. Additionally, N-methyl- and N-phenyl analogues have been prepared. These efficacy of these precatalysts were examined in a broad range of C-C, C-N, and C-O bond-forming reactions. Chapter 4. The intramolecular hydroalkylation of di- and trisubstituted alkenes bearing a pendant alkyl bromide to form stereodefined (hetero)carbocycles is reported. The system is highly regio- and stereoselective and employs a Cu-DTBM-SEGPHOS catalyst and (dimethoxy)methylsilane as the stoichiometric reductant. This intramolecular hydroalkylation reaction provides facile access to a multitude of ring systems and its utility is further demonstrated in the enantioselective synthesis of paroxetine.<br>by Nicholas C. Bruno.<br>Ph. D. in Organic Chemistry

The development of a synthetic approach to 2,5-unsymmetrically substituted piperazines from readily available terminal alkynes and amine substrates employing both intermolecular and intramolecular hydroamination methodologies developed in the Schafer group is reported in this thesis. The approach requires only three isolation/purification protocols. Firstly, regioselective intermolecular hydroamination in the presence of titanium bis(amidate) precatalyst is performed, followed by the one-pot addition of trimethylsilyl cyanide to the imine and subsequent displacement of the TMS group to obtain α-aminonitriles. Reduction of the α-aminonitriles is required to achieve the desired hydroamination precursors. The piperazine core is then completed by intramolecular diastereoselective hydroamination with the zirconium tethered bis(ureate) catalyst. The synthetic approach employed features two hydroamination reactions for the synthesis of these biologically active heterocycles. Synthesis of enantiopure piperazine was achieved via a chiral auxiliary-based approach; after the enantiopure aminonitrile was synthesized, subsequent reduction and enantiospecific intramolecular hydroamination with the zirconium tethered bis(ureate) catalyst were performed. The synthetic sequence thus developed illustrates the usefulness of inexpensive and low-toxicity group 4 amidate and ureate catalysts for the rapid synthesis of functionalized heterocycles suitable for further medicinal chemistry investigations. The screening of a series of novel unsymmetrically substituted piperazines for calcium channel blocking activity was performed. Potent N-type calcium channel blockers were discovered and a new trend in the development of piperazine medicinally relevant heterocycles was found. This contribution highlights a modular synthetic approach to the efficient preparation of previously unknown piperazines suitable for biological screening. In addition to 2,5-disubstituted piperazines, 2,5-disubstituted diazepanes were efficiently obtained on the basis of the developed strategy. Specific heterocyclic structural features in the 1H NMR spectra inspired us to propose a practical NMR-based method for revealing the relative stereochemical configuration of the synthesized heterocycles. Overall, this thesis covers different aspects of medicinal chemistry, green chemistry, synthetic chemistry and catalysis to provide conceptual and practical contributions to each of these branches of modern chemistry. Concepts and protocols developed in the course of this thesis can bring an important contribution to new approaches in drug discovery and our understanding of the application of hydroamination in synthetic chemistry.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2019<br>Cataloged from PDF version of thesis. Page 393 blank.<br>Includes bibliographical references.<br>[color illustrations] We introduce a new class of bench-stable N-heterocyclic carbene nickel precatalysts for homogeneous nickel-catalysis. The nickel(II) complexes are readily activated to Ni⁰ in situ under mild conditions, via a proposed Heck-type mechanism. The precatalysts are able to facilitate carbonyl-ene, hydroalkenylation, and amination reactions. [color illustrations] Herein, we report the synthesis and characterization of a new class of air- and moisture-stable triphenylphosphine nickel(II) precatalysts, which activate through a Heck-type mechanism. The activity of these precatalysts is demonstrated with a carbonyl-ene coupling reaction.<br>by Jessica M. Weber.<br>Ph. D.<br>Ph.D. Massachusetts Institute of Technology, Department of Chemistry

