The main objective of the research described in this dissertation was the preparation of a range of bulky and electron-rich phosphine ligands using the DoM methodology developed in our labs for this purpose. These ligands would be employed in the Suzuki cross-coupling reaction of deactivated aryl bromides and aryl chlorides. Initially, a range of phosphinic amides was synthesised and tested for DoM reactivity. TMSCl, MeI and O2 were successfully used as electrophiles, incorporating TMS, Me and OH groups in the ortho-position of these phosphinic amide systems. This development was encouraging and provided a route to incorporate a phosphine on the ortho-position of these phosphinic amide systems by using Ph2PCl and Cy2PCl as electrophiles to incorporate Ph2P and Cy2P, respectively. The route was versatile and a range of electrophiles was used to prepare phosphine ligands with varying electronic and steric properties. These electrophiles (of the R2PCl variety) were often specifically prepared from PCl3 and the corresponding Grignard reagent. Phosphine ligands synthesised in this research project using our DoM (directed ortho metallation) methodology were tested in Suzuki cross-coupling reactions of deactivated aryl bromides and some aryl chlorides and showed excellent reactivity, with the advantage that the ligands of this study are oxidatively and hydrolytically stable. Efforts were also made to modifying the phosphinic amide-functionalised phosphine ligands to generate their water-soluble derivatives. One way of achieving this was by the hydrolysis of the phosphinic amide moiety to the phosphinic acid analogue. Salts of these phosphinic acid derivatives have promising activities as water-soluble substrates. This route was successful only iii with less electron-rich systems providing an opening for more research in this regard. In an alternative synthetic route to polar water-soluble phosphines it was envisioned that phosphonate-derivatised phosphines would offer access to water-soluble phosphine ligands by using milder hydrolysis conditions. These phosphonate systems were also tested for DoM reactivity and showed promising reactivity. Phosphonates have not previously being employed as DoM groups, and this alone expands the application and potential scope of P-based DoM groups. / Prof. D.B.G. Williams

Ph.D. (Chemistry) / Please refer to full text to view abstract

Computational techniques were employed to investigate pathways that would improve the properties and characteristics of transition metal (i.e., ruthenium) catalysts, and to explore their mechanisms. The studied catalytic pathways are particularly relevant to catalytic hydroarylation of olefins. These processes involved the +2 to +3 oxidation of ruthenium and its effect on ruthenium-carbon bond strengths, carbon-hydrogen bond activation by 1,2-addition/reductive elimination pathways appropriate to catalytic hydrogen/deuterium exchange, and the possible intermediacy of highly coordinatively unsaturated (e.g., 14-electron) ruthenium complexes in catalysis. The calculations indicate a significant decrease in the Ru-CH3 homolytic bond dissociation enthalpy for the oxidation of TpRu(CO)(NCMe)(Me) to its RuIII cation through both reactant destabilization and product stabilization. This oxidation can thus lead to the olefin polymerization observed by Gunnoe and coworkers, since weak RuIII-C bonds would afford quick access to alkyl radical species. Calculations support the experimental proposal of a mechanism for catalytic hydrogen/deuterium exchange by a RuII-OH catalyst. Furthermore, calculational investigations reveal a probable pathway for the activation of C-H bonds that involves phosphine loss, 1,2-addition to the Ru-OH bond and then reversal of these steps with deuterium to incorporate it into the substrate. The presented results offer the indication for the net addition of aromatic C-H bonds across a RuII-OH bond in a process that although thermodynamically unfavorable is kinetically accessible. Calculations support experimental proposals as to the possibility of binding of weakly coordinating ligands such as dinitrogen, methylene chloride and fluorobenzene to the "14-electron" complex [(PCP)Ru(CO)]+ in preference to the formation of agostic Ru-H-C interactions. Reactions of [(PCP)Ru(CO)(1-ClCH2Cl)][BAr'4] with N2CHPh or phenylacetylene yielded conversions that are exothermic to both terminal carbenes and vinylidenes, respectively, and then bridging isomers of these by C-C bond formation resulting from insertion into the Ru-Cipso bond of the phenyl ring of PCP. The QM/MM and DFT calculations on full complexes [(PCP)(CO)Ru=(C)0,1=CHPh]+ and on small models [(PCP')(CO)Ru=(C)0,1=CH2]+, respectively, offered data supportive of the thermodynamic feasibility of the suggested experimental mechanisms and their proposed intermediates.

