Rhodium complexes bearing multidentate nitrogen donor ligands were investigated for their ability to promote alkyne and olefin functionalization reactions. This thesis work is comprised of two projects in which rhodium-heteroatom reactivity is investigated: P-H bond activation reactions and olefin functionalizations via rhodaoxetane intermediates. [Tp*Rh(PPh3)2] [Tp* = hydrotris(3,5-dimethylpyrazolyl)borate] and [Tp*Rh(cod)]2 (cod = cyclooctadiene) were evaluated for their activity in alkyne hydrophosphinylation in comparison to known catalysts for this reaction. [Tp*Rh(PPh3)2]and [Tp*Rh(cod)]2 were both shown to effect hydrophosphinylation of 1-octyne with diphenylphosphine oxide with high regioselectivity but moderate yields in comparison with Wilkinson's catalyst [C1Rh(PPh3)3]. [Tp*Rh(PPh3)2] was further shown to effect hydrophosphinylation of a range of aromatic and aliphatic alkynes with diphenylphosphine oxide, in each case exclusively providing the E-linear vinylphosphineoxide product. 1H and 31P NMR spectroscopy provided evidence that alkyne hydrophosphinylation in the presence of pyrazolylborate rhodium complexes follows an analogous mechanism to that proposed for this reaction catalyzed by [C1Rh(PPh3)3] or[C1Rh(cod)]2. The 2-rhodaoxetane [(TPA)Rhmec2_,-4u, 0-2-oxyethypr BPh4- (TPA = tris[(2-pyridal)methyl]amine) was investigated for its potential as an intermediate in proposed functionalization reactions of olefins. RTPA)Rh111(K2-C,0-2-oxyethyl)]+ BPh4- was prepared by two published methods with limited success. A third method involved the use of nitrous oxide to oxygenate [(12-ethene)(K4-TPA)Rh1]+ to RTPA)Rh1110(-2-C,0-2-oxyethyDr. Only a trace amount of [(TPA)Rhmoc2 -C,0-2-oxyethypr was observed in the 1I-1 NMR spectrum of this reaction mixture. Initial test reactions of [(TPA)Rhilioc2_C,0-2-oxyethypr combined with substrates (aniline, toluenesulfonamide, phenylboronic acid, or benzaldehyde) were inconclusive since the results were obscured by the impurity of the samples. / Science, Faculty of / Chemistry, Department of / Graduate

