Des complexes de Cyclodextrine (CD)-NHC-Métaux (NHC= Carbènes N-Hétérocycliques), comprenant des métaux tel que AgI, CuI et AuI ont été synthétisés. Une étude structurale a mis en évidence la position intra-cavitaire du métal, induisant des interactions C-H…M, C-H…X et π…X. L’influence du type de cavité (α-, β-, γ-CD) et du type de dérivés NHC (Imidazole, benzimidazole, triazole) a été étudiée. Les interactions diminuent avec l’augmentation de la taille de la cavité et en parallèle, celles-ci ont été amplifiées avec des dérivés NHC possédant un effet donneur plus fort. Les complexes de cuivre correspondants montrent une bonne réactivité pour la réaction d’hydroboration des alcynes. Il a de plus été observé que la sélectivité est dépendante de la taille de la cavité. En effet, alors que le complexe α-CD-Cu donne le produit linéaire, le complexe β-CD-Cu oriente vers la formation de l’isomère branché. Les espèces CD-Cu potentiellement impliquées dans le cycle catalytique ont été étudiées. Deux mécanismes différents sont ainsi proposés. Dans la réaction catalysée par le complexe α-CD-Cu, le processus catalytique a lieu en dehors de la cavité; tandis que lorsque la cavité est plus grande (β-CD) la catalyse a lieu à l’intérieur de la celle-ci. Par ailleurs, les complexes ont également montré une différente énantiosélectivité et régiosélectivité dans une réaction de cycloisomerization catalysée par des comlexes dor, en fonction de la taille de la cavité de ces catalyseurs. Les résultats catalytiques ont prouvé que les complexes CD-NHC-Métaux fonctionnent comme des catalyseurs pour lesquels la taille de la cavité influe sur la séléctivité. / Cyclodextrin (CD)-NHC-Metal complexes (NHC=N-Heterocyclic Carbene), including the AgI, CuI and AuI complexes were synthesized. A structural study showed that the metal was inside the cavity, and induced by C-H…M, C-H…X and π…X interactions. Variations on α-, β-, γ-CD cavities and NHC derivatives (midazole, benzimidazole, triazole) were studied. When the size of the cavity increased, these interactions decreased. Furthermore, stronger σ-donating effects lead to stronger interactions. CD-Cu complexes showed good activity in catalytic hydroboration of alkynes. The selectivity is depending on the size of the cavity of the catalyst. α-CD copper complex gives linear hydroboration products, while β-CD copper complex yields the branched isomers. The CD-Cu species potentially involved in the catalytic cycle were studied, two different mechanisms were thus proposed. In the α-CD-Cu complex catalyzed reactions, the catalytic process takes place outside the cavity; while a bigger cavity β-CD permits the catalysis to take place inside the cavity. Furthermore, the gold complexes also show different enantioselectivity and regioselectivity in cycloisomerization using different cavity-based catalysts. Catalytic results evidenced the selectivity of a catalytic reaction is dependent on the cavity of the CD-NHC-metal complexes.