A field in bloom: photoredox catalysis has allowed chemists access to highly reactive intermediates via the photo-mediated excitation of transition metal complexes and organic dyes for the mild generation of free radicals. These complexes and dyes are designed based on Nature’s blueprints of light-harvesting biomolecules that transform solar energy (photons) into chemical energy during photosynthesis. Light-mediated chemical activation is regarded as one of the most sustainable forms of chemical activation being that the energy provided by the sun is considered renewable and largely underutilized and presents an attractive avenue for research and development of new transformations that are mild, efficient, and waste-limiting in organic synthesis. Radical chemistry and photochemistry are united in their inherent ability to undergo single (or photoinduced) electron transfers by one-electron reaction modes. Combining these unique fields, photoredox catalysis has emerged as a mild and efficient alternative to classic alkyl radical generation using hazardous initiators and organostannanes. Photoredox catalysis has been dominated by ruthenium- and iridium-based polypyridyl complexes. These complexes are limited by their inherent redox potentials, restricting their reactivity towards relatively activated bonds. Nonactivated bromoalkanes and arenes are considered challenging substrates to engage using redox chemistry and typically only accessible in the realm of organostannane chemistry. Described herein are the efforts towards the discovery of free radical based organic transformations derived from nonactivated bromoalkanes and arenes mediated by photochemical excitation of polynuclear gold(I) complexes as photoredox catalysts. This work represents some of the first uses of a photoredox catalyst in the reduction of substrates having such high reduction potentials and offers a practical and useful alternative to classic radical reactions mediated by initiators (peroxides, persulfates, and azo compounds) and toxic organostannanes (Bu3SnH). Using gold based photoredox catalysts, the research conducted has provided many methodological advancements for the mild and efficient formation of carbon-carbon bonds using nonactivated bromoalkanes and a large collection of radical acceptors. Establishing the use of these photoexcited polynuclear gold(I) complexes in the context of classic radical reactions in organic synthesis was important for their validation as useful photocatalysts. First, the Ueno-Stork cyclization of nonactivated bromoalkanes was used to demonstrate the powerful reducing capabilities of the excited-state gold(I) complexes. Next, a photo-mediated variant of the Appel reaction was described, where the transformation of an alcohol to a bromoalkane was achieved using carbontetrabromide and N,N-dimethylformamide through the intermediacy of a Vilsmeier-Haack reagent. In combination with the hydrodebromination chemistry developed with photoexcited polynuclear gold(I) complexes, a photo-mediated one-pot formal deoxygenation reaction of alcohols was described; a useful alternative to the organostannane mediated Barton-McCombie deoxygenation reaction. Finally, in the field of medicinal chemistry, the functionalization of heteroarenes is of high interest for the discovery of drug candidates and bioactive molecules. In this respect, one of the most useful reactions for the functionalization of heteroarenes by alkyl radicals is the Minisci reaction using silver salts, carboxylic acids, and persulfates. Detailed are the efforts for the development of a photo-mediated redox-neutral improvement of the Minisci reaction, needing only gold(I) photocatalyst and nonactivated bromoalkane in the presence of heteroarenes. Overall, the work described in this thesis represents the push for mild and efficient alternatives to the relatively harsh conditions and/or toxic reagents and byproducts associated with classic radical chemistry. These studies demonstrate the ability to control highly reactive alkyl radical intermediates with the goal of their broader application in synthetic organic chemistry. The use of photoexcited polynuclear gold(I) complexes as potent reductants compared to ruthenium- and iridium-based polypyridyl complexes is illustrated through the genesis of highly reactive alkyl radicals from nonactivated bromoalkanes.

