Une méthode simple et efficace a été développée pour la préparation de ligands bifonctionnels associant les motifs phosphine ou phosphite d'une part, et carbène Nhétérocyclique(NHC) ou imidazolium d'autre part. Dans un premier temps, une série de ligands diphénylphosphine-carbène chiraux portant un centre stéréogène en a de la phosphinea été développée à partir b-hydroxyesters. Une famille de ligands a ainsi été développée afin d'évaluer l'influence de l'encombrement stérique de différents groupements alkyles en a de la phosphine et de la nature des groupements aromatiques portés sur l'imidazole sur leur activité catalytique. L’étude s’est ensuite étendue à la synthèse de ligands de type dialkylphosphine carbène et phosphite-carbène. Ces différents ligands ont été complexés avec des métaux tels que l’iridium ou le rhodium de manière à en étudier l’activité en hydrogénation asymétrique. / A straightforward method for the preparation of new bidentate ligands containing aphosphine or a phosphite and a carbene function was developed. Different phosphorus-imidazolium compounds were prepared according to this method. First, diphenylphosphine-NHC ligands featuring a stereogenic center a to the phosphine were synthesized from b-hydroxyesters. This strategy was then extended to the preparation of phosphite-imidazoliumand dialkylphosphine-imidazolium compounds. Complexation of these phosphorus-NHCligands with different metals like Ir or Rh was performed in order to study there catalytic properties in asymmetric hydrogenation.

Doctor of Philosophy / Department of Chemistry / Stefan Bossmann / My thesis is divided into two parts. The first part is focused on studies of N-heterocyclic carbene (NHC) palladium(IV) intermediates, which are involved in oxidative addition mediated C-C, and C-O bond formation processes as well as in C-Cl bond forming reactions via a reductive elimination process. Bis-NHC-Pd(II) complexes have been reported as effective catalysts to mediate direct conversion of methane into methanol. However, a H-D exchange study revealed that the bis-NHC-Pd(II) complexes are not the active species responsible for the C-H bond activation reaction. This unexpected result implies that the high oxidation state bis- NHC-Pd(IV) species may be the real catalyst! The oxidative addition of methyl iodide to the bis- NHC-Pd(II)-Me2 complex led to the successful observation of the formation of a transient trimethyl bis-NHC-Pd(IV) intermediate by both 1H-NMR and 13C-NMR spectroscopy. Different oxidants such as O2, PhI(OAc)2, PhI(OTFA)2 and Cl2 reacted with the bis-NHC-Pd(II)-Me2 complex, and competitive C-C and C-O bond formations, as well as C-C and C-Cl bond formations were observed. Dioxygen triggered C-C bond formation under dry condition and both C-C and C-O bond formation in the presence of H2O gave strong indications that the bis-NHCPd( II)-Me2 complex can be oxidized to a bis-NHC-Pd(IV) intermediate by dioxygen. The reaction between the hypervalent iodine regents PhI(OAc)2 and PhI(OTFA)2 and the bis-NHCPd( II)-Me2 complex gave only reductive elimination products. Therefore, this system can act as a model system, which is able to providing valuable information of the product forming (functionalization) step of the C-H bond activation system. The reaction between chlorine and the bis-NHC-Pd(II)-Me2 complex resulted in a relatively stable bis-NHC-Pd(IV)-Cl4 complex, which was characterized by 1H-NMR spectroscopy and mass spectroscopy. The structure of bis- NHC-Pd(IV)-Cl4 was unambiguously established by X-ray crystallography. The second part of this thesis describes the synthesis of functionalized bimagnetic core/shell iron/iron oxide nanoparticles for the treatment of cancer. Biocompatible dopamineoligoethylene glycol functionalized bimagnetic core/shell Fe/Fe3O4 nanoparticles were prepared via ligand exchange, and purified by repeated dispersion/magneto-precipitation cycles. A porphyrin (TCPP) has been tethered to the stealth nanoparticles to enhance their uptake by tumor cells and (neural) stem cells. The stealth nanoparticles have been delivered in a mouse model to tumor sites intravenously by using the EPR (enhanced permeation and retention) effect. Magnetic hyperthermia proved to be very effective against B16-F10 mouse melanomas in Charles River black mice. After hyperthermia, the nanoparticles have shown a significant effect on the growth of tumor (up to 78% growth inhibition).

