Dissertationen zum Thema „Palladium - N - heterocyclic carbene“

The use of ligand in transition-metal catalysed reactions has had a considerable impact. The present manuscript aims at showing the influence of ligands in the palladium catalysed Suzuki-Miyaura cross-coupling reaction. In chapter one, the mechanism of this reaction will be described based on the numerous contribution published in the literature. It will be shown that the electronic and steric properties of the ligands have a huge repercussion on the catalytic activity of the metal. In the second chapter, the electronic and steric properties of the widely used Buchwald-phosphine ligand will be investigated. For this purpose, bis-carbonyl iridium(I) complexes were synthesized and their characterization allowed determining their TEP (Tolman electronic parameter) and their buried volume %V[subscript(bur)]. Then three next chapters of this thesis will focus on the syntheses and characterizations of new palladium complexes bearing N-heterocyclic carbenes (NHC). Their design was made in a view to obtain high activity in cross coupling reaction, particularly in the Suzuki-Miyaura cross coupling. Their activation under the catalytic conditions leads to the formation of palladium(0) species that can be mono- or bis-ligated. The influence of the ligand on the catalyst activity will be discussed. A palladium(II) precatalyst leading to mono-ligated active species will be described. Its activity in cross-coupling is very good, since activated and non-activated aryl chlorides could be coupled with aryl boronic acids at room temperature using low catalyst loadings. Unfortunately, the catalyst activity decreased with temperature. This result showed the fragility of the mono-ligated active species. In a view to obtain more robust catalysts that can perform high turnover numbers, new palladium(II) precatalysts bearing two ancillary ligands were developed. Mixed systems NHC- phosphites and NHC-phosphines are described. NHC-phosphites precatalysts displayed very good activity, but the phosphites are unfortunately sensitive to reaction conditions, limiting their role of active species shield. NHC-phosphine bearing complexes were highly active and could perform up to 10,000 turnovers with unactivated aryl chlorides. Very interestingly, these catalysts were also able to couple benzylchlorides and allyl chlorides with a wide range of boronic acids at very low catalyst loadings. These reactions had also the great advantage to proceed in aqueous solvents at very high substrate concentration. The activation mechanism of these complexes was investigated. Dichloropalladium(II) complexes were reduced under the catalytic conditions to lead palladium(0) species. Therein, it is shown that this reduction step was rate-determining in catalysis. Some palladium(0) intermediates xxiv were synthesized and showed good to excellent activities at low temperature under the exact same conditions. They displayed high reactivity towards oxygen and moisture and have to be handled under inert atmosphere. A particular complex had the ability to react with molecular dioxygen to form a stable peroxo-complex. Interestingly, this complex displayed excellent activity in water under aerobic conditions. This system was of great advantage since the reaction could be set up under air using cheap and user-friendly reagents displaying low toxicity. Moreover, the readily available distilled water used as solvent did not require prior degassing. Symmetrical and unsymmetrical bis-NHC palladium(0) complexes were successfully synthesized. They display excellent activity in the Suzuki-Miyaura cross coupling and turnover frequencies as high as 300 could be obtained at room temperature with unactivated arylchlorides and arylboronic acids. These complexes were also found excellent catalysts for the coupling of benzylchlorides with arylboronic acids. Mechanistic studies showed that no ligand dissociation occurred during the coupling suggesting as bis-ligated active species.

