This thesis describes the catalysed addition of X-H bonds (X = S, O and N) to alkynes using a range of novel rhodium(I) and iridium(I) complexes containing hybrid bidentate phosphine-pyrazolyl, phosphine-imidazolyl and phosphine-N heterocyclic carbene (NHC) donor ligands. The synthesis of novel bidentate phosphine-pyrazolyl, phosphine-imidazolyl (P-N) and phosphine-NHC (PC) donor ligands and their cationic and neutral rhodium(I) and iridium(I) complexes [M(P N)(COD)]BPh4, [M(PC)(COD)]BPh4, [Ir(P-N)(CO)2]BPh4 and [M(P-N)(CO)Cl] were successfully performed. An unusual five coordinate iridium complex with phosphine-NHC ligands [Ir(PC)(COD)(CO)]BPh4 was also obtained. Seventeen single crystal X-ray structures of these new complexes were determined. A range of these novel rhodium and iridium complexes were effective as catalysts for the addition of thiophenol to a variety of alkynes. Iridium complexes were more effective than rhodium analogues. Cationic complexes were more effective than neutral complexes. Complexes with hybrid phosphine-nitrogen donor were more effective than complexes containing bidentate nitrogen donor ligands. An atom-economical, efficient method for the synthesis of cyclic acetals and bicyclic O,O-acetals was successfully developed based on the catalysed hydroalkoxylation. Readily prepared terminal and non-terminal alkyne diols were cyclised into bicyclic O,O-acetals in quantitative conversions in most cases. The efficiency of a range of rhodium and iridium complexes containing bidentate P-N and PC donor ligands as catalysts for the cyclisation of 4-pentyn-1-amine to 2-methyl-1-pyrroline varied significantly. The cationic iridium complexes with the bidentate phosphine-pyrazolyl ligands, [Ir(R2PyP)(COD)]BPh4 (2.39-2.42) were extremely efficient as catalysts for this transformation. Increasing the size of the substituent on or adjacent to the donor led to improvement in catalytic activity of the corresponding metal complexes. The mechanism of the catalysed hydroalkoxylation was proposed to proceed by the initial activation of the alkyne via ?? coordination to the metal centre. The ?? binding of both aliphatic and aromatic alkynes to [Ir(PyP)(CO)2]BPh4 (2.44) was observed by low temperature NMR and no reaction between 2.44 and alcohols was observed. In contrast, the facility in which thiol and amine oxidatively added to 2.44 led the proposal that in the hydrothiolation and hydroamination reaction, the catalytic cycle commences with the activation of the X-H bond (X = S, N) by an oxidative addition process.

The industrial revolution came with its downside of emission of greenhouse gases into the atmosphere. The NOAA reported in 2019 that, of the greenhouse gases emitted into the atmosphere, CO2 contributed to about 80% of the increased greenhouse gases hence the need for CO2 Sequestering and Storage (CSS) and ultimately leading to Carbon Capture and Recycling (CCR) as a viable option to convert CO2 into useful forms. The race to find the best catalyst for CCR has led to the synthesis of many organometallic compounds. Pincer complexes catalyzed CO2 reduction has gained notoriety recently because of the tunability and robustness without causing any alteration in their overall coordination geometry. Different metals and pincer motifs have been reported for the electrocatalytic and photochemical reduction of CO2. Chapter I introduces the broader project impact, N-heterocyclic carbene concepts, pincer chemistry, iron pincer chemistry, and N-heterocyclic pincer complexes of Fe for a comprehensive perspective. Chapter II addresses the scarcity of iron based NHC pincer complexes due to deprotonation challenges and octahedral coordination preferences. Bulky substituents like mesityl, adamantly, or DIPP enable mono-ligated pincer complexes by hindering ligand encapsulation, leaving no open coordination site. In-situ metalation / transmetalation, and isolated CCC-NHC Zr complexes are presented along with a method to convert between mono-ligated and bis-ligated complexes. Chapter III explores L-type ligands' reactivity to prevent ligand reorganization around the Fe center from Chapter I. Chapter IV covers CCC-NHC Fe pincer complexes' synthesis, characterization, and transient absorption studies of bis-ligated complexes. Characterization of the CCC-NHC pincer Fe complexes in Chapter I-IV were carried out using 1H and 13C NMR spectroscopy, ESI-TOF MS, EA (Elemental Analysis), cyclic voltammetry, and X-ray diffraction. Chapter V discusses catalytic experiments and data consistent with preliminary CO2 reduction with mono-ligated CCC-NHC pincer complexes.