Porous materials have exhibited some remarkable performances in wide range of applications such as in the field of catalysis, gas adsorption, water treatment, bio- imaging, drugs delivery and energy applications. This is due to the pore characteristic of these materials. In fact, their properties depend mainly on the pore size, pore morphology and pore size distribution. The knowledge of understanding the effect of chemical nature of porous materials on the heterogeneous catalysis has significantly increased since last decades resulting in the increase in the development of innovative porous nano-hybrid materials. Scientists have integrated inorganic and organic materials to generate new structures with unique properties. A significant enhancement in their properties have been observed compared to their single components. This research work focuses on the design and tailoring of innovative hybrid materials with intrinsic porosity based on well studied single components for catalysis and energy applications. The first example is represented by the impregnation technique of gold nanoclusters (Au NCs) inside the pores of mesoporous silica nanoparticles (MSNs). The performance of Au NCs/ MSN as catalyst was evaluated by the epoxidation reaction of styrene. It shows a remarkable catalytic activity, high selectivity towards styrene epoxide (74%) and high conversion of styrene (88%). We have also investigated the self-assembly of polyoxomolybdates (P2Mo5O23) and cyclodextrins (CDs) as molecular building blocks (MBBs) through the bridging effect of counter cations (Na+, K+, and Cs+). This assembly has resulted in the formation of seven different crystals to give seven crystal structures of POM-CD MOFs. These novel porous hybrid frameworks with intrinsic porosity and tunable porosity have been well studied and characterized using different techniques. Interestingly, one of these structures (K-PMo-γ-CD) was obtained in good yield (70 % based on γ-CD), and was therefore selected to further study the catalytic performance of this type of the hybrid organic-inorganic structures (POM-CD MOFs). The ketalization process of cyclohexanone with glycol using K-PMo-γ-CD as catalysts, have been chosed as module reaction for this study. Our results showed that the material give the best catalytic performance, which reached its maximum conversion of 99.94 %, at 100oC. Finally, the scope of our research have been extended by combining another porous macrocycle, a trianglamine (TA), with the metal cluster complex system (polyoxometalate). This hybrid framework (POM-TA) have been well designed and synthesized based on molecular recognition. A detailed characterization shows that the POM-TA material has high surface area that suggests that it can be suitable as catalyst for some industrial processes. Our research on such organic-inorganic hybrid frameworks represents a promising enrichment in the field of heterogeneous catalysis. This is largely due to the possibility of combining different molecular building blocks to form a hybrid framework with improved properties such as intrinsic porosity, large surface area, and tunable structural properties.

Heteropolyacids (HPAs), such as phosphotungstic acid (PTA) and phosphomolybdic acid (PMA), with the Keggin structure are well known as solid superacids with estimated pKa of -13. High acidity of HPAs enabled their use as highly active homogeneous catalysts. However, homogeneous catalysis has many drawbacks, e.g. difficult and expensive separation of the used catalyst from the reaction mixture and its recycling. Application of pure HPAs in heterogeneous catalysis is limited by their low surface area and solubility in polar solvents. For increasing their surface area, HPAs should be immobilized on solid support. The objective of this work is the development of an active and stable HPA-containing catalyst for synthesis of long chain alkylbenzenes, which are essential precursors in the manufacture of surfactants. To prevent leachability of HPA from the support, it was covalently bonded into the silica matrix via Si‑O‑W bridges. The catalysts were obtained by co-condensation of tetraethoxysilane (TEOS) with PTA using sol-gel method in the presence of various surfactants as pore-forming agents. The synthesis was conducted by simultaneous addition of 20% HCl and ethanol solution of a mixture of TEOS and PTA to a solution of a surfactant. The reaction mixture was refluxed for 24 h. The obtained product was filtered, washed, air-dried, and calcined for total removal of a surfactant from pores. Use of Pluronic P123 as a non-ionic pore-forming agent produced the most acidic material. The synthesized mesoporous materials were tested as heterogeneous catalysts in liquid-phase alkylation of mesitylene by long-chain alkenes. They demonstrated higher activity than well-known zeolite HY. The analysis of catalyst recovered after the alkylation indicated no PTA leaching from silica matrix. Obtained superacidic mesoporous materials can potentially replace hazardous liquid Lewis acids currently used for long-chain alkylbenzene synthesis in petrochemical industry.

Thesis advisor: Jeffery A. Byers / Thesis advisor: Chia-Kuang Tsung / Homogeneous catalysts are advantageous in selective catalysis due to the well-defined active site at the molecular level. The poor recyclability, bimolecular aggregation, and undesired poison resistance of homogeneous catalysts hinder further industrial application despite the controlled reaction pathway due to the homogeneous environment. On the other hand, heterogeneous catalysts are preferred in industry due to their high recyclability and high activity. Yet, poor selectivity due to undefined active sites is a drawback. The construction of a host-guest system where a molecular level catalyst is incorporated into the Metal-Organic Framework (MOF) provides a promising solution to bridge those two fields. This composite maintains the advantages of homogeneous and heterogeneous catalysts and overcomes the disadvantages. However, finding an incorporation method that is versatile with minimum synthetic modification of the host and guest remains one of the challenges. In the first part of this dissertation, a new concept called “aperture-opening encapsulation’’ is introduced for incorporating large and diverse guest molecules into MOFs without changing the identity of either the guest or MOF. The approach capitalizes on the existence of linker exchange reactions, which, as our kinetic studies show, proceed via competition between associative and dissociative exchange mechanisms. The second part describes how this method is applied to incorporate a molecular catalyst into the cavity of UiO-66 for the hydrogenation of carbon dioxide to formate, which is a useful application for energy related industry. The developed hybrid composite showed the ability to be recycled, showed no evidence of bimolecular catalyst decomposition, and was less prone to catalyst poisoning. These results demonstrate for the first time how the aperture-opening process resulting from linker dissociation in MOFs can be utilized as a strategy to synthesize host-guest materials useful for chemical catalysis. After the establishment of the hybrid catalyst, the last part of the dissertation describes our efforts into the investigation of mass transport in catalysis. The understanding of the interaction between the host-guest is beneficial for the development of biological analogs in the future. / Thesis (PhD) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