The work described in this thesis is primarily focused on the synthesis and characterisation of two-coordinate zerovalent palladium complexes bearing an N-heterocyclic carbene ligand. These complexes have been assessed as pre-catalysts for coupling reactions in particular ami nation reactions involving the generation of a C-N bond. Chapter 1 presents the synthesis of complexes r, r bearing the ligand [CNCBu)(CH)2NCBu)]. An alternative synthesis for [Pd{CNCBu)(CH)2NCBu)h] 1 is reported involving reaction of [{Pd(T)3-C4H7)Clhl with sodium dimethyl malonate and carbene. Reaction of 1 with iodobenzene led to formation of a Pd(II) speCies, r , [Pd{CNCBu)(CHhNCBu)h(C6Hs)I] 2. An intermediate in the synthesis of 1, r [Pd(T)3-C4H7){CNCBu)(CHhNCBu)h(C6Hs)C] 3, has been isolated and fully characterised. Two r , mixed carbene phosphine complexes, [Pd{CNCBu)(CHhNCBu)}{P(o-tolylh}] 4 and r , [Pd{CNCBu)(CHhNCBu)} {PCY3} 1 S, have also been synthesised. Complexes 1,4 and S have been assessed as a pre-catalysts for ami nation couplings with limited success. Chapter 3 presents the r , synthesis of two complexes bearing the ligand [CN(Me)(CMe)2N(Me)]. Metal vapour synthesis was r , used to synthesise [Pd{CN(Me)(CMehN(Me)h] 6 and the diiodide complex r , [Pd{CN(Me)(CMehN(Me)hI2] 7 was also prepared. Complexes 6 and 7 were shown to have no activity as pre-catalysts in amination couplings. Chapter 4 presents the synthesis of complexes r· ~. bearing the ligand [CN(2,6-'Pr2-C6H3)(CH2hN(2,6-'PrrC6H3)]. The methodology used to synthesise r. ~. 1 was applied to the synthesis of [Pd{CN(2,6-'Pr2-C6H3)(CH2hN(2,6-'PrrC6H3)h] 8. Substitution of a phosphine ligand In [Pd {P(o-tolylh hl by carbene led to formation of r. ~. [Pd{CN(2,6-'PrrC6H3)(CH2hN(2,6-'PrrC6H3)}{P(o-tolyl)3}] 9. Complexes 8 and 9 were successfully employed as pre-catalysts for amination couplings. 4-Chlorotoluene was shown to couple to a variety of primary and secondary amines including cyclic, acyclic and aryl substituted as well as an imine. The same proceedure was also used to couple chloropyridines with morpho line Reactions were typically conducted with 2 mol% pre-catalyst and KOtBu base in dioxane at 100 °C and were found to be complete after 0.5-5 h. The isolated yields of product obtained were typically r· ~. above 95%. Reaction of 1 with [CN(2,6-'Pr2-C6H3)(CH2hN(2,6-'Pr2-C6H3)] led to formation of r \ r. ~. [Pd{CN(,Bu)(CH)2N(,Bu)} {CN(2,6-'Pr2-C6H3)(CH2hN(2,6-'Pr2-C6H3)}] 10. Complex 10 was found to be less active as a pre-catalyst for amination couplings than either 8 or 9. A copper carbene r. ~. complex [Cu {CN(2,6-'Pr2-C6H3)(CH2)2N(2,6-'Pr2-C6H3)} I] 11 was also synthesised and shown to facilitate the coupling of 4-iodotoluene with morpholine to give the coupled product in a 38% yield. Chapter 5 presents the results of some ligand substitution reactions. Complexes 1 and 8 were reacted with phosphines to give mixed carbene phosphine complexes 4, S and 9. The results obtained showed that phosphines can displace carbenes despite the strength of metal carbene bonds

Chapter 1 gives the reader a background on cross-coupling reactions, in particular palladium mediated couplings. Furthermore the importance of ligands, including phosphines and N-heterocyclic carbenes (NHC), in such cross-coupling reactions is explored. Chapter 2 provides a background to the reductive lithiation of phosphines, followed by an account of our investigation of BINAP functionalisation by means of reductive elimination.1 The reaction was examined by experimental means and through the use of density functional theory to predict 31P NMR chemical shifts. Chapter 3 provides background on the Heck reaction and selected developments over the years, with particular reference to the use of aryl chlorides in the reaction. A brief discussion of NHC based palladium complex sets the scene for our investigation of a new class of (NHC)-Pd catalysts developed by the Navarro group. Complexes of type (NHC)PdCl2(TEA) (TEA = triethylamine) have been tested for their activity in the Heck reaction, focusing on the scope of the reaction with electron-deficient aryl chlorides and electron-rich aryl bromides.2 Chapter 4 gives an account of the discovery and developments of the Sonogashira reaction. Particular attention is paid to non-classical systems such as palladium-only and copper-only protocols. Herein our investigation into the use of collaborative (NHC)-Pd and (NHC)-Cu in Sonogashira reactions is presented.3 Notable features of this system are the low catalyst loadings and the synthetically convenient conditions in which the reaction can be carried namely non-anhydrous solvents and in air. Publications: (1) Gallop, C. W. D.; Bobin, M.; Hourani, P.; Dwyer, J.; Roe, S. M.; Viseux, E. M. E. J. Org. Chem. 2013, 6522–6528. (2) Gallop, C. W. D.; Zinser, C.; Guest, D.; Navarro, O. Synlett 2014, 2225–2228. (3) Gallop, C. W. D.; Chen, M.-T.; Navarro, O. Org. Lett 2014, 3724–3727.