The N-heterocyclic carbene (NHCs) based pincer ligands field is still in its infancy after decades. They are known for their applications in organocatalysis, coordinating with transition metals and p-block elements, catalysis, and material chemistry. Among all NHCs, CCC-NHC-based on late-transition metal complexes were first developed by our group in 2005 with a unique metalation/transmetalation strategy. Our group also designed the chiral version of these CCC-NHC ligands to synthesize its metal complexes. However, their asymmetric catalytic applications were unknown. Wanting to expand on this work, we first successfully synthesized achiral CCC-NHC pincer complexes and their new catalytic application, as it is economically cheaper than directly working on developing a chiral version for catalysis. Then, different chiral CCC-NHC salts were synthesized based on different chiral arms and N-substituents on NHCs to modify their steric hindrance and electronic structure properties. These precursors were used for their enantioselective application in nucleophilic catalysis. In Chapter II, we will discuss the synthesis of the CCC-NHC pincer Ir (III) dimer complex and its first catalytic application in C−H functionalization of N-methylindoles with alpha-aryl-alpha-diazoacetates at the C-3. The best reaction conditions involve a combination of catalysts and substrates in a specific order. It resulted in the activation of the C-H bond with the formation of a new C-C bond to generate alpha-aryl-alpha-indolyl acetates with more than 99% conversion at room temperature without requiring any additives. The substrate scope and limitations of N-methyl indoles and diazoacetates were also explored. Chapter III will focus on a new modified synthetic route to synthesize and characterize chiral CCC-NHC chloride salts in a shorter synthetic route than the known one. The metalation/transmetalation of chiral CCC-NHC ligands with late transition metals and the initial attempt in asymmetric catalysis will be discussed in Chapter IV. Chapter, V, demonstrated nucleophilic catalysis of CCC-NHC precursors in benzoin condensation of aldehyde. The study started with the evaluation of fifteen different achiral bis-CCC-NHC salts based on triazole, imidazole, and benzimidazole. Further studies with chiral CCC-NHC salts also resulted in more than 99% conversion and 99% ee in benzoin products. The substrate scope of benzaldehyde with different substituents was also explored

This thesis describes our physical organic and mechanistic investigations into N Heterocyclic Carbene (NHC) mediated organocatalytic transformations, through a collaboration with the research group of Dr AnnMarie O'Donoghue and PhD student Richard Massey at Durham University. Initial research focused upon the determination of kinetic acidities and associated pKₐ values for a range of triazolium salts using C(3) H/D exchange, monitored by ¹H NMR spectroscopy. Estimates for pKₐ values in the range 16.6 17.4 were obtained, which are some ~2 and ~3 5 pK units lower than analogous imidazolium and thiazolium species respectively, with modest N substituent (0.3 pK units) effects observed. At lower pD values, an altered pD dependence indicates a dicationic triazolium species is formed (through N(1) protonation) with an estimated pKₐᴺ¹ of -0.2-0.5 and C(3) H pKₐ values at least 2 units lower than their monocationic analogues. This methodology was subsequently extended to mesoionic NHCs, where pKa values of 23.0 27.1 for a range of triazolium and 30.2 31.0 for a range of imidazolium salts were estimated. A detailed study of the NHC catalysed intramolecular Stetter reaction was also undertaken using ¹H NMR spectroscopy. A range of 3 (hydroxybenzyl)azolium salts (adducts), formed from the addition of NHC to aldehyde were isolated, enabling the generation of reaction profiles and the determination of rate constants. The reaction proceeds via rapid and reversible adduct generation, followed by rate limiting Breslow intermediate formation, with electron withdrawing N aryl substituents increasing the rate of product formation. Consistent with rate limiting deprotonation, deuterium exchange studies of O methylated adduct analogues found electron withdrawing N-aryl units gave faster exchange. Examination of the equilibrium constants for adduct formation revealed that both in the case of NHCs bearing 2,6 disubstituted N aryl units and aldehydes bearing a 2 ether substituent, the equilibrium position is significantly shifted towards adduct. Finally, studies at sub-stoichiometric NHC concentrations, monitored by HPLC, imply the reaction is first order with respect to NHC precursor, but zero order in aldehyde, again indicative of rate limiting deprotonation.