The bidentate ligand 1,2-bis(ditertbutylphosphinomethyl)benzene has been shown to be a very efficient catalyst for operating the alkoxycarbonylation of alkenes and unsaturated esters and carboxylic acids giving a very high selectivity to the linear product with very few exceptions to this general rule. Due to the increasing prices of petroleum feedstock and petroleum-derived chemicals, the preparation of chemicals starting from renewable resources and waste products from the industry becomes an interesting alternative. Fatty acids and fatty esters, due to the existence of one or more unsaturation in their alkyl chain are subjected to the alkoxycarbonylation reactions in presence of 1,2-bis(ditertbutylphosphinomethyl)benzene, palladium, methane sulfonic acid, carbon monoxide and methanol, yielding diesters with a long carbon chain (up to 19 carbon atoms). The diesters are shown to be readily prepared from unpurified olive, rapeseed or sunflower oils as well as from tall oil. In the last case triesters are also formed. The diesters are subjected to hydrogenation in the presence of 1,1,1-tris(diphenylphosphinomethyl)ethane, ruthenium and hydrogen, in a mixture of dioxane and water at high temperature, yielding the corresponding diols. The resulting products of the reactions are monomers for preparing polyesters having the potential to replace some existing petroleum-based polymers (for instance polyethylene). The aminocarboxylation reaction in the presence of the same palladium/1,2-bis(ditertbutylphosphinomethyl) benzene catalyst, in the presence of aniline, 2{naphthol and potassium iodide in diethylether, is employed for preparing esteramides, which are subjected to hydrogenation. Aromatic polyamides are prepared by melting together an aromatic diamine and diacids obtained from methoxycarbonylation. Finally, N-Heterocyclic Carbene (NHC) ligands are employed for preparing new palladium complexes which are used in the Suzuki-Miyaura cross-coupling reaction in a water/isopropanol mixture. Other complexes based on copper are employed for developing an inexpensive transmetallation reaction for transferring a NHC ligand from copper to palladium and gold.

Chapter one is an introduction to the less common coordination and oxidation chemistry of palladium; complexes containing Pd-OR, Pd-NR2 and those in the oxidation states of +IV. An outline of PdII/IV catalysed ligand-directed oxidative functionalisation is also included. Chapter two covers the design and synthesis of a range of tethered N-heterocyclic carbene (NHC) complexes of Pd. In addition, the syntheses of a number of new tethered NHC ligands are described. The use of Density Functional Theory (DFT) to model the complexes in this thesis was explored. Chapter three describes the synthesis and characterisation of PdIV halide complexes. The relevance of these compounds to PdII/IV catalysed ligand-directed oxidative functionalisation is explored. DFT was used to probe the reaction pathway for N-bromosuccinimide and iodobenzene dichloride. Chapter four examines reactions with oxidants used to form C-O and C-C bonds. The reaction pathway for iodobenzene diacetate was investigated using DFT. Chapter five contains experimental details and characterising data for the compounds reported.

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Carbonyl complexes of Ni(0) incorporating two N-heterocyclic carbenes of the type Ni(CO)2(NHC)2 (NHC = ICy [N, N'-bis(cyclohexylimidazol)-2-ylidene], IMes [N, N'- bis(2, 4, 6-trimethylphenyl)-imidazol)-2-ylidene]) have been prepared. The complexes Ni(CO)2(ICy)2 (8) and Ni(CO)2(IMes)2 (9) have been synthesized and characterized by single crystal X-ray diffraction. The enthalpy of substitution reactions of Ni(CO)2(NHC) (NHC = ItBu [N, N'-bis(tert-butylimidazol)-2-ylidene], IAd [N, N'-bis(1- adamentylimidazol)-2-ylidene]) with NHC and tertiary phosphine ligands leading to the formation of Ni(CO)2(L)2 (L = NHC, PR3) complexes have been determined. The solution calorimetric investigations reiterate the greater electron donating property of the NHC ligands compared to tertiary phosphines. Thermochemical studies of the substitution reactions of Ni(CO)2(NHC) (NHC = ItBu, IAd) forming complexes (8) and (9) led to the determination of average bond dissociation energy of Ni-NHC (NHC = ICy, IMes) and Ni-P (P = PCy3, PPh3, P(p-Tol)3, P(m-Tol)3).