Cette thèse porte sur l’étude de nouveaux carbènes N-hétérocycliques dont les atomes d'azote sont substitués par des groupes étendus alkylfluorényle (AF). Les caractéristiques principales de ces coordinats sont leur fort encombrement stérique, la modularité de ce dernier, et la proximité créée dans les complexes correspondants entre les groupes AF et le métal coordiné.La première partie de ce travail décrit la synthèse et la caractérisation d'un ensemble de sels d’azolium, précurseurs de cette nouvelle famille de NHCs. Ces composés ont d'abord été utilisés pour la préparation de complexes de palladium de type "Pd-PEPPSI-NHC", complexes qui se sont avérés très efficaces en couplage de Suzuki-Miyaura entre acides arylboroniques et chlorures d’aryle para-substitués. Des études structurales et RMN ont montré que dans leur complexes, les NHC formés agissent comme des pinces bimodales, c'est-à-dire combinant une interaction covalente (la liaison M-Carbène) et deux interactions non-covalentes impliquant les groupes AF. Dans certains complexes linéaires de l’or(I) et du cuivre (I), ces interactions faibles entre le métal et des liaisons C-H alentours ont permis la coordination non-optimale du centre métallique qui, à l’état solide, se retrouve hors de l’axe formé par le doublet non liant du carbène. Enfin, un complexe de type CuCl(NHC) dont l’encombrement stérique est variable a été préparé. Il s’est avéré être un excellent catalyseur d’hydrosilylation d’aldéhydes et de cétones. A ce jour, il possède l’une des plus grandes activité et longévité (TONs jusqu’à 1000) pour ce type de complexe / This thesis deals with a series of N-heterocyclic carbene ligands (NHCs) in which the N atoms bear expanded alkylfluorenyl (AF) substituents. Special focus has been put on the steric properties of these new ligands, as well as their influence on catalytic reactions involving Pd and Cu centres.The first part of this work describes the synthesis of a series of AF-substituted azolium salts suitable for the preparation of palladium PEPPSI-NHC complexes. These turned out to be very active in Suzuki-Miyaura cross-coupling reactions between para-substituted aryl chlorides and arylboronic acids. Structural and NMR studies revealed that in all the complexes, the NHC ligand displays a "bimodal pincer" type behaviour, that is functions as a tridentate ligand bound to the metal through both covalent and non covalent bonds, the former involving the carbenic C atom, the latter CH atoms of the wingtips.In the second part of the study, a series of linear [AuCl(NHC)] and [CuCl(NHC)] complexes were prepared. In some of them were observed weak CH•••M interactions involving the alkyl chains fixing the metal centre in a position below the NHC ring plane. This leads to an unusual coordination of the ligand able to freeze out the movement of the metal centre during its natural oscillation about the M-carbene axis.In the last part of this thesis, one of the [CuCl(NHC)] complexes synthesised was shown to be highly efficient in the catalytic hydrosilylation of functionalised/sterically crowded aldehydes and ketones (TONs up to 1000). Its high stability was attributed to the variable encumbrance of the ligand.

Les nanomatériaux ont beaucoup captivé l'attention pour leur propriétés uniques, fortement associées à leurs dimensions nanoscopiques. En particulier, les nanoparticules (NP) à base de métaux nobles (Au, Ag) présentent des propriétés mécaniques, électroniques, optiques et magnétiques particulières intéressantes pour le développement d'applications dans de nombreux domaines à fort impact sociétal. En raison de leur stabilité élevée par rapport aux autres nano- particules métalliques, les nanoparticules d'or ont été abondamment explorées pour les nanotechnologies. Ces dernières décennies, les NHC ont émergé en tant que classe essentielle de ligands neutres en chimie organométallique. Les NHC sont caractérisés par leur flexibilité synthétique élevée, leur géométrie spécifique, et une liaison métal–Ccarbène très forte dans les complexes métalliques. Toutes ces propriétés ont été largement étudiées et exploitées pour les applications en catalyse homogène et pour le développement de complexes