Carbon-carbon bond formation is one of the most important reactions in organic chemistry, and the Suzuki-Miyaura cross-coupling reaction has become a forerunner in this area. Considerable research has been directed at the mechanistic aspects and synthetic utility of the reaction; however, little attention has been given to the formation of the putative PdL2 catalysts. Due to their high reactivities, these catalysts are typically difficult to store and therefore are often generated in situ in unknown yields and at unknown rates via any number of available palladium precursors. This thesis describes research directed towards determining the optimum conditions to quantitatively generate compounds of the type Pd(0)Ln (L = PMePh2, PPh3, PCy3, PMeBut2, PBut3, dppe, dppp, dppf) from Pd(h5-C5H5)(h3-1-Ph-C3H4). Pd(h5-C5H5)(h3-1-Ph-C3H4) has been found to be a superior precursor for synthesizing catalytically active PdL2 compounds due to its ease in handling and reactivity with tertiary phosphines. Furthermore, investigations into the role of water in the transmetallation step of the Suzuki-Miyaura reaction are presented. The research indicates that water is necessary to effect the transmetallation step when coupling [NBu4][PhBF3] with 4-bromotoluene in toluene; however, the amount of water above one equivalent has no significant effect on the rate or yield of the reaction.<br>Thesis (Master, Chemistry) -- Queen's University, 2009-07-23 12:57:10.248

There has been considerable interest over the past decade in the preparation and applications of copolymers of ethylene with functionalized polar olefins. Such copolymers are expected to exhibit a variety of potentially very useful properties such as paintability, adhesion to polar surfaces, and miscibility with polar polymers such as polyesters and polyamides, but there are limitations associated with producing copolymers of ethylene with polar monomers via Ziegler-Natta processes. Many classes of Ziegler-Natta catalysts, especially those of the early transition metals (Ti and Zr), are highly oxophilic and hence are poisoned by functionalities such as -OH groups. This problem can in principle be alleviated by implementing the use of protecting groups such as –OSiMe3, which has previously been shown to be an effective masking agent both for steric reasons and because O-Si π bonding decreases the Lewis basicity of the ether oxygen atom. One can also utilize late transition metal catalyst systems, which are generally less Lewis acidic and therefore less susceptible to poisoning by functional groups. In this thesis the results of an investigation of the copolymerization of ethylene with CH2=CH(CH2)nOSiMe3 (n = 1, 2, 8) will be presented. We have been using MAO activated dibromo[1,4-bis(2,6-diisopropylphenyl)acenaphthenediimine]nickel(II) (D) as catalyst, as this system is known to produce reasonably linear polyethylene and hence may be expected to produce essentially LLDPE containing –(CH2)nOSiMe3 branches. The latter can be hydrolyzed to give polar –(CH2)nOH branches.<br>Thesis (Master, Chemistry) -- Queen's University, 2009-01-31 14:43:09.93

In this study, an attempt was made to identify the electronic and steric properties of the precatalyst ligands that determine the characteristics of phosphine ligated Grubbs-type precatalysts for alkene metathesis by means of molecular modelling. It was found from studying the literature that the possibilities for synthesising a wide range of phosphine ligands are almost unlimited. Additionally, it was found that there is no easy method to determine the electronic and steric properties of the precatalyst ligands in existence. Molecular modelling might provide a method to study potential ligands and precatalysts before tedious synthesis methods are attempted. It was found that the theoretically calculated structures of the commercially available precatalysts compared well with the experimental data reported in literature. It is also shown that the energy profiles for alkene metathesis of simplified model systems do not compare well with non-simplified systems. Correlations between these simplified model systems and experimental work have to be regarded as serendipitous at best. When the energy profiles of the various new and commercially available precatalysts are compared, similarities in the energy trends for 1-octene metathesis are observed. These similarities raise questions about the significance of the differences in the energy barriers. In an effort to better understand this, two low activity precatalysts were also investigated in an attempt to identify the area or trend of poor catalysis. Instead of providing the desired different result, trends very similar to that of the highly active precatalysts were observed. This led to the observation that, without a sufficiently large dataset, great care should be taken before conclusions are drawn from theoretical work. Since the electronic investigation did not provide the desired result of finding a fast and effective method of determining which ligand merits further investigation, some steric aspects were studied. Once again, the precatalysts proved to be remarkably similar and no definitive answer for the observed differences in the various precatalysts could be determined. A preliminary experimental study into the feasibility of the synthesis of the new potential ligands was done. The multi-step synthesis route resulted in low yields in some cases, with the need for large volumes of solvents to purify the products. The toxicity of phenylphosphine also has to be taken into account when considering these types of ligands. A new precatalyst obtained by using a new ligand should show a remarkable improvement over the current commercially available precatalysts to justify the additional cost to synthesise a new ligand. It would seem that for future projects more consideration should be given to the deactivation mechanism of the Grubbs-type precatalysts, since this seems to be the logical starting point to look for the answers to the experimentally observed differences. A deeper understanding of the mechanism of alkene metathesis can only be obtained if all aspects are investigated in as much detail as possible. While the results did not provide the initially expected outcome, some valuable insights were gained that challenge the current way of thinking about the alkene metathesis mechanism. It is also clear that to oversimplify a very complex reaction and using limited data will lead to false assumptions being made.<br>PhD (Chemistry), North-West University, Potchefstroom Campus, 2014