For the preparation of semiconducting polymers often ‘standard’ catalytic systems are used without further optimisation. New ligands, such as N-heterocyclic carbenes have shown excellent activity in cross-coupling reactions (e.g. Suzuki-Miyaura reaction, or Hartwig-Buchwald amination). These systems show excellent conversions under mild conditions and even allow the use of aryl chlorides as reagents. Nevertheless, previously no system has been reported for the synthesis of conjugated polymers, e.g. the Suzuki polycondensation or Buchwald-Hartwig type polycondensation using these catalysts. A NHC-Pd based catalytic system was optimised for a polyamination reaction and the catalyst [(IPr)Pd(allyl)Cl] was found to be the most active. Polytriarylamines were synthesised using the optimised catalytic system and tested in organic field-effect transistors. Mobilities found were low which was found to be attributed to the presence of high molecular weight fractions. Molecular weights were controlled using an in situ end-capping approach and polymers tested in the semiconducting layer of OFETs gave similar mobilities tothose reported earlier. Several polytriarylamines, which have not been reported previously, were synthesised using NHC-chemistry and the in situ end-cappingapproach, as well as polytriarylamines that have been reported previously using Pd/phosphine catalysts. One library containing polymers based on biphenyles andbridged biphenyles and another library containing polymers with bridged oligoarenes were synthesised. Suzuki polycondensation was also studied besides the polyamination protocol and low catalyst loadings and reaction temperatures could be realised using a NHC-Pd catalyst. Sulfur containing monomers that could not be polymerised using the polyamination were polymerised successfully. All polymers were fully characterised and studied as the active layer in organic field-effect transistors. The highest mobilities determined for these polymers (~10-2 cm2/Vs) is close to the highest reported for this class of polymer reported to date.

The oxidative addition products trans-[Pd(NHC)2(Ar)Cl] (NHC = cyclo-C{N`BuCH}2; Ar = Me-4-C6H4, MeO-4-C6H4, CO2Me-4-C6H4) have been isolated in good yields from the reactions of ArCI with the amination precatalyst [Pd(NHC)2] and structurally characterized. The former undergo reversible dissociation of one NHC ligand at elevated temperatures, and a value of 25.57 kcal mol-1 has been determined for the Pd- NHC bond dissociation enthalpy in the case where Ar = Me-4-C6H4. Detailed kinetic studies (via extensive NMR studies) have established that the oxidative addition reactions proceed by a dissociative mechanism. Rate data for the oxidative addition of Me-4-C6H4Cl to [Pd(NHC)2] compared to that obtained for the [Pd(NHC)2}-catalysed coupling of morpholine with 4-chlorotoluene are consistent with a rate-determining oxidative addition in the catalytic amination reaction. The relative rates of oxidative addition of the three aryl chlorides to [Pd(NHC)21(CO2Me-4-C6H4C1> Me-4-C6H4C1> MeO-4-C6H4C1) reflect the electronic nature of the substituents and also parallel observed trends in the coupling efficiency for these aryl halides in aminations. Transmetallations tudies resulted in the isolation and structural characteristaiono f palladacycle [Pd(cyclo-C{N`BuCH}2)(μ-O(2-CH2C6H4))]2 from the reaction of [Pd(NHC)2] with 2-chlorobenzylalcohol. Attempts to isolate and fully characterise [Pd(cyclo-C{N'BuCH}2)(μ-O(2-CH2CH2C6H4))]2 and the amine analogue [Pd(cyclo- C {N`BuCH}2)(μ-NH(2-CH2C6H4))]2 were unsuccessful. Attempts to prepare [Ni(cyclo-C{NtBuCH}Z)] by a conventional route led to the formation of several unexpected Ni-NHC complexes. The reaction between [Ni(1,5- COD)2] and 1,3-bis-tert-butylimidazol-2-ylidene in the presence of silicone grease affords the siloxane bridged dimer [Ni(cyclo-C{N`BuCH}2)(O{Me2SiOSiMe2}-it- 0)]2. Using greaseless apparatus, the same reaction yields the Ni-Ni dimer [Ni(cyclo-C{N`BuCH}2)( -(cyclo-C{N`BuCH} {NCH}))]2, via two structurally characterised intermediates V