biologiquement actifs. Par comparaison, l'utilisation des NHC dans les matériaux reste largement peu explorée. Dans ce travail, le potentiel de ligands NHC dans le domaine des nanomatériaux, comme des agents de revêtement pour le produit nanocristaux de synthèse de l'or (et l'argent), la produit de stabilisation et de l'auto-assemblage dans supracrystals ont été explorés. Tout d'abord, des complexes d'argent et d'or-NHC qui sont bien définies avec différents ligands qui sont connus comme le NHC, sont étudiés pour leur pertinence afin de générer des astable nanocristaux (NCs) dans des conditions réductrices avec un bon contrôle de la taille des nanocristaux. Nous démontrons que le Au et le Ag NCs peuvent tous être formés par la réduction des complexes métal-NHC avec les amine-boranes. L'efficacité du procédé, la taille moyenne et la taille de la répartition des nanocristaux dépendent fortement de la structure du ligand NHC. Cependant, nous démontrons dans cette partie que les différentes voies sont impliqués à générer des nanocristaux par Au ou Ag précurseurs, comme une spécifique réaction observée entre Ag-NHC et thiols conduisant à la formation de thiolates argent alors que le Au-NHC correspondant reste inchangé... / Nanomaterials have received extraordinary attention owing to their unique properties, strongly associated to their nanoscale dimensions. In particular, noble metal (Au, Ag) nanoparticles (NPs) exhibit particular mechanical, electronic, optical and magnetic properties and present a high potential for developing applications in many domains with important societal impacts. Due to their higher stability by comparison with other metal-based nanoparticles, Au NPs have been extensively investigated for research in nanotechnology. In the last decades, N-Heterocyclic carbenes (NHCs) have emerged as an essential class of neutral ligands in organometallic chemistry. NHCs are characterized by their high synthetic flexibility, their specific geometry, and a very strong metalCcarbene bond in metal complexes. All these properties have been widely studied and exploited for applications in homogeneous catalysis and for the development of biologically active complexes. By comparison, the use of NHCs in nanomaterials remains largely unexplored. In this work, the potential of NHC ligands in the field of nanomaterials, as coating agents for gold nanocrystals synthesis, stabilization and self-assembly into supracrystals has been explored. First, well-defined silver and gold–NHC complexes with different well-known NHC ligands are investigated for their relevance to generate stable nanocrystals (NCs) under reductive conditions with a good control of nanocrystals size. We demonstrate that both Au and Ag NCs can be formed by reduction of metal-NHC complexes with amine-boranes. The efficiency of the process and the average size and size distribution of the nanocrystals markedly depends on the structure of the NHC ligand. However, we demonstrate in this part that different pathways are involved to generate nanocrystals from Au or Ag precursors, as a specific reaction is observed between Ag-NHCs and thiols leading to the formation of silver thiolates whereas the corresponding Au-NHCs remain unchanged...

Chapter one is an introduction, outlining the structure and bonding of N-heterocyclic carbenes (NHCs). It then goes on to give examples of f -metal NHC complexes and describes any reactivity or catalytic activity. Chapter two describes the synthesis of the transition metal NHC complexes [Fe (LMes)2] 3 and [Co(LMes)2] 4 (LMes = OCMe2 CH2(1-C{NCH2CH2NMes})). The heterobimetallic complexes [(LMes)Fe(μ-LMes)U(μ-{N(SiMe3)Si(Me)2CH2})(N(Si Me3)2)2] 5 and [(LMes)Co(μ-LMes)U(μ-{N(SiMe3)Si(Me)2CH2})(N(SiMe3)2)2] 6 were prepared from the reaction between [({Me3Si}2N)2U(NSiMe3SiMe2CH2)] and 3 or 4, respectively. Complex 5 was also synthesised by the reaction between 3 and [U(N{SiMe3}2)2]. The diamagnetic analogue [(LMes)Zn(μ-LMes)Th(μ-{N(SiMe3)Si (Me)2CH2})(N(SiMe3)2)2] 9 was prepared from the reaction between [Zn(LMes)2] and [({SiMe3}2N)2Th(NSiMe3SiMe2CH2)]. The reactivity of 5 is discussed. When 5 was reacted with 2,6-dimethylphenyl isocyanide, [({SiMe3}2N)2U{N(SiMe3)Si(Me2)C(CH2)N(2,6−Me−C6H3)}] 8 was isolated. The reaction with CO resulted in the formation of [({Me3Si}2N)2U{N(SiMe3) Si(Me2)C(CH2)CO}]. 