Over the past 15 years, ruthenium-catalyzed olefin metathesis has emerged as a cornerstone synthetic methodology in academia. Applications in fine-chemicals and pharmaceutical manufacturing, however, are just beginning to come on stream. Industrial uptake has been impeded by economic constraints associated with catalyst costs. These are due both to direct costs (exacerbated by intellectual property issues), and to further pressure exerted by the low turnover numbers attainable, and the need for extensive purification to remove ruthenium residues. From another perspective, however, these difficulties can be seen as arising from our rudimentary understanding of the fundamental organometallic chemistry of the Ru=CHR bond. In particular, we know little about the nature and reaction pathways of the Ru-methylidene unit present in the active species that propagates metathesis, and in the catalyst resting state. We know slightly more about the ruthenacyclobutane species, but still too little to guide us as to their non-metathetical reaction pathways, their contribution to deactivation relative to the methylidene species, and potential work-arounds. This thesis work was aimed at improving our understanding of the reactivity, speciation, and decomposition of key ruthenium intermediates in olefin metathesis. A major focus was the behaviour and deactivation of species formed from the second-generation Grubbs catalyst RuCl2(H2IMes)(PCy3)(=CHPh) (S-GII), which dominates ring-closing metathesis. Also studied were derivatives of the corresponding IMes catalyst A-GIIm, containing an unsaturated Nheterocyclic carbene (NHC) ligand. The methylidene complexes RuCl2(NHC)(PCy3)(=CH2) (GIIm) represent the resting state of the catalyst during ring-closing and cross-metathesis reactions: that is, the majority Ru species present during catalysis. Mechanistic studies of these key intermediates have been restricted, however, by the low yields and purity with which they could be accessed. Initial work therefore focused on designing a clean, high-yield route to the second-generation Grubbs methylidene complexes S-GIIm and A-GIIm. These routes were subsequently expanded to develop access to isotopically-labelled derivatives. Locating a 13C-label at the key alkylidene site, in particular, offers a powerful means of tracking the fate of the methylidene moiety during catalyst deactivation. Access to GIIm enabled detailed studies of the behaviour and decomposition of the Grubbs catalysts. First, the long-standing question of the impact of saturation of the NHC backbone (i.e. IMes vs. H2IMes) was examined. Dramatic differences in the behaviour of the two complexes were traced to profound differences in PCy3 lability arising from the diminished π-acidity of the IMes ligand. Secondly, the vulnerability of GIIm to nucleophiles was examined. This is an important issue from the perspective of decomposition by adventitious nucleophiles in the reaction medium during catalysis, but also reflects on substrate scope. For amine additives, the dominant deactivation pathway was shown to typically involve attack on the resting-state methylidene complex, not the metallacyclobutane, which has often been regarded as the most vulnerable intermediate. In addition, the sigma-alkyl intermediate formed by nucleophilic attack of displaced phosphine at the methylidene carbon was trapped by moving to the first-generation complex, and using a nitrogen donor (pyridine) that cannot promote decomposition via N–H activation pathways. Interception of this long-suspected species led to the proposal of “donorinduced” deactivation as a general decomposition pathway for Grubbs-class catalysts. Finally, the capacity of phosphine-free catalysts to overcome the shortcomings of the secondgeneration Grubbs catalysts was demonstrated, in a case study involving application of crossmetathesis (CM) to the synthesis of a high-value antioxidant. An efficient CM methodology was developed for the reaction of renewable essential-oil phenylpropenoids with vinyl acrylates. This work illustrates a new paradigm in sustainable metathesis. Rather than degrading unsaturated feedstocks via metathesis (a process that can be termed “metathe[LY]sis”), it demonstrates how metathesis with directly-functionalized olefins can be used to augment structure and function. From the perspective of organometallic chemistry and catalyst design, key comparisons built into this thesis are the effect of the NHC ligand (IMes vs. H2IMes) and its trans ancillary ligand on the efficient entry into catalysis; the susceptibility to nucleophilic attack of the alkylidene ligand (benzylidene vs. methylidene) vs. the metallacyclobutane; and the effect of replacing a phosphine ancillary ligand with a non-nucleophilic donor. From a practical standpoint, Chapter 2 brings new life to metathesis with the high-yield synthesis of the resting state species, Chapters 3 and 4 examine the deactivation, or death, of the methylidene complexes, and Chapter 5 establishes a new paradigm for olefin metathesis within the context of sustainable synthesis.

Olefin metathesis is the most powerful, versatile reaction in current use for the formation of new carbon-carbon bonds. While metathesis has been known for over 60 years, it has only recently been implemented into pharmaceutical and specialty chemical manufacturing. The slow uptake of olefin metathesis can be attributed in part to low catalyst productivity, a consequence of short catalyst lifetime. Improving catalyst activity is critical for the advancement of metathesis. This improvement can be achieved through greater understanding of the catalysts and their limitations. The ability to perform metathesis in aqueous media is desirable, but as yet largely unrealized, for the modification of water-soluble, biologically-relevant substrates. At present, high catalyst loadings are necessary even for less demanding metathesis reactions in water. The limited mutual solubility of the catalyst and substrate in water are one limitation. Examined in this thesis are more fundamental challenges associated with catalyst deactivation by water. The impact of water on catalyst productivity was assessed for both the second-generation Grubbs catalyst GII, and the phosphine-free Hoveyda catalyst HII, in ring-closing and cross-metathesis reactions. Water was shown to have a negative impact on metathesis productivity, owing to catalyst decomposition. The decomposition pathway was catalyst-dependent: GII was found to decompose through a pathway in which water accelerated abstraction of the methylidene ligand by dissociated phosphine. For HII, water was found to decompose the metallacyclobutane intermediate. A β-hydride transfer mechanism was proposed, to account for the organic decomposition products observed. Chapter 4 focuses on problems encountered during the synthesis of ruthenium catalysts, and presents improved methods. An updated method was developed for the synthesis of phenyldiazomethane, the principal source of the alkylidene ligand required in synthesis of GI. Challenges in use of the phosphine-scavenging resin Amberlyst-15 resin are discussed. Improving synthetic routes to the important first- and second-generation Grubbs catalysts will aid in expansion of olefin metathesis methodologies, particularly in the industrial context, in which batch-to-batch reproducibility is paramount.

