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First Part: Syntheses of Diarylamidophosphino Nickel(II) Complexes and reactivity study We have synthesized [Me-NP-iPr]Ni(CH2SiMe3)(L)(L=2,6-lutidine). In order to compare with [Me-NP-iPr]Ni(CH2SiMe3)(L)(L= pyridine, 2,4lutidine, PMe3), benzene C-H activation reaction experiment were carried out and rate constant were determined by kinetic study. We also synthesized [Me-NP-iPr]Ni(Ph)(2,6-lutidine) to prove the benzene C-H activation product by the trimethylsilylmethyl substituted Ni complex. Solution structure of [Me-NP-iPr]Ni(R)(L)(L=2,6-lutidine; R= CH2SiMe3, Ph) and Solid structure of [Me-NP-iPr]Ni(R)(L)(L=2,6-lutidine; R= Cl, Ph) were characterized by NMR spectroscopy and X-Ray diffraction. Second Part: Syntheses of Diarylamidophosphino Zirconium(IV) Complexes and reactivity test Use [iPr-PNP]Zr(=CHSiMe3)(Cl) as starting material to react with PhMgCl yield [iPr-PNP]Zr(=CHSiMe3)(CH2SiMe3). Solution and Solid structure of [iPr-PNP]Zr(=CHSiMe3)(CH2SiMe3) were characterized by NMR spectroscopy and X-Ray diffraction. Experiments for inducing intramolecular £\-H abstruction to afford [iPr-PNP]Zr(¡ÝCHSiMe3)(L)(L= solvent) were unsuccessful. Attempt to oxidize trimethylsilylmethyl substitution with [PhNHMe2]+[B(C6F5)4]- resulting protonated product {[iPr-PNP]Zr(CH2SiMe3)2}+{B(C6F5)4}-, solution and solid structure were also characterized.

Thesis (B.S.) Magna Cum Laude--Butler University, 2009. / Includes bibliographical references (leaves 17-18).

Thesis (M.S.)--University of Florida, 2004. / Title from title page of source document. Document formatted into pages; contains 47 pages. Includes vita. Includes bibliographical references.

Olefin metathesis has had tremendous impact on synthetic approaches to the formation of new carbon-carbon bonds. Heterogeneous metathesis catalysts have been used in industry for decades, to effect redistribution of olefin chain lengths in petrochemicals processing. Only recently, however, has olefin metathesis emerged in pharmaceutical and specialty chemical manufacturing. The nearly 20-year gap between the discovery of easily-handled ruthenium catalysts and industrial implementation in these sectors is a result of many factors. One key contributor is the limited understanding of decomposition mechanisms that limit the reliability of olefin metathesis. Poor catalyst selectivities and yields remain a challenge for industrial uptake of olefin metathesis. Much academic effort focuses on designing methods and new catalysts for catalyst separation and reuse. Exploration of catalyst decomposition pathways has seen much less study in comparison. The limited recognition of decomposition as a problem in academia is undoubtedly due to the tendency to use high catalyst loadings, which mask catalyst decomposition problems. The catalyst loadings commonly reported in academia need to be decreased by a factor of 100–1000 for industrial viability in many processes. This thesis explores the decomposition of metathesis catalysts bearing a phosphine ligand. Such Grubbs-type catalysts, particularly second-generation versions containing an N-heterocyclic carbene ligand, are the most widely used metathesis catalysts in current use. This study follows up on an earlier discovery from the Fogg group, which showed that pyridine and amine donors drastically accelerate decomposition of the Grubbs catalysts. For the first-generation Grubbs catalyst, decomposition of the resting-state methylidene complex RuCl2(PCy3)2(=CH2) Ru-6 was shown to proceed via nucleophilic attack of PCy3 on the Ru=CH2 bond, forming a σ-alkyl complex that was intercepted and characterized crystallographically. Further reaction led to liberation of the methyl phosphonium salt [MePCy3]Cl 2. Under the same conditions, the second-generation methylidene complex Ru-4a decomposes rapidly without any detectable σ-alkyl intermediate. In this thesis, decomposition of the important second-generation catalysts is shown to proceed via the methylidene-abstraction pathway. These studies centered on the methylidene complex RuCl2(NHC)(PCy3)(=CH2), where the NHC ligand is H2IMes (Ru- 4a) or IMes (Ru-4b). The short lifetime of the σ-alkyl complex was tentatively attributed to the ease of activation of a C–H bond on the NHC ligand (specifically, those on the mesityl o-methyl group). This intermediate could not be observed for Ru-4a, but could be observed for the IMes system Ru-4b. This is suggested to reflect the slower rotation of the H2IMes ligand about the Ru–NHC bond, which promotes C–H activation. Also examined is the ability of other Lewis donors to trigger this methylidene abstraction pathway during catalysis. Lewis donors are shown to greatly accelerate decomposition of a wide range of phosphine-stabilized metathesis catalysts. Remarkably, even weak donors such as water, ethers, alcohols, and nitriles (i.e. functionalities that are widespread among contaminants, functional groups, and “green solvents”) are shown to promote this pathway. Phosphine-stabilized catalysts are generally regarded as more robust towards such donor functionalities, and the detrimental impact of such weak donors has gone widely unrecognized. These findings have profound implications for catalyst choice and use. Finally, a deuterium-labelling study was undertaken, in which the mesityl substituents on the NHC ligand were fully deuterated, to confirm that the proton in the phosphonium salt 2 indeed originates in the mesityl methyl group. Of note, the energies of the PCy3 dissociation and C–H activation steps were found to be closely similar. This was unexpected, given prior evidence that PCy3 loss is rate-determining in the Ru-2 precatalysts, and the much stronger Ru–PCy3 bonding known to be present in the methylidene complexes. This finding highlights the need to impede C-H activation for phosphine-stabilized metathesis catalysts. More broadly, it underscores the risks inherent in the use of phosphine-stabilized catalysts, or indeed of catalysts that are stabilized by a donor group that can function as both a Lewis base, and a nucleophile.