5 showed no reactivity with azides, boranes or m-chloroperbenzoic acid and decomposed when exposed to H2, CO2 or KC8. The reaction between 6 and 2,6-di-tert-butylphenol formed the previously reported monometallic complex [({SiMe3}2N)2U(OC6H3tBu2)]. The serendipitous synthesis of the iron ate complex [Na(Fe{LMes}2)2]+ [Fe(ArO)3]– 10 (Ar = 2,6-tBu-C6H3) is also described. Chapter three describes the synthesis of the aryloxide complexes [HC(3-tBu-5-Me- C6H2OH)(3-tBu-5-Me-C6H2O)μ-(3-tBu-5-Me-C6H2O)Co(THF)]2 11 and [HC(3- tBu-5-Me-C6H2OH)(3-tBu-5-Me-C6H2O)μ-(3-tBu-5-Me-C6H2O)Zn(THF)n] 13. Treatment of 11 with pyridine N-oxide resulted in the formation of the pyridine-Noxide adduct [HC(3-tBu-5-Me-C6H2OH)(3-tBu-5-Me-C6H2O)μ-(3-tBu-5-Me-C6H2 O)Co(C5H5NO)]2 12. When 11 was treated with [({Me3Si}2N)2U(NSiMe3SiMe2C H2)], no reaction occured at room temperature but at 80◦C decomposition occured. When 11 was treated with [(NH4)2Ce(NO3)6] the protonated proligand HC(3-tBu- 5-Me-C6H2OH)3 reformed. The reactivity of 11 with [({Me3Si}2N)Ce(LiPr)2] is also discussed. Chapter three also discusses the preparation of the heterobimetallic complex [HC(3- tBu-5-Me-C6H2O)2-μ-(3-tBu-5-Me-C6H2O)KCo]2 14 and the salt-elimination chemistry of the complex. The preparation of [HC(3-tBu-5-Me-C6H2O)2-μ-(3-tBu-5- Me-C6H2O)KZn]2 15 is also outlined. Chapter four discusses the reactivity of [Ce(LiPr)3] (Li Pr =OCMe2CH2(1-C{NCHC HNiPr})) in C-H and N-H activation and as a catalyst for organic reactions. [Ce(LiPr)3] displayed no C-H activation chemistry with RC−−−CH (R = SiMe3, Ph, tBu), diphenyl acetone, indene or fluorene. [Ce(LiPr)3] also showed no N-H activation chemistry with pyrrole or indole, nor did it react with the lignin model compound PhOCH2Ph. When treated with an excess of benzyl chloride, [Ce(LiPr)3] underwent ligand decomposition to form the acylazolium chloride [(C6H5C(O))OCMe2CH2(1-C(C6H5C (O)){NCHCHNiPr})]Cl 18 and CeCl3. When [Ce(LiPr)3] was added to a mixture of benzaldehyde and benzyl chloride, as a coupling catalyst, the complex decomposed. [Ce(LiPr)4] was tested as a catalyst from the benzoin condensation and for the coupling of benzalehyde and benzyl chloride, however, it resulted in the decomposition of [Ce(LiPr)4]. Chapter four also outlines the catalytic activity of 3. The complex showed no reactivity as a hydrogenation catalyst towards alkenes, aldehydes or ketones but did display reactivity as a hydroboration catalyst for alkenes, aldehydes or ketones. Chapter five presents the conclusions for chapters two to four. The final chapter contains the experimental details from the previous chapters.

Syntéza polylaktidu (PLA) polymerací za otevření kruhu cyklického monomeru (ROP) může být uskutečněna různými způsoby. Literatura uvádí více než 100 katalytických systémů, jejichž pomocí lze polylaktid a jiné biodegradabilní alifatické polyestery získat. Například organokovové katalyzátory na bázi Sn, Zn, Al atd. se po splnění své polymerační funkce stávají kontaminanty a pro humánní implantáty je použití takového materiálu diskutabilní. V současné době jsou v centru výzkumné pozornosti nové N-heterocyklické karbenové katalyzátory. Tyto „metal-free“ katalytické struktury jsou schopné reprodukovatelně řídit syntézu polymerů předem definované molekulové hmotnosti s definovanými koncovými skupinami a nízkou polydisperzitou, která je charakteristická pro živý průběh polymerace. Nabízí se možnost syntézy blokových kopolymerů a různorodých makromolekulárních architektur. Předložená diplomová práce se zabývá studiem polymerace cyklického monomeru D,L-laktidu katalyzované N-heterocyklickým karbenem. Polymerace byly vedeny v přítomnosti benzylalkoholu jako iniciátoru v roztoku THF. Byl sledován vliv složení reakčního systému monomer – iniciátor – katalyzátor. Dále byly připraveny polymery opticky čistého L-laktidu s makroiniciátory PEG s Mn = 1000 a 2000 g/mol. Střední číselná molekulová hmotnost (Mn) a polydisperzita (PDI) byly stanoveny pomocí GPC. Definovatelnost koncových skupin vybraných polymerů byla prokázána pomocí 1H NMR.