Chapter 1: Gives the reader a background on carbenes paying particular attention to N-heterocyclic carbenes (NHCs). The chapter describes NHC's electronic and structural properties and their behaviour as ligands. The recent usage of NHC-palladium complexes as catalysts for cross-coupling reactions is explored. Chapter 2: Provides a background on NHC-palladium complexes bearing N-donors as throwaway ligands, highlighting the importance of throw-away ligands on catalytic activity. The chapter describes the preparation of a number of novel NHC-palladium complexes bearing throw-away ligands and the activity of (IPr*)PdCl2(TEA) in Buchwald-Hartwig aminations is explored. Chapter 3: Provides a background on the Mizoroki Heck reaction, focusing on the importance of charged intermediates in the process. Then reviews the current development of anionic NHC-palladium complexes in the literature. An account of the discovery and preparation of novel [(NHC)PdCl3[TBA] complexes and the catalytic activity of [(SIPr)PdCl3[TBA] in Mizoroki-Heck coupling reactions is given. A plausible Amotore-Jutand type mechanism is proposed which is supported by DFT calculations provided by research collaborators. Chapter 4: Provides a background on C-H activation reactions catalysed by palladium compounds with particular focus on acetoxylation reactions. The chapter describes the synthesis of [(NHC)PdCl2X][Y] complexes including the development of [(IMes)PdCl2OAc][TBA] and its performance in acetoxylation reactions. A proposed mechanism for the reaction of [(IMes)PdCl2OAc][TBA] is discussed, using experimental observations.

The syntheses and characterization of a series of (NHC)Pd(II) complexes (NHC = N-heterocyclic carbene) are described. A variety of architectures and precursors have been employed to lead to numerous air- and moisture-stable complexes. The use of those complexes as pre-catalysts in cross-coupling (Suzuki- Miyaura, Buchwald-Hartwig) and related (catalytic dehalogenation, £-ketone arylation) reactions is also discussed. A comparison of the activity of a variety of (NHC)Pd complexes as pre-catalysts for cross-coupling reactions was carried out. The results indicate that the activation of those pre-catalysts, leading to the catalytically active [(NHC)Pd(0)] species, was key in assuring high catalytic performance under mild reaction conditions. For the first series of complexes described, (NHC)Pd(allyl)Cl complexes, a better understanding of the process leading to the catalytically active species has permitted us to introduce simple modifications (alkyl or aryl groups at the allyl moiety) that dramatically alter the performance of the complexes by facilitating their activation, decreasing reaction times, catalyst loadings and even allowing reactions to be conducted at room temperature. Catalyst loadings as low as 0.05 mol% can be used for the Suzuki-Miyaura crosscoupling of aryl chlorides and aryl boronic acids at room temperature, leading to the synthesis of poly-ortho-substituted biaryls in excellent yields. This catalyst loading is the lowest ever used for this purpose. The system also allows for the first examples of coupling between aryl chlorides and alkenyl boronic acids at room temperature. When the temperature is raised to 80 ¢ XC for these reactions, a catalyst loading as low as 50 ppm can be used to effectively carry out Suzuki-Miyaura cross-couplings in remarkably short reaction times. As an added advantage, these complexes are air- and moisture-stable and can be prepared in a facile one-pot, multigram scale synthesis from commercially available starting materials in very high yields. The second series of complexes described revolves around the (NHC)Pd(acac)n framework. These complexes are also air- and moisture-stable and can be prepared in a one-step synthesis in high yields from commercially available materials. These complexes were tested forƒn £-ketone arylation and Buchwald-Hartwig amination reactions affording high yields of the desired products, in short reaction times and mild reaction conditions.