Olefin metathesis is increasingly popular for the construction of carbon-carbon double bonds. In the past two decades, ruthenium metathesis catalysts have seen extensive development. Two marvelous early developments were the introduction of N-heterocyclic carbene (NHC) ligands, which greatly improved catalyst activity, and replacement of a nucleophilic stabilizing ligand (the alkylphosphine PCy3) by a chelated benzylidene-ether. A more recent breakthrough is the introduction of cyclic alkyl amino carbene (CAAC) ligands as alternatives to the NHCs. Over the past 5 years, the CAAC catalysts have drawn much attention for their breakthrough productivity in challenging reactions, including ethenolysis and RCM macrocyclization. Nevertheless, important challenges remain. As discussed in the first part of this thesis, these include the synthesis of key ligands (in particular, the styrenyl ether ligands H2C=13CH-C6H4-2-OiPr and H2C=13CH-C6H3-2-OiPr-5-NO2), which represent the source of the chelated benzylidene-ether noted above) and key catalysts (e.g., Hoveyda- and Grela-class catalysts bearing an H2IMes or CAAC carbene ligand). A further challenge lies in understanding the behaviour of the styrenyl ether ligands – for example, how they contribute to catalyst partitioning between active, resting-state, and decomposed species, and the impact of the carbene ligand on that partitioning. An initial objective was synthesis of labelled styrenyl ethers that would enable synthesis of Hoveyda and Grela catalysts with a 13C-label at the alkylidene carbon. While H2C=13CH-C6H4-2-OiPr could be accessed, its nitro analogue could not, probably owing to attack on the NO2 substituent. The remainder of Chapter 2 assessed reported routes to HII/nG and HII-C1/nG-C1, and reports on challenges and reproducibility issues. Difficulties in synthesis of the CAAC catalysts are attributed to the need for in situ-generated CAACs, and catalyst decomposition by the base required for deprotonation (i.e KHMDS or LiHMDS). The second part of this thesis explores the impact of the NHC or CAAC ligands on initiation and “boomerang” recapture of the styrenyl ether ligands for Hoveyda- and Grela-class catalysts. Examination of the kinetics of initiation with bulky t-butyl vinyl ether (tBuVE) revealed a linear dependence of kobs on [tBuVE], and faster reaction by the p-NO2-substituted Grela catalyst. These data suggest an associative or interchange-associative (IA) mechanism. A systematic comparison of initiation rate constants revealed the trend HII > nG-C1 > HII-C1 in chlorinated and aromatic solvents. Recapture of added styrenyl ether ligand was examined in macrocyclization (mRCM). Rate plots indicated inhibition by this ligand, even at the high dilutions required for mRCM, implying that boomerang re-uptake of the styrenyl ether is indeed operative for both Hoveyda- and Grela-class catalysts. However, inhibition was found to be more profound for HII than HII-C1 or nG-C1. That is, the NHC catalysts are much more susceptible to partitioning into the off-cycle (precatalyst) form than are the CAAC catalysts. This higher commitment to the active cycle may be an important contributor to the impressive productivity of the CAAC catalysts. In addition, the slow initiation of these catalysts indicated above may be an asset, rather than a limitation, as it inhibits their susceptibility to bimolecular decomposition.

