<p>Allylic amines are important and fundamental building blocks due to their wide-spread occurrence in many natural products and the ability to further functionalize them by transformations on the double bond to generate a diverse range of compounds. Transition-metal catalyzed allylic substitution represents an attractive and efficient approach towards the synthesis of these allylic amines. However, limitations associated with the traditional methods developed for such allylic amination in terms of regiospecificity, atom economy and generality in these transformations, combined with the importance of allylic amination, prompted us to develop novel atom efficient and regiospecific methods for their synthesis.</p><p>A 1:1 mixture of AuCl[P(<italic>t</italic>-Bu)₂<italic>o</italic>-biphenyl] (5 mol %) and AgSbF₆ (5 mol %) catalyzed the intermolecular amination of underivatized allylic alcohols with 1-methyl-2-imidazolidinone and related nucleophiles. The first examples of intermolecular allylic amination was developed that in the case of gamma-unsubstituted and gamma-methyl-substituted allylic alcohols, occurred with high gamma-regioselectivity and <italic>syn</italic>-stereoselectivity.</p><p>A 1:1 mixture of AuCl[P(<italic>t</italic>-Bu)₂<italic>o</italic>-biphenyl] (5 mol %) and AgSbF₆ (5 mol %) also served as a very efficient catalytic system for the intramolecular amination of allylic alcohols with alkylamines to form substituted pyrrolidine and piperidine derivatives. The protocol was effective for a range of secondary as well as primary alkylamines as nucleophiles with different substitutions on the alkyl chain tethering the nucleophile to the allylic alcohol. The method was also extended towards the total synthesis of the naturally occurring alkaloid (S)-(+)-coniine in two steps from the starting (R,Z)-8-(N-benzylamino)-3-octen-2-ol. In addition, gold(I)-catalyzed cyclization of (R,Z)-8-(N-benzylamino)-3-octen-2-ol (96% ee) led to isolation of (R,E)-1-benzyl-2-(1-propenyl)piperidine in 99% yield and 96% ee that established the net syn-addition of the nucleophile with respect to the departing hydroxyl group.</p><p> A bis(gold) phosphine complex (S)-Au₂Cl₂(DTBM-MeOBIPHEP) (2.5 mol %) and AgClO₄ (5 mol %) catalyzed the intramolecular enantioselective dehydrative amination of allylic alcohols with carbamates to form the corresponding substituted pyrrolidines, piperidines, morpholines and piperazines in excellent yields and with up to 95% ee. This general and effective protocol tolerated a range of carbamates as well as sulfonamides as nucleophiles. Cyclization of chiral amino allylic alcohols that possessed a stereogenic homoallylic or hydroxy-bound carbon atom occurred with an overriding catalyst control of asymmetric induction. In addition, stereochemical analysis of the cyclization of a chiral non-racemic secondary allylic alcohol established the net syn-displacement of the hydroxy group by the carbamate nucleophile.</p><p>Alongside allylic amination, a cationic gold(I)-N-heteocyclic carbene complex catalyzed the intermolecular etherification (alkoxylation) of allylic alcohols in a regiospecific and syn-stereoselective fashion. The transformation was highly efficient to utilize unactivated primary and secondary alcohols as nucleophiles with different allylic alcohols to undergo regiospecific etherification. Employment of a chiral nonracemic secondary allylic alcohol, trans-5-(benzyloxy)pent-3-en-2-ol (98% ee) showed a high level of chirality transfer on reaction with n-butanol to the corresponding allylic ether, (2-butoxypent-3-en-1-yloxy)methylbenzene (97% ee) and established the net syn-addition of the alcohol nucleophile with respect to the departing hydroxyl group of the allylic alcohol.</p> / Dissertation