<div>Carbenes are reactive organic intermediates comprised of a neutral, divalent carbon atom. The reactivity of carbenes is often orthogonal to polar functional groups (nucleophiles and electrophiles), making them valuable intermediates for organic synthesis. For example, carbenes can engage in cheletropic reactions with olefins to form cyclopropane rings or undergo insertions into weak element-hydrogen bonds. The most established strategy for accessing carbene intermediates is through a redox-neutral decomposition of diazoalkanes to form a transient M=CR₂ species. Over the course of nearly a half-century of development, many instrumental synthetic methods have emerged that operate on this basis. Despite the combined utility of these methods, the scope of catalytic carbene transfer reactions remains largely constrained by the inherent instability of the starting materials. Diazoalkanes often require electron-withdrawing groups to provide stability through resonance effects.</div><div>Contrary to redox-neutral methods, reductive carbene transfer reactions utilize non-stabilized 1,1-dihaloalkanes as carbene precursors. The Simmons-Smith cyclopropanation reaction represents the most documented example of this class, and remains today as the most practical method for parent methylene (:CH₂) transfer. Nevertheless, reductive carbene transfer processes have proven to be remarkably resistant to catalysis. Our group is interested in developing first-row transition metal catalysts which can initiate an oxidative addition into 1,1-dihaloalkanes, followed by a two-electron reduction with an outer-sphere reductant to provide access to a M=CR₂ intermediate for carbene transfer.</div><div>The application of this mechanistic hypothesis toward reductive methylene transfer using CH₂Cl₂ as the carbene source and a Ni catalyst is outlined in chapter one. The discovery of an unexpected cyclooligomerization of methylene carbenes is discussed. Mechanistic studies are presented, which are consistent with a pathway in which carbenes are iteratively inserted into an expanding metallacycle. In chapter two, the corresponding activation of 1,1-dichloroalkenes for vinylidene transfer in [5+1]-cycloadditions with vinylcyclopropanes is outlined. Finally, in the third and final chapter, organic reactions catalyzed by complexes which feature metal-metal bonds are reviewed.</div>

The ability of gold(I) to activate many types of unsaturated bonds toward nucleophilic attack was not widely recognized until the early 2000s. One major challenge in gold catalysis is the control over regioselectivity when there are two or more possible products as a result of complicated mechanistic pathways. It is well know that the choice of ligand can have dramatic effects on which pathway is being followed but very rarely are the reasons for this selectivity understood. The synthesis of new acyclic diaminocarbenes was developed and a study of the ligand effects on the regioselectivity of a gold-catalyzed domino enyne cyclization hydroarylation reaction and a Nazarov cyclization was undertaken. New chiral acyclic diaminocarbenes were also developed and tested along side new C3-symmetric phosphite ligands in an asymmetric intramolecular hydroamination of allenes. Structure activity correlations were developed for the potential use in further rational ligand design. The synthesis of 6a,7-dihydro-5-amino-dibenzo[c,g]chromene derivatives via a gold-catalyzed domino reaction of alkynylbenzaldehydes in the presence of secondary amines was developed. These were sent to be screened for biological activity.

Ce manuscrit débute par un panorama général de la chimie des carbènes vinyliques. Nous nous sommes ensuite intéressés à la génération de tels carbènes à partir de cyanoazétidines, qui conduisent à la formation d’amines homopropargyliques. L’extension de cette réactivité aux cyanoépoxydes nous a menés à la découverte d’une voie de synthèse d’ α-hydroxy-β-azidotétrazoles (AHBATs), qui ont fait l’objet d’une application originale en chimie de ligation. Ainsi, ces AHBATs permettent de réaliser des réactions click de CuAAC de façon orthogonale et itérative. Enfin, la dernière partie de ce manuscrit est consacré à l’étude mécanistique et à l’optimisation de la décomposition d’ α-hydroxytétrazoles en alcynes vrais. / This manuscript begins with a general description of the chemistry of alkylidene carbenes. We then studied the generation of such carbenes from 2-cyanoazetidines, leading to the formation of homopropargylamines. The extension of this reactivity to cyanoepoxides lead us to discover a way to synthesize α-hydroxy-β-azidotetrazoles (AHBATs), that appeared to have an interesting application in ligation chemistry. These AHBATs allow to realize sequential and iterative CuAAC reactions in an orthogonal manner. Finally, the last part of this manuscript describes the mechanistic and optimization studies of the decomposition of α-hydroxytetrazoles into alkynes.