Olefin metathesis is an exceptionally versatile and general methodology for the catalytic assembly of carbon-carbon bonds. Ruthenium metathesis catalysts have been widely embraced in academia, and are starting to see industrial uptake. However, the challenges of reliability, catalyst productivity, and catalyst cost have limited implementation even in value-added technology areas such as pharmaceutical manufacturing. Key to the broader adoption of metathesis methodologies is improved understanding of catalyst decomposition. Many studies have focused on phenomenological relationships that relate catalyst activity to substrate structure, and on the synthesis of new catalysts that offer improved activity. Until recently, however, relatively little attention was paid to catalyst decomposition. The first part of this thesis explores a largely overlooked decomposition pathway for “second-generation” olefin metathesis catalysts bearing an N-heterocyclic carbenes (NHC) ligand, with a particular focus on identifying the Ru decomposition products. Efforts directed at the deliberate synthesis of these products led to the discovery of a succinct, high-yielding route to the second-generation catalysts. Multiple reports, including a series of detailed mechanistic studies from our group, have documented the negative impact of phosphine ligands in Ru-catalyzed olefin metathesis. Phosphine-free derivatives are now becoming widely adopted, particularly in pharma, as recognition of these limitations has grown. Decomposition of the phosphine-free catalysts, however, was little explored at the outset of this work. The only documented pathway for intrinsic decomposition (i.e. in the absence of an external agent) was -hydride elimination of the metallacyclobutane (MCB) ring as propene. An alternative mechanism, well established for group 3-7 and first-generation ruthenium metathesis catalysts, is bimolecular coupling (BMC) of the four-coordinate methylidene intermediate. However, this pathway was widely viewed as irrelevant to decomposition of second-generation Ru catalysts. This thesis work complements parallel studies from the Fogg group, which set out to examine the relevance and extent of BMC for this important class of catalysts. First, -hydride elimination was quantified, to assess the importance of the accepted pathway. Even at low catalyst concentrations (2 mM Ru), less than 50% decomposition was shown to arise from -hydride elimination. Parallel studies by Gwen Bailey demonstrated ca. 80% BMC for the fast-initiating catalyst RuCl2H2IMes(=CHPh)(py)2 GIII. Second, the ruthenium products of decomposition were isolated and characterized. Importantly, and in contrast to inferences drawn from the serendipitous isolation of crystalline byproducts (which commonly show a cyclometallated NHC ligand), these complexes show an intact H2IMes group. This rules out NHC activation as central to catalyst decomposition, suggesting that catalyst redesign should not focus on NHC cyclometallation as a core problem. Building on historical observations, precautions against bimolecular coupling are proposed to guide catalyst choice, redesign, and experimental setup. The second part of this thesis work focused on the need for more efficient routes to second-generation Ru metathesis catalysts, and indeed a general lack of convenient, well-behaved precursors to RuCl2(H2IMes). This challenge was met by building on early studies in which metathesis catalysts were generated in situ by thermal or photochemical activation of RuCl2(p-cymene)(PCy3) in the presence of diazoesters. Such piano-stool complexes (including the IMes analogue) have also been applied more broadly as catalysts, inorganic drugs, sensors, and supramolecular building blocks. However, RuCl2(p-cymene)(H2IMes), which should in principle offer access to the RuCl2(H2IMes) building block, has been described as too unstable for practical use. The basis of the instability of RuCl2(p-cymene)(H2IMes) toward loss of the p-cymene ring was examined. Key factors included control over reaction stoichiometry (i.e. limiting the proportion of the free NHC), limiting exposure to light, and maintaining low concentrations to inhibit bimolecular displacement of the p-cymene ring. A near-quantitative route to RuCl2(p-cymene)(H2IMes) was achieved using appropriate dilutions and rates of reagent addition, and taking precautions against photodecomposition. This approach was used to develop atom-economical syntheses of the Hoveyda catalyst, RuCl2(H2IMes)(=CHAr) (Ar = 2-isopropoxybenzylidene) and RuCl2(H2IMes)(PPh3)(=CHPh), a fast-initiating analogue of GII. Related p-cymene complexes bearing bulky, inflexible imidazolidene or other donors may likewise be accessible.

Thesis advisor: Amir H. Hoveyda / Chapter 1. Catalytic olefin metathesis has developed into a powerful tool in the arsenal of the synthetic chemist as a quick and reliable method to build complexity in biologically active molecules. One particular subset of this class of reactions, catalytic olefin cross-metathesis, has seen great strides within the last decade. Using recently reported well-defined catalysts, chemists have been able to synthesize olefins in a stereoselective fashion via this reaction in a laboratory setting. While many classes of Z olefins have succumbed to this transformation, one class of olefins that has not been synthesized in a selective manner is that of Z-unsaturated esters, precious motifs found in a myriad of natural products. Traditional preparations of Z-acrylates and Z-dienoates are presented drawing examples from both total syntheses as well as method development reports. Chapter 2. A catalytic olefin cross-metathesis reaction utilizing E-dienoates as substrates is presented. A large variety of functionalized (E,Z)-dienoates are prepared in high yields and high stereoselectivities. This method has many advantages over more common methods of making these motifs, such as a wider substrate scope and the ability to be performed at ambient temperature. / Thesis (MS) — Boston College, 2015. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 267-282). Available also in a digital version from Dissertation Abstracts.

Thesis (Ph. D.)--University of Texas at Austin, 2003. / Vita. Includes bibliographical references. Available also from UMI Company.