N-heterocyclic carbenes (NHCs) have become a very popular class of ligands, which has found uses in numerous catalytic applications. The use of such compounds in combination with phosphorus-based ligands within metal complexes has enabled the design of very active yet robust catalytic systems. The following chapters will describe the design of novel well-defined palladium- and ruthenium-based pre-catalysts featuring a NHC and a phosphorus-based ligand, referred at as mixed ligand systems. Such species were employed in catalysis where their properties appeared highly beneficial, uses at low catalysts loading and under harsh conditions were then envisioned. The preparation of a series of well-defined palladium mixed NHC/phosphine species is presented in chapter 2. Their catalytic activity in the aqueous Suzuki-Miyaura reaction of aryl chlorides and boronic acids, using low catalyst loadings, is described. The observation of catalytic activity of the latter systems in the hydration of nitriles prompted us to further investigate this reactivity. This reaction appeared to be operative in the absence of palladium species and could be performed under base-catalysed conditions, which was studied in detail and depicted in chapter 3. The combination of a NHC and a phosphite ligand in ruthenium olefin metathesis pre-catalysts has been underexplored. Preliminary results showed that such species could be readily prepared and presented an unusual geometry and a high catalytic activity. Variations in phosphite-containing ruthenium olefin metathesis pre-catalysts are presented. Chapter 4 describes the investigation of various Schrock carbene moieties in such architectures, as well as their implications in structure and catalysis. Chapter 5 depicts attempts to design olefin metathesis Z-selective pre-catalysts by inserting a chelating NHC moiety within phosphite-containing ruthenium species. This dissertation concludes on the potential of such mixed species in catalysis, and armed with the new knowledge provided by this work, proposes potential developments of such chemistry in the design of always more robust and active catalytic systems.