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The chapter one introduces the reported examples of rare earth metal (RE) complexes with different oxidation states. It also reviews the synthesis and reactivity study of N-heterocyclic carbene (NHC) supported transition metal and RE metal complexes. Chapter two focusses on the synthesis and characterisation of a series of tetraaryloxide Ce and Pr complexes. With the reaction of bulky tetraphenol proligand H4LR(R = P, PT, M) with four equivalents of KN"(N" = N(SiMe3)2), a dimerised complex of [K4LP]2(thf)11 was synthesised and characterised. The salt metathesis reactions of this complex with RECl3(thf)2 afford bimetallic aryloxide complexes of K2L2RE2(thf)11 (RE = Ce, Pr), which display divergent structures under different conditions. Reactions of the CeIII complex of K2L2Ce2(thf)11 with a variety of oxidants(I2, CuCl2 and O2, etc.) lead to the oxidation of CeIII to CeIV, affording purple ceric dimer of L2Ce2. The reaction of the PrIII complexes with I2 under 60 °C affords a mixture from which PrIII iodide (LPr2I2) has been isolated and characterised. This chapter also discusses the reactivity of the bimetallic aryloxide complexes towards different substrates, such as MeLi, KC8 and KBn (Bn = benzyl). Bimetallic complexes of L(REX)2(py)8 (RE = Ce, Pr; X = Cl, BH4) are synthesised and characterised. The preliminary study on the copolymerization of cyclohexene oxide (CHO) and CO2 is conducted for CeIII and PrIII complexes. Chapter three details the work on two different types of NHC ligand. The first ligand is the β-ketoimidazolinium salts H2LBr {L = RC(O)CH2{CH[NCH2CH2NMes], R = tBu, naphth} which reacts with MHBEt3 (M = Na, K) to form carbene-borane adducts RC(O)CH2{C(BEt3[NCH2CH2NMes]}. This type of reactivity differs from the previous work on imidazole derivatives. The possible mechanism of these reactions is provided and discussed. The other ligand is p-aryloxy-tethered imidazolinium salt H2LX (L = N-3,5-di-tert-butyl-4-hydrooxyphenyl-N’-mesityl-imidazolinium, X = Cl, Br, PF6 ), which have been synthesised and characterised. The reactions of these salts with MN"(M = Na, K) enabled the characterisation of polymerised complexes of [NaL]n and [KL(thf)2]n. The yttrium complex YL3 is synthesised and its reactivity towards small molecules such as boranes, CO2 and CS2 is discussed. Chapter four presents the primary results on the study of macrocyclic NHC based cyclophane ligand H6LPF6 (L = calix[4]imidazolylidene[2]pyrazolato). Investigations on the reactivity of the ligand towards different bases (NaN", KN", KBn etc.) are examined and subsequent metathesis reactions with RE complexes are explored. Chapter five concludes the work presented in this thesis. Chapter six contains all experimental and characterisation details.

Au début de ces travaux, peu d’études avaient été faites sur la complexation des carbènes N-hétérocycliques avec des métaux oxophiles, électropositifs et à hauts degrés d’oxydation tel que les métaux du groupe 13. L’optimisation de voies de synthèse a permis d’étendre le nombre de complexes de types NHC-MIII (M = aluminium, gallium et indium), ainsi qu’à des complexes cationiques. L’association de ces précurseurs avec des NHCs plus encombrés a permis l’observation de réactivités sans précédent (complexes anormaux, paires de Lewis frustrées, dicarbènes N-hétérocycliques). Dans un second temps, la réactivité inhabituelle des ligands NHCs a permis l’isolation d’analogue au réactif de Tebbe, très actifs en méthylénation de dérivés carbonyles. / At the beginning of this work, few studies had been performed on the complexation of N-heterocyclic carbenes with oxophilic metals, in high oxidation states such as group 13 metals. The synthetic routes optimization has extended the number of complexes-type NHC-MIII (M = aluminum, gallium and indium), and the corresponding cationic complexes. The combination of these precursors with sterically congested NHCs allowed the observation of unprecedented reactivities (abnormal complexes, Frustrated Lewis Pairs, N-heterocyclic dicarbenes). In a second step, the unusual reactivity of NHC ligands has allowed the isolation of analogues of the Tebbe’s reagent, formed to be very active in the methylenation of carbonyl compounds.

The development of procedures for the synthesis of valuable organic molecules constitutes an important part of chemistry. The goal of improving the efficiency of existing methodologies can be fulfilled by use of metal catalysts. Recent developments in the field of homogeneous gold catalysis have contributed to these efforts and continued investigations assure future innovations. Chapter 1 summarises the properties of gold and ligand-supported gold(I) complexes and demonstrates how a detailed understanding of its reactivity and possible bonding interactions with various substrates facilitates the development of well-defined catalytic systems. Particular attention is given to N-heterocyclic carbenes, highly tunable ligands that stabilise a wide range of different transition metal complexes. Three chapters describe syntheses and studies of known and new complexes. Chapter 2 discusses expedient syntheses of key NHC-gold(I) complexes and catalysts. Chapter 3 constitutes studies to the behaviour of the commonly used tetrafluoroborate counterion in a particular IPrCl -gold(I) complex. Chapter 4 de- scribes the synthesis of a range of IPr-gold(I) carbanion complexes from the widely studied IPr-gold(I) hydroxide synthon, the study of their properties and exploration of their reactivity. Catalytic applications in transformations of alkynes and alcohols are described in the last three chapters. Chapter 5 details the development of efficient NHC-gold(I)-catalysed procedures for the synthesis of vinyl ethers through addition reactions of aliphatic and benzylic alcohols to alkynes. Benzylic alcohols were found to undergo gold-catalysed dehydration under specific conditions and Chapter 6 discloses the NHC-gold(I)-catalysed dehydrative formation of ethers from phenols and benzylic alcohols. Appendix A describes preliminary explorations to the complimentary use of Brønsted acidic compounds as catalysts for the formation of products with new C – C bonds from benzylic alcohols and phenols.