A description of the nature of the transition state structure for phosphoryl transfer in the cAPK reaction requires a measurement of the primary 180 isotope effect at the serine hydroxyl acceptor. Since it is difficult to obtain primary 180 isotope effect directly, the 15N/1 4N ratio of the a-amine of the C-terminal glycine in the peptide Leu Arg-Lys-Ala-Ser-Leu-Gly (when serine is phosphorylated) was used to represent on the phosphorylation at serine. 15N Glycine, ' 4N-Glycine and 180 serine were synthesized and used to synthesize two peptides, one containing 1 80-serine/' 5 N glycine and second 1 60-serine/1 4N-glycine. Methods were developed for hydrolyzing the peptides and quantitatively isolating glycine. Partitioning results suggest that catalytic rate was slow compare to substrate dissociation. The 180 primary isotope effect will be determined in the near future using the method developed herein.

Bibliography: pages 129-132. / A synthesis techniQue was developed for the preparation of a nickel oxide sil ica alumina catalyst. The propene oligomerisation activity and the selectivity of the catalysts prepared by homogeneous decomposition deposition (HDD) were investigated and compared with nickel oxide silica alumina catalysts prepared by the techniQues of impregnation (IMP) and co-precipitation (SG). Amongst others. the effect of the nickel content. reacti6n temperature and pressure, and water content of the feed, on the activity and selectivity. were investigated. Also investigated were the lifetime of the various catalysts and, in the case of HDD type catalysts. the ability to oligomerise high molecular weight hydrocarbons (Cb). Nickel oxide silica alumina prepared by the HDD method is more active for the propene oligomerisation than catalysts prepared by the IMP and SG methods. The product spectrum in the case of IMP and HDD type catalysts are similar, with a propene dimer (Cb) being the main product. In the case of SG type catalysts. however. a shift to heavier products was observed, i.e., propene dimer (Cb) and trimer (Cq) were formed in eQual Quantities. It is proposed that the increase in activity of HDD type catalysts was due to a large extent of metal dispersion and distribution and a stronger interaction between the metal and the support. It is also proposed that the metal is readily accessible to the reactant molecules. The activity and selectivity of catalysts prepared by the HDD method were independent of the nickel content. This was not the case for IMP and SG type catalysts. both of which showed decreasing activity with increasing nickel content when the nickel content was increased beyond 5 wt%. The lifetimes of the various catalysts were also examined. From the results obtained. over the first 10 h. the lifetime of HOD type catalysts was superior to that of the other catalysts studied. The activity and selectivity of the various catalysts were sensitive to the reaction conditions. Thus moving into the vapour phase. by either increasing the temperature at a fixed pressure or decreasing the pressure at a fixed temperature. was in each case acCompanied by a shift to heavier products and a decrease in activity.

Rapidly expanding research in nanotechnology has led to exciting progress in a versatile array of applications from medical diagnostics to catalysis. This success resulted from the manipulation of the desired properties of nanomaterials by controlling their size, shape, and composition. Among the most thriving areas of research about nanoparticle is the synthesis and doping of the ligand-protected atomically-precise metal nanoclusters. In this thesis, we developed three different novel metal nanoclusters, such as doped Ag29 with five gold (Au) atoms leading to enhance its quantum yield with remarkable stability. We also developed half-doped (alloyed) cluster of Ni6 nanocluster with molybdenum (Mo). This enabled enhanced stability and better catalytic activity. The third metal nanocluster that we synthesized was Au28 nanocluster by using di-thiolate as the ligand stabilizer instead of mono-thiolate. The new metal clusters obtained have been characterized by spectroscopic, electrochemical and crystallographic methods.