Despite the appearance in the market of platinum compounds with minor side effects than cisplatin (i.e. carboplatin and oxaliplatin), they did not solve the ineffectiveness on some types of tumors, having the same mechanism of action proposed for cisplatin (DNA platination). For this reason, many research groups have focused their attention on the synthesis and determination of the anticancer properties of compounds with metals different from platinum. Among the most investigated metals there are certainly ruthenium and gold and, only recently, palladium. The latter, despite belonging to the same group of platinum, has some rather different features: •Better water solubility of its complexes. •Structure-activity relationships and mechanisms of action generally different from platinum compounds. However, the fast dissociation pattern of palladium complexes compared to platinum represents a problem since the speciation, which heavily affects the biological activity and the pharmacokinetic properties, could be increased. To remedy this contraindication the most direct option is the introduction of ligands firmly anchored to the metal such as N-Heterocylic Carbenes (NHCs), which are known to give strong s-bonds with most of the transition metals. Moreover, several NHC-palladium complexes have already exhibited an interesting cytotoxic activity in vitro and tumour growth suppression even in vivo. In this PhD thesis, the synthesis and characterization of new palladium compounds stabilized by different types of N-Heterocyclic Carbenes and important organometallic fragments such as h3-allyl-Pd(II), palladacyclopentadienyl and h2-olefin-Pd(0) will be exposed. The reactivity and the importance in many catalytic processes of the fragments reported in Fig. A1 are well known, on the contrary, their biological activity is almost unexplored. Starting from these premises, it was decided to test the synthesized compounds toward different tumor lines, particularly on ovarian carcinoma, and human fibroblasts (healthy cells). From the antiproliferative activity data collected for about one hundred compounds, emerges that, regardless of the nature of the selected carbene ligand, the most active compounds bear the allyl fragment. For these species the evaluation of their activity in vivo and experiments aimed at identify the primary biological target, in order to propose the possible mechanism of action, are planned. A class of compounds generally slightly less active than that containing the allyl residue is represented by the palladacyclopentadienyl complexes and their derivatives. Nevertheless, for some of the synthesized compounds, an excellent antiproliferative and proapoptotic activity has been shown on ovarian cancer cell lines (CisPt sensitive and CisPt resistance), accompanied by a poor activity against normal cells. For the compound 40a a thorough investigation on the main biological target, which was found to be DNA, and on the degree of uptake in tumor cells was also carried out. Due to the high stability imparted by the palladaciclopentadienyl fragment and the chelatig biscarbene ligand, this compound does not undergo substitution reactions when reacted with reduced glutathione (GSH), which is a potential coordinating species present in abundance in the biological environment. It is therefore reasonable to suppose that the interaction with the DNA occurs through non-covalent interactions with the polynucleotide chain. Finally, the class of compounds decidedly less active than those described so far is represented by the Pd (0) derivatives stabilized by olefinic ligands. For these complexes the antiproliferative and proapoptotic activity was evaluated only in ovarian carcinoma lines, observing only in very few cases IC50 values comparable to those of cisplatin.

Lo scopo del seguente lavoro di tesi è la sintesi e lo studio di nuovi leganti chirali N-eterociclici ad anello espanso derivanti dal diacido canforico. Lo sviluppo di nuovi leganti chirali nasce dalla possibilità di utilizzo in catalisi enantioselettiva. Questa tipologia di leganti sono facilmente sintetizzati dal diacido canforico utilizzando diverse vie di sintesi. La via di sintesi utilizzata permette di ottenere facilmente una funzionalizzazione asimmetrica. Il legante è stato studiato nella sintesi di un nuovo complesso chirale di Pd(II) utilizzando diverse condizioni di reazione. Inoltre, sono state studiate numerose vie di sintesi per nuovi leganti utilizzando i precursori dei leganti e due diversi epossidi. The aim of my training period has been the synthesis of new chiral N-heterocyclic carbene precursors starting from camphoric acid. The development of new chiral ligands starts from their possible use in new catalytic systems for enantioselective transformations. These kinds of ligands are easily synthetized from camphoric acid following different strategies. The synthetic pathway used makes simple the asymmetric functionalization. The ligand was employed in the synthesis of a new complex of Pd(II) in different conditions. In addition, numerous synthetic pathways have been investigated for new ligands using their precursors and two different epoxides.