Olefin metathesis is arguably the most versatile catalytic route yet developed for the assembly of carbon-carbon bonds. Metathesis methodologies are attractive from both synthetic and ecological standpoints, because they employ unactivated double bonds. This reduces the total number of synthetic steps, and the associated generation of chemical wastes. The drive to deploy olefin metathesis in highly demanding contexts, including pharmaceutical manufacturing and chemical biology, puts severe pressure on catalyst lifetime and productivity. Understanding the relevant decomposition pathways is critical to achieve essential performance goals, and to enable informed catalyst redesign. This thesis work expands on significant prior advances that identified and quantified critical decomposition pathways for ruthenium catalysts stabilized by N-heterocyclic carbene (NHC) ligands. Because pristine catalyst materials are essential for mechanistic study, it focuses first on methods aimed at improving efficiency and purity in catalyst synthesis. Merrifield iodide resins were shown to function as efficient, selective phosphine scavengers in the production of clean second-generation catalysts from PCy3- stabilized precursors. The thesis then turns to mechanistic examination of decomposition pathways that underlie success and failure for leading NHC catalysts, for comparison with a new family of catalysts stabilized by cyclic (alkyl)(amino) carbene (CAAC) ligands. These represent the first in-depth mechanistic studies of the CAAC catalysts, which have attracted much attention for their breakthrough productivities in challenging metathesis reactions. The remarkable productivity of the CAAC catalysts is shown to originate in their resistance to decomposition of the key metallacyclobutane intermediate via b-elimination, and (to a lesser extent) in their resistance to attack by nucleophiles and Bronsted bases. Importantly, however, they are more susceptible to bimolecular decomposition. The latter behaviour, as well as their resistance to b-elimination, is traced to the strong trans influence of the CAACs relative to NHC ligands. This insight significantly advances our understanding of the fundamental properties governing both productivity and decomposition. Finally, two new catalysts are developed, building on the principle that nucleophilic stabilizing ligands should be avoided in the precatalysts. In the first of these complexes, an o-dianiline ligand is employed to stabilize the precatalyst. This flexible, H-bonding chelate serves the further purpose of accelerating macrocyclization of flexible dienes that bear polar functionalities. As its H-bonding capacity also increases its sensitivity to trace water, however, an alternative catalyst architecture was pursued. The latter consists of a dimer bearing bulky Ru-indenylidene centers, in which a dative bond from a bridging chloride affords the fifth ligand essential to stabilize the precatalyst.

The development of new strategies to access pyridinium salts are highly sought out due to their advantageous structures, which have diverse applications across materials science, biological processes, and organic synthesis. As synthetic intermediates, these scaffolds can be used as precursors to valuable piperidine derivatives and have recently emerged as important cross coupling handles for metal-catalyzed processes. Unfortunately, current methods to access pyridinium salts are limited; they require harsh conditions, rely on the presence of an amine functional handle, and are not amenable to diverse structural variation. In Chapter 1, a summary of various syntheses and the reactivity of pyridinium salts is provided. This dissertation provides new strategies to access pyridinium salts. The first method is via aminolactonization of alkenoic acids, resulting in 1° pyridinium salts (Chapter 2). The second method is a regioselective synthesis of 3-aminopiperidine salts via diamination of olefins (Chapter 3). Both methods are promoted by nitrogen-ligated hypervalent iodine reagents (N-HVIs). These novel class of reagents serve as “heterocyclic group transfer reagents,” incorporating diverse pyridinium salts under mild conditions and in excellent yields. Heterocyclic Group Transfer reactions have resulted in new classes of pyridinium salts that can be further functionalized via simple known methods to access diverse piperidine motifs, providing an innovative approach to substitution patterns that were previously challenging to synthesize. These strategies have also enabled pyridinium salts to be viewed as a synthetic platform for diversity-oriented amine synthesis. Chapter 4 will elaborate on the synthesis of different classes of 3-aminopiperidine motifs using hypervalent iodine reagents; these motifs have been previously synthesized using transition metal catalysis. / Chemistry

No description available.