This thesis focuses on the exploration of a new titanium complex for the hydroamination of alkynes/alkenes. A new pentafluoro amide proligand, [HNC4H9CO( CeF5)] 5, and two related bis(amidate)titanium-bis(amido) complexes (8 and 9) were designed, prepared and fully characterized by multinuclear NMR spectroscopy, mass spectrometry, elemental analysis and X-ray crystallography. Both intramolecular and intermolecular hydroamination of alkynes were investigated using the bis(amidate)titanium-bis(amido) complexes as catalysts. Preliminary results were obtained from NMR tube scale reaction monitored by ' H NMR spectroscopy using an internal standard. Larger scale intermolecular hydroamination reactions followed by LAH/THF reduction were carried out to give corresponding isolated amines in yields comparable to that of the NMR tube scale reaction. Hydroamination of.alkenes using these precatalysts was unsuccessful. Compared with other reported titanium complexes, our precatalysts demonstrated better or comparable hydroamination reactivity. Based on literature reports, a mechanism was proposed for the bis(amidate)titanium complex-catalyzed hydroamination which was further verified by preparation of catalytically active intermediates. Stoichiometric reactions of precatalysts with bulky primary amines indicated formation of a titanium imido complex, the active species for hydroamination. Titanium imido complexes or pyridine-trapped imido complexes were isolated and characterized by multinuclear NMR spectroscopy and mass spectrometry. In one case a pyridine-trapped imido complex shows higher reactivity than the corresponding bis(amidate) precatalyst. However, the stoichiometric reaction between precatalysts and less bulky amines form titanium imido dimers, explaining This thesis focuses on the exploration of a new titanium complex for the hydroamination of alkynes/alkenes. A new pentafluoro amide proligand, [HNC4H9CO( CeF5)] 5, and two related bis(amidate)titanium-bis(amido) complexes (8 and 9) were designed, prepared and fully characterized by multinuclear NMR spectroscopy, mass spectrometry, elemental analysis and X-ray crystallography. Both intramolecular and intermolecular hydroamination of alkynes were investigated using the bis(amidate)titanium-bis(amido) complexes as catalysts. Preliminary results were obtained from NMR tube scale reaction monitored by ' H NMR spectroscopy using an internal standard. Larger scale intermolecular hydroamination reactions followed by LAH/THF reduction were carried out to give corresponding isolated amines in yields comparable to that of the NMR tube scale reaction. Hydroamination of.alkenes using these precatalysts was unsuccessful. Compared with other reported titanium complexes, our precatalysts demonstrated better or comparable hydroamination reactivity. Based on literature reports, a mechanism was proposed for the bis(amidate)titanium complex-catalyzed hydroamination which was further verified by preparation of catalytically active intermediates. Stoichiometric reactions of precatalysts with bulky primary amines indicated formation of a titanium imido complex, the active species for hydroamination. Titanium imido complexes or pyridine-trapped imido complexes were isolated and characterized by multinuclear NMR spectroscopy and mass spectrometry. In one case a pyridine-trapped imido complex shows higher reactivity than the corresponding bis(amidate) precatalyst. However, the stoichiometric reaction between precatalysts and less bulky amines form titanium imido dimers, explaining