A bifunctional imidazolium linker was used for the production of highly crosslinked element organic frameworks by Suzuki-coupling with tetrafunctional boronic acids. The resulting porous materials are good heterogeneous organocatalysts in the N-heterocyclic carbene-catalyzed conjugated umpolung of α,β-unsaturated cinnamaldehyde
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

A bifunctional imidazolium linker was used for the production of highly crosslinked element organic frameworks by Suzuki-coupling with tetrafunctional boronic acids. The resulting porous materials are good heterogeneous organocatalysts in the N-heterocyclic carbene-catalyzed conjugated umpolung of α,β-unsaturated cinnamaldehyde.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

La present tesi doctoral està adreçada al desenvolupament de catalitzadors que permetin dur a terme processos sintètics de manera més eficient i sostenible. Es presenten dues noves famílies de catalitzadors suportats, ambdues pertanyents al grup de complexos organometàl·lics moleculars immobilitzats sobre un suport sòlid. La primera família inclou complexos de Pd amb lligands carbè N-heterocíclic monodentats de gran impediment estèric, immobilitzats sobre òxids inorgànics, com ara sílicas, alúmina o òxid de titani. Aquesta família de catalitzadors es va aplicar en dos tipus de reaccions: i) reaccions d'acoblament C-C i ii) semireducción d'alquins. Entre les reaccions d'acoblament esmentades, els complexos de [Pd (NHC)] immobilitzats es van aplicar a les reaccions de Suzuki, Heck i Sonogashira, i es van avaluar en base a la seva activitat, selectivitat i reciclabilitat. A més, en el cas de les reaccions de Suzuki i Sonogashira, aquests catalitzadors també es van aplicar en condicions de flux continu. L'aplicació d'aquesta família de catalitzadors en la semireducció selectiva d'alquins es va dur a terme utilitzant dues metodologies diferents: utilitzant hidrogen molecular, o bé utilitzant el sistema trietilamina / àcid fòrmic com donador de H (condicions de transferència d'hidrogen). La segona família de catalitzadors suportats contempla complexos de Rh (I) estabilitzats amb lligands bidentats de tipus carbé N-heterocíclic, amb quiralitat axial, i funcionalitzats amb un grup piré. La immobilització d'aquests complexos de Rh sobre la superfície de nanotubs de carboni "multi-walled" va tenir lloc mitjançant interaccions de tipus "pi-pi stacking" entre la superfície dels nanotubs i el grup piré present en el lligand. Finalment, es presenten els resultats obtinguts en l'aplicació d'aquests complexos de Rh en diversos processos catalítics.
La presente tesis doctoral se centra en el desarrollo de catalizadores que permitan llevar a cabo procesos sintéticos de manera más eficiente y sostenible. Se presentan dos nuevas familias de catalizadores soportados, ambas pertenecientes al grupo de complejos organometálicos moleculares inmovilizados sobre un soporte sólido. La primera familia incluye complejos de Pd con ligandos carbeno N-heterocíclico monodentados de gran impedimento estérico, inmovilizados sobre óxidos inorgánicos, como sílicas, alúmina u òxido de titanio. Esta familia de catalizadores se aplicó en dos tipos de reacciones: i) reacciones de acoplamiento C-C y ii) semireducción de alquinos. Entre las reacciones de acoplamiento mencionadas, los complejos de [Pd(NHC)] inmovilizados se aplicaron en las reacciones de Suzuki, Heck y Sonogashira, y se evaluaron en base a su actividad, selectividad y reciclabilidad. Además, en el caso de las reacciones de Suzuki y Sonogashira, estos catalizadores también se aplicaron en condiciones de flujo continuo. La aplicación de esta familia de catalizadores en la semireducción selectiva de alquinos se llevó a cabo utilizando dos metodologías diferentes: utilizando hidrógeno molecular, o bien utilizando el sistema trietilamina/ácido fórmico como dador de H (condiciones de transferencia de hidrógeno). La segunda familia de catalizadores soportados contempla complejos de Rh(I) estabilizados con ligandos bidentados de tipo carbeno N-heterocíclico, con quiralidad axial, y funcionalizados con un grupo pireno. La inmovilización de estos complejos de Rh sobre la superficie de nanotubos de carbono "multi-walled" tuvo lugar mediante interacciones de tipo "pi-pi stacking" entre la superficie de los nanotubos y el grupo pireno presente en el ligando. Finalmente, se presentan los resultados obtenidos en la aplicación de estos complejos de Rh en varios procesos catalíticos.
The present PhD thesis aims at contributing to the development of more efficient and sustainable synthetic processes through catalysis. In this regard, two families of new solid-supported catalysts are presented. Both families belong to the group of molecularly defined organometallic complexes immobilized onto a solid support. The first family includes Pd complexes of sterically hindered monodentate N-Heterocylic Carbene ligands supported onto inorganic oxide materials, namely silicas, alumina and titania. This family of catalysts was applied in two types of reactions: i) C-C cross-couplings and ii) semireduction of alkynes. Among cross-coupling reactions, the supported [Pd(NHC)] complexes could be applied in Suzuki, Heck and Sonogashira couplings and their performance was assessed in terms of activity, selectivity and reusability. For the Suzuki and Sonogashira couplings, the catalysts were also appied under continuous flow conditions. The application of this family of catalysts in the selective reduction of alkynes was carried out following two different methodologies: using hydrogen gas, or using triethylamine/formic acid as the H-donor system (transfer hydrogenation conditions). The second family of solid-supported catalysts features Rh(I) complexes bearing axially chiral bidentate N-Heterocyclic carbene ligands functionalized with a pyrene moiety. Immobilization of these Rh complexes onto the surface of multi-walled carbon nanotubes was achieved by means of "pi-pi stacking interactions" between the surface of the nanotubes and the pyrene moiety present in the ligand. Results obtained from the application of these complexes as catalysts in various reactions are presented.