Les carbènes N-hétérocycliques (NHC) sont utilisés comme ligands pour les métaux de transition. Les complexes résultants présentent principalement des applications en catalyse, ainsi que dans la conception de nouveaux candidats médicaments. Dans ce travail, nous discuterons une simplification des méthodes de synthèse des sels d’imidazoliniums, ainsi que des complexes Cu- et Ag-NHC. L’ammoniaque est utilisé ici à la fois comme milieu solubilisant des espèces métalliques et comme base pour la déprotonation des sels d’imidazoli(ni)ums fournissant une métallation douce, rapide et simple. La fonctionnalisation des NHC, dans des positions définies, permet une modulation de certaines de leurs caractéristiques sans impacter les propriétés remarquables de leurs complexes. De nouvelles méthodes de fonctionnalisation, par cycloaddition azoture-alcyne en périphérie des noyaux aromatiques, ont été mises au point. Ceci mène à l’introduction de trois stratégies synthétique : pré-, post- et auto-fonctionnalisation. La stratégie de pré-fonctionnalisation de précurseurs permet l’accès à des métallo-NHC du groupe 11, dont les propriétés de solubilité peuvent être facilement modifiées. Des réactions thermiques d’Huisgen et de SPAAC sont réalisables directement sur les complexes Au-NHC modifiés par des azotures, et sont désignés comme post-fonctionnalisation. Des réactions dites d’auto-fonctionnalisations entre un complexe Cu-NHC possédant un azoture et des alcynes divers, permettent l’introduction, par exemple, de biomolécules sensibles sans étapes de protection/déprotection. Enfin, les complexes Cu-NHC fonctionnalisés avec des groupements hydrosolubilisants ont été étudiés en tant que catalyseurs de cycloaddition de CuAAC dans des milieux biocompatibles, tandis que les Ag-NHC fonctionnalisés avec des groupements lipophiles présentent une activité antibactérienne. / N-heterocyclic carbenes (NHCs) have been used very frequently as ligands for the preparation of transition metal-based catalysts as well as drug candidates. This work will present a simplification of imidazoliniums synthesis and a new preparation of Ag-, Cu-NHC complexes. Aqueous ammonia will be used for the solubilisation of metallic species and as a base for the deprotonation of imidazoli(ni)um salts providing a mild, quick and easy metallation procedure. The functionalisation of NHC ligands, in definite positions, allows the modulation of some of their characteristics without interfering with the remarkable properties of their complexes. New functionalisation strategies by azide-alkyne cycloaddition reaction at the periphery of aromatics cores, were developped. This can be described by the following three synthetics strategies: pre-, post- and auto-functionalisation. Pre-functionnalisations strategy of precursors allows the synthesis of coinage metal-NHC complexes, for which variation of solubility is easily obtained. Thermal Huisgen reactions and SPAAC are achievable on the Au-NHC azide modified complexes directly, in a post-functionalisation pathway. Furthermore, the post-functionnalisation strategy was extended to Cu-NHC complexes resulting in an auto-functionalisation process. This allowed subsequently the introduction of sensitive biomolecules without protection/deprotection steps. Finally, water soluble Cu-NHCs complexes were used as CuAAC catalyst in bio-compatible media. Lipophilic Ag-NHCs complexes were tested as antibacterials (antibiofilm and growth inhibition activities).

京都大学 / 0048 / 新制・課程博士 / 博士(薬学) / 甲第18204号 / 薬博第794号 / 新制||薬||237(附属図書館) / 31062 / 京都大学大学院薬学研究科創薬科学専攻 / (主査)教授 高須 清誠, 教授 竹本 佳司, 教授 川端 猛夫 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

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A series of 24 new photoluminescent symmetric and unsymmetric -NHC pincer Pt complexes was synthesized and characterized, including collection of their 195Pt NMR chemical shifts. In total 18 new X-ray crystal structures, and photophysical studies of these photoluminescent -NHC pincer Pt complexes are reported. -NHC pincer Pt complexes were synthesized and characterized using new -NHC pincer based proligands [(RChetChetCRH3)X2, X = Cl, Br, or BPh4, where het represents imidazolyl, benzimidazolyl, and 1,2,4-triazolyl moieties; R = n-butyl, 3,3-dimethylbutyl, n-hexyl] as starting materials. A new method to synthesize Pt-Cl complexes to prevent halogen mixing was developed using tetraphenylborate salts as proligands. -NHC pincer complexes Pt(II) were oxidized to Pt(IV) complexes by reaction with Br2, I2, or iodobenzene dichloride. Photophysical studies showed emission of blue to red-orange color range for the Pt(II) complexes when irradiated with long wavelength UV light (360 nm). No visible emission for Pt(IV) complexes was observed upon irradiation at 360 nm. The tunable photoluminescence of the synthesized -NHC pincer Pt(II) complexes can be used as the materials for OLEDs. Parameters and scales that provide understanding of steric and electronic effects are essential to predicting properties, and, therefore, to systematically designing new ligands. Meridional tridentate pincer ligands are neither conveniently nor accurately described by existing options. A scale has been developed based on 195Pt NMR chemical shift that is reflective of the total donor ability of a multi-dentate ligand in a square planar complex and that does not suffer from cis/trans stereochemical issues. This scale, Platinum Electronic Parameter (PtEP) and defined as PtEP = -(195Pt NMR shift) in CDCl3 revealed significant deviations of -NHC pincer ligands, PCP and POCOP donor abilities from predicted extrapolations using existing TEP parameters. This initial data set demonstrates the applicability and broad potential of the PtEP scale.

No description available.