A series of cationic Rh(I) diphosphine and phosphine-alkene complexes have been isolated and fully characterised. The reactivity of these species towards hydrogenation, dehydrogenation and dehydrocoupling reactions has been investigated. The use of potentially hemilabile ligands DPEphos and XANTphos in the intramolecular dehydrogenation chemistry of tricyclopentylphosphine is reported. The comparison in reactivity of these isolated diphosphine phosphine-alkene complexes towards hydrogenation and with acetonitrile is discussed along with their ability to dehydrocouple secondary silane, Ph₂SiH₂, and amine-borane H₃B·NMe₂H. The acceptorless dehydrogenation of a tethered cyclopentane with cationic Rh(I) diphosphine complexes has also been extended to include thioethers. Isolated cationic Rh(I) phosphine-alkene complexes with labile fluorobenzene ligands are found to act as a source of the reactive 12-electron [Rh{PR₂(ƞ²-C₅H₇)}]+ (R = cyclopentyl (Cyp)/ iPr) fragment in solution and can coordinate two amine-borane ligands (either H₃B·NMe₃, H₃B·NMe₂H or H₃B·NMeH₂) in a novel and unique bis-σ-binding mode. The catalytic activity of some of these isolated complexes in the dehydrocoupling of H₃B·NMe₂H and H₃B·NMeH₂ has been determined. With a view to further understanding the mechanism of catalytic transition metal assisted amine-borane dehydrogenation and dehydrocoupling, known B-N intermediates H₃B·NMe₂BH₂·NMe₂H and [H₂B·NMeH]₃ were also coordinated to the [Rh{PCyp₂(ƞ²-C₅H₇)}]+ fragment and investigated with regard to their role in the catalytic cycle. Structure activity relationships determined from stoichiometric reactions of cationic Rh(I) diphosphine fluorobenzene complexes with amine-boranes enabled the design of a highly efficient homogeneous catalyst capable of dehydrogenating H₃B·NMe₂H to [H₂BNMe₂]₂ at 0.2 mol% loading in 30 minutes at 298 K. Rapid dehydrogenation and dehydrocoupling of H₃B·NMeH₂ to form high molecular weight poly(N-methylaminoborane) with a low PDI has also been achieved. Investigations using model aminoborane H₂B=NiPr₂ and intermediate B-N species H₃B·NMe₂BH₂·NMe₂H and [H₂B·NMeH]₃ has helped establish an overall mechanistic rationale for this process.

In the following thesis, new methodologies towards the synthesis of a range of sulfonyl (-SO₂-) containing functional groups are documented. These methods utilise easy-to-handle sulfur dioxide surrogates, such as DABSO (vide infra), and exploit palladium catalysis as a new mechanistic protocol for the incorporation of the -SO2- unit. <b>Chapter 1</b> is a literature review surveying sulfur dioxide in organic synthesis, the established uses of SO₂ surrogates and the importance of the sulfonyl moiety in chemistry. Palladium-catalysed (carbonylative) cross-couplings are also broadly discussed as they provide inspiration for, and mechanistic similarities with, the proposed chemistry. <b>Chapter 2</b> describes a de novo synthesis of the sulfonamide functional group; a three-component and convergent methodology coupling (hetero)aryl and alkenyl halides with sulfur dioxide (provided by easy-to-handle surrogates such as DABSO) and hydrazine nucleophiles, is documented. This is achieved through the action of a readily available palladium catalytic system and is the first example of a metal-catalysed sulfonylative cross-coupling of halide based electrophiles. <b>Chapter 3</b> presents a new method of generating (hetero)aryl and alkenyl sulfones. The ability of organometallic reagents to add to sulfur dioxide (supplied via DABSO) is applied to deliver the corresponding metal sulfinate salt. This in situ derived sulfinate is coupled with an (hetero)aryl or alkenyl (pseudo)halide using palladium catalysis to form the desired sulfone. An electronically modified XantPhos-type ligand was designed for the reaction in order to suppress unwanted aryl-aryl exchange. <b>Chapter 4</b> documents the generation of (hetero)aryl and alkenyl sulfinates from the corresponding halide and DABSO through a palladium-catalysed sulfination protocol, obviating the need for organometallic reagents. A mild set of conditions using IPA as both a solvent and reductant together with a low loading of palladium catalyst offers an attractive route to sulfonyl compounds thanks to the in situ derived sulfinates being converted into a broad variety of functional groups via established onwards reactivity. <b>Chapter 5</b> discusses the conclusion of the research and the potential for future work. <b>Chapter 6</b> presents the experimental data.