<p>The first half of this thesis details the synthesis and coordination chemistry of a very unusual pyridine-linked bis(secondary phosphine) pincer ligand system. Despite the highly nucleophilic phosphide donors, this dianionic system is an unexpectedly poor pincer ligand. Crystallographic and DFT studies reveal that both phosphide-metal σ- and π-bonding is compromised by long metal-phosphorus bonds, which result in significant distortions to the chelate ring. The neutral ligand coordinates readily κ² (via phosphines) to late metals, such as palladium(II), affording P-chirogenic diastereomers. Crystallographic and spectroscopic analysis of a series of palladium(II) dihalides stabilized by this bis(phosphine) indicate that one diastereomer is enthalpically favored, while the other more structurally versatile diastereomer is favored entropically. There is also evidence of an interesting phosphine epimerization pathway assisted by the non-coordinated pyridine ring.</p> <p>Ethylene polymerization and ethylene/1-hexene copolymerization activities of several zirconium(IV) and vanadium(III) polymerization precatalysts supported by heterocycle-linked bis(phenolate) ligands are also discussed. Activities as high as 106 g PE/(mol x h) were observed, but only the vanadium catalyst incorporates comonomer, albeit with low efficiency (&lt;1 mol%).</p> <p>Finally, catalytic applications of air- and water-tolerant bis(μ-hydroxy) palladium(II) dimers have been investigated. Mechanistic studies show that this precatalyst can oxygenate olefins via a Wacker-type mechanism upon dimer dissociation. In the absence of stoichiometric oxidant, the resulting palladium(II) hydride intermediate can then isomerize and oligomerize olefins with turnover numbers at room temperature as high as 2100/h and 600/h, respectively. We also show that the catalyst is insensitive to water and air, so that olefin isomerization and oligomerization can be carried out on the benchtop in the absence of activators. In the presence of excess tert-butylhydroperoxide, Wacker-type behavior is favored, and neither isomerization nor oligomerization is observed. These dimers can also catalyze the aerobic dehydrogenation of cyclohexene to benzene with relatively low turnover numbers (1/h). Nevertheless, mechanistic studies indicate a C-H activation/β-hydride elimination sequence that does not involve an allylic-activated species.</p>

Since the development of the ruthenium containing precatalysts Grubbs 1 (1) and Grubbs 2 (2), there was an increase in the development of new precatalysts. The NMR characterization could not cope with this. The NMR characterization mainly consists of 1H, 31P, COSY and rarely 13C. Due to the high natural abundance of 1H and 31P (99.98% and 100%), these experiments could be carried out quickly and easily. The only change that had to be made was to the spectral width, to accommodate the carbene signal (Ru=CH) between δ 20.02 and δ 17.32 ppm. The lack of 13C characterization is attributed to the low natural abundance of these nuclei that is only 1.10% and the lack of published parameters. Furthermore, the broad spectral width of 300 ppm increases the difficulty because the number of scans has to be increased to increase the sensitivity of the spectra and obtain useful data. In this study the precatalyst 1 was used to learn the NMR technique as well as to acquire the NMR parameters. 2 and two other commercial Grubbs-type precatalysts 3 and 4 underwent NMR characterization so that acquired values could be compared with the literature. Six other non-commercial Grubbs-type precatalysts 5-10 were synthesized and characterized. Due to the instability of the precatalysts and taking into account the duration of these experiments, the characterization was done over three steps. The first step was to do the following experiments: 1H, COSY, HSQC and HMBC, which took four hours. The next step was the DEPT135 experiment of three hours, and finally the 13C experiment of seven hours. The maximum amount of information could be obtained in this way. The combined NMR parameters for this study was obtained and used to characterize the Grubbs-type precatalysts 5-10 partially. Due to the large amount of overlapping peaks in the aromatic and alkane areas the resolution was not sufficient for full characterization.<br>MSc (Chemistry), North-West University, Potchefstroom Campus, 2014