Thesis advisor: Marc L. Snapper / Tandem Reactions have proven themselves to be useful reactions for the synthesis of highly complex materials. Ruthenium alkylidenes are shown to be useful precursors for the development of new tandem processes. First, a new tandem metathesis/hetero-Pauson-Khand process is developed using Grubbs' second generation catalyst. Next, various metatheis/olefin isomerization processes are explored. / Thesis (PhD) — Boston College, 2009. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

This dissertation delves into the catalytic activity of multiple metal-containing complexes with an emphasis on the activation of C–H bonds in small molecules and olefin oligomerization. The research contained in these works employs computational methodologies to better understand the thermodynamics and kinetics of the reactions. Computations can be used to quickly identify novel models and find ideal substitutions for improved catalyst design. Within this dissertation, multiple molecules of divalent and trivalent main group element-containing complexes as well as Group 13 dimetallene complexes were investigated with density functional theory (DFT) to identify their ability to activate C–H of hydrocarbons, including methane, by quantifying their thermodynamics and kinetics of reaction. With several substitutions to the base complex, improved catalysts were designed to decrease the energy barriers of the activations. Multiconfiguration self-consistent field methods were also employed to characterize the biradical character of these Group 13 compounds. Olefin oligomerization by zirconium boratabenzenes with various ancillary pendant groups was also investigated via DFT to identify the most ideal variations as well as the most likely reaction pathway.

Aluminum- and gallium-bridged ansa-zirconocene compounds (Pytsi)Al[1]ZCP (31a) and (Pytsi)Ga[1]ZCP (31b) containing a bulky trisyl-based ligand with a pyridyl donor group [Pytsi = -C(SiMe3)2SiMe2(2-C5H4N)] were synthesized in 31% and 40% yield, respectively, by the reaction of (Pytsi)ECp2 [E = Al (29a), Ga (29b)] with Zr(NMe2)4 followed by reaction with Me3SiCl. Compounds 29a and 29b were prepared by the reaction of (Pytsi)ECl2 [E = Al (28a), E = Ga (28b)] with two equivalents of NaCp. The molecular structures of 29a and 29b were elucidated in solution by 1H and 13C NMR spectroscopy. Species 31a was characterized by multinuclear NMR spectroscopy while 31b was characterized by CHN elemental analysis, 1H and 13C NMR spectroscopy and mass spectrometry. Both species are the only known examples of aluminum- and gallium-bridged ansa-zirconocenes. Compound 31b in combination with MAO was applied and shown to be highly active for ethylene polymerization at room temperature. The activity of 31b was compared to that obtained for Cp2ZrCl2 using a glass reactor system and was found to be comparable. The influence of precatalyst concentration and ethylene pressure on activity of 31b was studied.

Olefin/Paraffin separation, traditionally carried out by cryogenic distillation, is difficult to achieve due to the similar size and volatility of the components. Recently, many studies have explored membrane separation methods that utilize a metal ion to facilitate preferential olefin transport across the membrane. However, much of this work focuses on smaller molecules, C2-C3, which are gaseous at room temperature, while little work has been done studying separation of larger molecules, C5 and greater, which are generally liquid at room temperature. The processes developed to separate small molecules are not necessarily directly applicable to separate larger molecules. A polymer electrolyte membrane consisting of an active layer of polyethylene oxide (PEO) and silver tetrafluoroborate (AgBF4) has shown high selectivity for separating gaseous olefin/paraffin mixtures. The current project investigates the feasibility of applying this membrane to the separation of pentene and pentane (liquid C5 olefin and paraffin). Process variables investigated are the: pure component permeability ratio, equilibrium sorption uptakes, pure component diffusivities, and stable membrane lifetime. Permeation tests on individual species (n-pentane and 1-pentene) were performed in two operating modes with membranes of varying silver concentrations: direct liquid contact to the membrane, and vapour contact to the membrane. The vapour contact mode showed improved membrane stability in comparison to the liquid contact mode. The olefin/paraffin permeability ratio increases with increasing silver content in the membrane, however, the membrane selectivity is much lower than that achieved with smaller olefin/paraffin pairs. Selective chemical interactions between pentene and the membrane were observed, as the pentene sorption uptake is higher than that of pentane. In addition, a residual fraction is observed – a fraction of the pentene does not desorb from the membrane at ambient conditions – indicating a permanent or semi-permanent interaction. Desorption of pentane is determined to follow a Fickian diffusion model, while desorption of pentene appears to be governed by pseudo-second order kinetics.