This thesis discusses the intermolecular hydroacylation reaction using cationic rhodium bis- phosphine complexes as catalysts. A series of small bite-angle rhodium bis-phosphine complexes have been prepared and characterised. The reactivity of these complexes has been investigated in order to gather information about the effect of subtle changes in the ligand design and they are compared to the previously reported catalysts. Chapter 2 presents the challenges involved in the synthesis of small bite-angle isopropyl and cyclohexyl PNP and PCP bis-phosphine ligand containing rhodium complexes. These complexes have been fully characterised and screened in intermolecular hydroacylation reaction using 2- (methylthio)benzaldehyde (<strong>E</strong>) and 1-octene or 1-octyne as substrates. The formed complexes were shown to be very efficient and regioselective alkyne hydroacylation catalysts. The mechanism of the hydroacylation reaction was investigated using the isopropyl PNP complex [Rh(ⁱPrPNMePⁱPr₂)(C₆H₅F)][BAr^F₄] (<strong>11b</strong>). Chapter 3 concentrates on developing new rhodium bis-phosphine complexes that involve a ligand incorporating the small bite-angle motif with the one of hemilability. The PNP complex [Rh((2-OMe-C₆H₄)₂PNMeP(2-OMe-C₆H₄)2)(C₆H₅F)][BAr^F₄] (<strong>41</strong>) was synthesised and analytically characterised. <strong>41</strong> was shown to be an active alkyne hydroacylation catalyst with more stability towards the catalyst deactivation pathway, reductive decarbonylation, compared to the previously investigated <strong>11b</strong>. Additionally mechanistic studies using <strong>41</strong> were carried out. The final chapter moves on to study the C-S activation ability of small bite-angle rhodium bis- phosphine complexes to remove the sulfur tether from the hydroacylation products at the end of the hydroacylation reaction. A screening is conducted to compare the reactivity of different small bite-angle ligands. Additionally, a detailed investigation is carried out to see the effect the C-S activation has on the hydroacylation reaction.

The main focus of the present work is the recovery process for spent fuels based on catalytic hydrogenation of liquid organic hydrides (LOH). To gain the knowledge about the possible hurdles of hydrogen loading process, the hydrogenation of 9-ethylcarbazole as a model compound was elected to be studied in more detail. The structures of the intermediates and products of this reaction were characterized for the first time using combined GC-MS and NMR analysis with reference to DFT calculations. The fully saturated product was found to be a mixture of stereoisomers. A reaction model was developed which agreed well with the experimental results. The combined theoretical and experimental approaches were also undertaken to identify catalytic sites on the metal surface and their role in the hydrogenation of 9-ethylcarbazole. Kinetically stable intermediate (Plus 8 [H]) containing a central unsaturated “pyrrole” ring was found to be accumulated in the solution over a ruthenium black catalyst. Its further hydrogenation was found to involve its unusual shuttling from terraced sites to higher indexed sites. The stability of Plus 8 [H] was found to be influenced by the type of active sites present on the surface of the catalyst, as well as by the electronic structure of the metal. In addition, the kinetics of the hydrogenation was analyzed experimentally and the activation energies were obtained for all of the intermediate steps. Further understanding of how the molecules interact with the catalyst surface was provided by examining the hydrogenation activity and selectivity of a series of LOH. The general factors involved in LOH structure- catalyst –activity trend were outlined. Overall, due to a number of defined challenges in the LOH spent fuel recharging, it is believed that this complex H2 storage strategy is not likely to meet the targets for wide scale applications.

Catalysis is one of the pillars of the chemical industry. While the use of catalyst is typically recognized in the automobile industry, their impact is more widespread as; catalysts are used in the synthesis of 80% of the US commercial chemicals. Despite the improved selectivity provided by catalyst, process inefficiencies still threaten the sustainability of a number of synthesis methods, especially in the pharmaceutical industry. Recyclable solid supported catalysts offer a unique opportunity to address these inefficiencies. Such systems coupled with continuous synthesis techniques, have the potential to significantly reduce the waste to desired product ratio (E-factor) of the production techniques. This research focuses developing sustainable processes to synthesize organic molecules by using continuous synthesis methods. In doing so, solid supported metal catalyst systems were identified, developed, and implemented to assist in the formation of carbon-carbon bonds. Newly developed systems, which utilized metal nanoparticles, showed reactivity and recyclability, comparable to commercially available catalyst. Nanoparticles are emerging as useful materials in a wide variety of applications including catalysis. These applications include pharmaceutical processes by which complex and useful organic molecules can be prepared. As such, an effective and scalable synthesis method is required for the preparation of nanoparticle catalysts with significant control of the particle size, uniform dispersion, and even distribution of nanoparticles when deposited on the surface of a solid support. This project describes the production of palladium nanoparticles on a variety of solid supports and the evaluation of these nanoparticles for cross coupling reactions. This report highlights novel synthesis techniques used in the formation of palladium nanoparticles using traditional batch reactions. The procedures developed for the batch formation of palladium nanoparticles on different solid supports, such as graphene and carbon nanotubes, are initially described. The major drawbacks of these methods are discussed, including limited scalability, variation of nanoparticle characteristics from batch to batch, and technical challenges associated with efficient heating of samples. Furthermore, the necessary conditions and critical parameters to convert the batch synthesis of solid supported palladium nanoparticles to a continuous flow process are presented. This strategy not only alleviates the challenges associated with the robust preparation of the material and the limitations of scalability, but also showcases a new continuous reactor capable of efficient and direct heating of the reaction mixture under microwave irradiation. This strategy was further used in the synthesis of zinc oxide nanoparticles. Particles synthesized using this strategy as well as traditional synthesis methods, were evaluated in the context industrially relevant applications.