La découverte et l’étude de versions stables d'intermédiaires réactionnels, tels que les radicaux ou les carbènes stables, ont eu un impact profond sur la chimie moderne. Non seulement ces composés ont permis, sur le plan académique, l’émergence de nouveaux concepts et une compréhension plus approfondie d’importantes questions fondamentales, mais ils ont également ouvert la voie au développement d’applications pratiques originales et innovantes.Les oxyallyles sont des intermédiaires réactionnels typiques, postulés dans plusieurs transformations chimiques mais longtemps considérés comme non-isolables, voire non-observables. Cependant, des résultats préliminaires à nos travaux démontraient que la conception de versions stables était envisageable grâce à l’introduction de groupements donneurs aminés.Ce travail de thèse a porté sur le développement de méthodologies de synthèse de motif organiques de type 1,3-di(amino)oxyallyles. Le premier chapitre bibliographique résume 40 ans de tentatives d’observation d’oxyallyles transitoires ou de dérivés stabilisés.Le chapitre suivant décrit nos efforts pour synthétiser des dérivés 1,3-di(amino)oxyallyles par oxydation directe de sels de vinamidiniums. Cette approche a conduit à la génération du radical cation du tetrakis(dimethylamino)oxyallyle qui, malgré un faible encombrement stérique, est persistent plusieurs heures en solution aérée.La troisième partie explore une méthodologie alternative, basée sur l’utilisation de groupes protecteurs. Cette voie complémentaire a notamment permis la synthèse et la caractérisation de dérivés d’oxydes de pyrazolium, des colorants proposés et étudiés théoriquement, mais jamais synthétisés et dont la possible existence était mise en doute.Enfin la dernière partie se consacre à la conception de carbènes stables originaux et de leurs dérivés, avec en perspective leur utilisation comme ligands redox actifs. En particulier, nous décrivons la synthèse et l’étude du premier 1,3-pyrimidinium-2-ylidène stable, ainsi que l’oxyde correspondant : formellement un oxyallyle fusionné à un amidinium, mais parfaitement stable à l’air. / The discovery and the study of stable versions of reactive intermediates, such as radicals or carbenes, have had a deep impact on modern chemistry. Those compounds have not only allowed for the rise of new academic concepts and deeper understanding of fundamental questions, but they also paved the way for the development of innovative and original applications.Oxyallyls are typical elusive intermediates, postulated in several chemical reactions, though they had been considered as non-isolable, and even non-observable for a long time. However, preliminary results to our work demonstrated that enhanced stabilization could be achieved by introducing electron-donating amino groups.This work focused on the development of a methodology for the synthesis of organic 1,3-di(amino)oxyallyl patterns. The first chapter summarizes 40 years of attempts for the observation of transient oxyallyls and stabilized derivatives.The following chapter describes our efforts to synthesize 1,3-di(amino)oxyallyl derivatives by direct oxidation of vinamidinium salts. This approach afforded the generation of the tetrakis(dimethylamino)oxyallyl radical cation, which, despite a small steric hindrance is persistent for hours in aerated solutions.The third part explores an alternative methodology, based on the use of protective groups. It enabled the synthesis and the characterization of a pyrazolium oxyde derivative, which has been proposed theoretically, but never synthesized, and whose existence was even questioned.Finally, the last chapter describes the conception of original stable carbenes and their derivatives, with their use as redox non-innocent ligands in perspective. In particular, we report the synthesis and the study of the first stable 1,3-pyrimidinium-2-ylidene, as well as its corresponding oxide: formally an oxyallyl fused with an amidinium, but perfectly stable towards air.