This thesis describes the synthesis and isolation of silver, mercury, ruthenium and palladium complexes of bidentate N-heterocyclic carbenes (NHCs), derived from imidazolium-linked cyclophanes and related bis-imidazolium salts. The cyclophane structures contain two imidazolyl links between ortho- and meta- substituted aromatic rings and the related structures are ortho-, meta- and para-xylyl linked bis-imidazolium salts. The complexes have been characterised by NMR spectroscopy and X-ray crystallography. The synthesis of five new silver complexes has been achieved via a simple complexation reaction of the cyclophane and bis-imidazolium salts with the basic metal source Ag2O. The new silver carbene systems are thermally stable. Three of the complexes are dinuclear, cationic complexes, while two are mononuclear complexes, one cationic and one neutral. A number of mono- and di-nuclear mercury(II)-NHC complexes have been synthesised from the ortho- and meta-linked cyclophanes and the related meta-linked bis-imidazolium salts. The mercury complexes were prepared by direct mercuration method using mercury(II) acetate. The syntheses were perfomed in air and the complexes are stable to air and moisture. Mercury complexes I and II represent the first example of mononuclear metal complexes derived from meta-substituted imidazolium-linked cyclophanes. NHC-ligand transfer reactions from NHC-silver complexes and NHC-mercury complexes are described. An ortho-cyclophane ligand was successfully transfered from a silver complex to its palladium counterpart. Furthermore, palladium complex III, bearing a para-xylyl linked bis-NHC ligand, was made by transmetallation from both a silver and mercury complex. This is the first reported NHC-palladium complex of a para-xylyl linked bis-NHC ligand. A new redox transmetallation method for NHC ligand transfer, using a mercury complex, is presented. A palladium complex was made via redox transmetallation using a mercury complex of an ortho-NHC-cyclophane. A ruthenium(II)-NHC complex, IV containing an ortho-cyclophane ligand has been prepared via silver transmetallation and in situ complexation methods. In the transmetallation route, a silver complex of an ortho-cyclophane was treated with RuCl2(PPh3)3 to form IV. This complex represents the first example of a ruthenium complex bearing an NHC-cyclophane ligand, v and is also the first example of a metal complex derived from an imidazolium-linked cyclophane where the arene unit of the cyclophane is also involved in bonding to the metal centre.