No description available.

Reductive functionalization of methyl ligands by 3d metal catalysts and two possible side reactions has been studied. Selective oxidation of methane, which is the primary component of natural gas, to methanol (a more easily transportable liquid) using organometallic catalysis, has become more important due to the abundance of domestic natural gas. In this regard, reductive functionalization (RF) of methyl ligands in [M(diimine)2(CH3)(Cl)] (M: VII (d3) through CuII (d9)) complexes, has been studied computationally using density functional techniques. A SN2 mechanism for the nucleophilic attack of hydroxide on the metal-methyl bond, resulting in the formation of methanol, was studied. Similar highly exergonic pathways with very low energy SN2 barriers were observed for the proposed RF mechanism for all complexes studied. To modulate RF pathways closer to thermoneutral for catalytic purposes, a future challenge, paradoxically, requires finding a way to strengthen the metal-methyl bond. Furthermore, DFT calculations suggest that for 3d metals, ligand properties will be of greater importance than metal identity in isolating suitable catalysts for alkane hydroxylation in which reductive functionalization is used to form the C—O bond. Two possible competitive reactions for RF of metal-methyl complexes were studied to understand the factors that lower the selectivity of C—O bond forming reactions. One of them was deprotonation of the methyl group, which leads to formation of a methylene complex and water. The other side reaction was metal-methyl bond dissociation, which was assessed by calculating the bond dissociation free energies of M3d—CH3 bonds. Deprotonation was found to be competitive kinetically for most of the 1st row transition metal-methyl complexes (except for CrII, MnII and CuII), but less favorable thermodynamically as compared to reductive functionalization for all of the studied 1st row transition metal complexes. Metal-carbon bond dissociation was found to be less favorable than the RF reactions for most 3d transition metal complexes studied. The first dinitrogen dicopper (I) complex has been characterized using computational and experimental methods. Low temperature reaction of the tris(pyrazolyl)borate copper(II) hydroxide {iPr2TpCu}2(µ-OH)2 with triphenylsilane under a dinitrogen atmosphere gives the µ -N2 complex, {iPr2TpCu}2(µ -N2). X-ray crystallography reveals an only slightly activated N2 ligand (N-N: 1.111(6) Å) that bridges between two iPr2TpCuI fragments. While DFT studies of mono- and dinuclear copper dinitrogen complexes suggest a weak µ-backbonding between the d10 CuI centers and the N2 ligand, they reveal a degree of cooperativity in the dinuclear Cu-N2-Cu interaction.

<div>Cyclopropanes are commonly found throughout synthetic and natural biologically active compounds. The Simmons–Smith cyclopropanation reaction is one of the most useful methods for converting an alkene into a cyclopropane. Zinc carbenoids are the active intermediate in the reaction, capable of delivering the methylene unit to a broad variety of substrates. Significant advances have been made in the field to increase overall efficiency of the reaction including the use of diethyl zinc as a precursor and allylic alcohols as directing groups.</div><div>Despite the many notable contributions in zinc carbenoid chemistry, persistent limitations of the Simmons–Smith reaction still exist. Zinc carbenoids exhibit poor steric discrimination in the presence of a polyolefin with minimal electronic bias. Additionally, due to the electrophilic nature of zinc carbenoid intermediates, the reaction performs inefficiently with electron-deficient olefins. Finally, alkyl-substituted zinc carbenoids are known to be quite unstable, limiting the potential for substituted cyclopropanation reactions.</div><div>In this work, we demonstrate that cobalt catalysis can be utilized to access novel cyclopropane products through the activation of dihaloalkanes. The content of this thesis will focus on the limitations of Zn carbenoid chemistry and addressing them with cobalt catalyzed, reductive cyclopropanations. In addition to this reactivity, we also demonstrate the dimethylcyclopropanation of activated alkenes to furnish valuable products applicable to natural product synthesis and pharmaceutically relevant compounds. Finally, we will show the unique character of the cobalt catalyzed cyclopropanation reaction through mechanistic experiments and characterization of reaction intermediates. In whole, these studies offer a complementary method to zinc carbenoid chemistry in producing novel and diverse cyclopropane products.</div>

No description available.