With its unrivaled versatility and atom economy, olefin metathesis is arguably the most powerful catalyst methodology now known for the construction of carbon-carbon bonds. When compared to palladium-catalyzed cross-coupling methodologies, however, catalyst productivity lags far behind, even for the “robust” ruthenium metathesis catalysts. Unexpected limitations to the robustness of these catalysts were first widely publicized by reports describing the implementation of metathesis in pharmaceutical manufacturing. Recurring discussion centered on low catalyst productivity resulting from decomposition of the Ru catalysts by impurities, including ppm-level contaminants in the technical-grade solvent. Over the past 7 years, a series of mechanistic studies from the Fogg group has uncovered the pathways by which common contaminants (or indeed reagents) trigger catalyst decomposition. Two principal pathways were identified: abstraction of the alkylidene or methylidene ligand by nucleophiles, and deprotonation of the metallacyclobutane intermediate by Bronsted base. Emerging applications, however, notably in chemical biology, highlight new challenges to catalyst productivity. The first part of this thesis emphasizes the need for informed mechanistic insight as a guide to catalyst redesign. The widespread observation of a cyclometallated N-heterocyclic carbene (NHC) motif in crystal structures of catalyst decomposition products led to the presumption that activation of a C-H bond in the NHC ligand initiates catalyst decomposition. Reducing NHC bulk has therefore been proposed as critical to catalyst redesign. In experiments designed to probe the viability of this solution, the small NHC ligand IMe4 (tetramethylimidazol-2-ylidene) was added to the resting-state methylidene complexes formed in metathesis by the first- and second-generation Grubbs catalysts (RuCl2(PCy3)2(=CH2) GIm or RuCl2(H2IMes)(PCy3)(=CH2) GIIm, respectively). The intended product, a resting-state methylidene species bearing a truncated NHC, was not formed, owing to immediate loss of the methylidene ligand. Methylidene loss is now shown to result from nucleophilic attack by the NHC – a small, highly potent nucleophile – on the methylidene. Density functional calculations indicate that IMe4 abstracts the methylidene, generating the N-heterocyclic olefin H2C=IMe4. The latter is an even more potent nucleophile, which attacks a second methylidene, resulting in liberation of [EtIMe4]Cl. These findings report indirectly on the original question concerning the impact of ligand truncation. The ease with which a small, potent nucleophile can abstract the key methylidene ligand from GIm and GIIm underscores the importance of increasing steric protection at the [Ru]=CH2 site. This chemistry also suggests intriguing possibilities for efficient, selective, controlled methylidene abstraction to terminate metathesis activity while leaving the “RuCl2(H2IMes)(PCy3)” core intact. This could prove an enabling strategy for tandem catalysis applications in which metathesis is the first step. The second part of this thesis, inspired by the potential of olefin metathesis in chemical biology, focuses on the impact of hydroxide ion and water on the productivity of phosphine-free metathesis catalysts. In reactions with the important second-generation Hoveyda catalyst HII, hydroxide anion is found to engage in salt metathesis with the chloride ligands, rather than nucleophilic attack. The resulting Ru-hydroxide complex is unreactive toward any olefins larger than ethylene, while ethylene itself causes rapid decomposition. Proposed as the decomposition pathway is bimolecular coupling promoted by the strong H-bonding character of the hydroxide ligands. Lastly, the impact of the water on Ru-catalyzed olefin metathesis is examined. In a survey of normally facile metathesis reactions using state-of-the-art catalysts, even trace water (0.1% v/v) is found to be highly detrimental. The impact of water is shown to be greater at room temperature than previously established at 60 °C. Preliminary evidence strongly suggests that the mechanism by which water induces decomposition is temperature-dependent. Thus, at high temperature, decomposition of the metallacyclobutane intermediate appears to dominate, but this pathway is ruled out at ambient temperatures. Instead, water is proposed to promote bimolecular decomposition. Polyphenol resin, which can sequester water by H-bonding, is shown to offer an interim solution to the presence of trace water in organic media. These findings suggest that major avenues of investigation aimed at reducing intrinsic catalyst decomposition may likewise be relevant to the development of water-tolerant catalysts.