This thesis is concerned with the synthesis of two di-N-heterocyclic carbene ligands, and their reactivity towards nickel and palladium precursors in order to synthesise new organometallic pre-catalysts for a number of important reactions. The catalytic properties of a new rhodium C₆₀ compound are also investigated, with relevance to the evaluation of C₆₀ as a hydrogen storage medium. Chapter 1 reviews the preparation and chemistry of N-heterocyclic carbenes, emphasising their organometallic reactivity and role as ancillary ligands in homogeneous transition metal catalysis. An overview of relevant nickel and palladium catalysis is also presented, including olefin polymerisation, olefm / CO copolymerisation and Heck coupling reactions. Chapter 2 describes the synthesis and characterisation of the dicarbene ligands ^tBuCC^meth and ^tBuCC^eth and their reactions with various nickel precursors in attempts to prepare chelating dicarbene nickel cis-dihalide complexes. The synthesis, characterisation and chemical reactivity of the cations [Ni(^tBuCC^meth)₂]²⁺, [(^tBuCC^meth)NiCl(PMe₃)] ⁺ and [(^tBuCC^eth)NiCl(PMe₃)]⁺ is detailed, and their X-ray structures are compared. The unsuccessful preparation of [Ni(^tBuCC^eth)₂] ²⁺ and the relative stability of the monocations with respect to dicarbene substitution is discussed and attributed to steric factors. Chapter 3 describes the synthesis, characterisation, reactivity and catalytic studies of simple nickel and palladium cis-dimethyl complexes of the chelating dicarbene ligands. Variable temperature ¹H NMR spectroscopy showed contrasting rates of thermal hydrocarbon elimination from Ni(^tBuCC^meth)Me₂ and Ni(^tBuCC^eth)Me₂, which has previously been observed for chelating bis-phosphine analogues with various P,P' linkages (CH₂)_n . These observations further corroborate the analogy between dicarbene and 6/s-phosphine ligands. It was demonstrated that the compounds Pd(^tBuCC^meth)Me₂and Pd(^tBuCC^eth)Me₂ are effective pre-catalysts for the Heck coupling of 4-bromoanisole and n-butyl acrylate. In addition cations of the type [(^tBuCC^meth/eth)PdMe(L)]⁺ (L = pyridine, THF) which are relevant to olefin / CO copolymerisation were prepared. The X-ray structures of M(^tBuCC^eth)Me2 (M = Ni, Pd) are discussed as well as the synthesis and structural characterisation of [(|Li-tBu CC meth){Ni(PMe₃)Me₂}₂]. Chapter 4 presents a brief introduction to some relevant C₆₀ chemistry and to the concept of hydrogen storage. The synthesis and characterisation of a new rhodium Ceo compound is described. The compound catalysed the hydrogenation and hydroformylation of simple alkenes as well as the hydrogenation of C₆₀ to C₆₀H₃₆ . The recovery of hydrogen gas from C₆₀H₃₆ was investigated in order to evaluate C₆₀ as a hydrogen storage medium. Chapter 5 outlines the experimental details for the synthesis, characterisation, reactions and catalytic studies of the new compounds described in the preceding three chapters. Chapter 6 presents the characterising data for the new compounds described in chapters 2 and 3. Appendices contain details of the crystallographic data for the eight structurally characterised compounds described in chapters 2 and 3.

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.

Several studies have been carried out to establish the sequence of intermediates in the catalytic cycle for amination of aryl halides. I ,2 The mechanism suggested by Cloke and Caddick group for the catalytic amination of aryl chloride employing [Pd(NRC)2l as precatalyst (NRC = ·N-heterocyclic carbene), proposed a neutral, 12-electrons mono-ligated Pd(NHC) species as the active intermediate.3 The isolation of a series of (ItBu)2Pd(R-aryl)chloride complexes (ltBu = 1,3-di-tert-butylimidazol-2-ylidene) allowed for kinetic studies hence leading to a mechanistic understanding of the I oxidative addition step, confirming that it occurs by a dissociative mechanism. The subsequent step in the amination catalytic cycle, namely, the dissociation of a carbene and coordination of an amine was investigated and the results are presented in this thesis, and an array of (ItBu)Pd(amine)(R-aryl)chloride complexes were isolated and fully characterized. Kinetic studies were undertaken in order to identify the rate determinig step of the transamination reaction. Moreover, the electronic properties of the para-substituents (R) on the aryl groups of the (ItBu)2Pd(R-aryl)chloride complexes were found not only to influence the rate of the oxidative addition reaction, but also to affect the carbene displacement by the amines. Parallel research based on the understanding of the mechanism of oxidative addition of alkyl halides to the Pd(NHC)2 species have been undertaken, and the synthesis of (ItBu)Pd(neopentyl)chloride (trans isomer) and (IPr)Pd(neopentyl)chloride (cis isomer) (IPr = 1,3-Bis(2,6-Diisopropylphenyl)imidazol-2-ylidene) were. accomplished. Reactivity of these· two complexes was tested toward amines, revealing the significant influence ofN-substituents on the stability of the resulting compounds, and highlighting a possible barrier concerning the achievement of a Pd-catalysed alkyl amination reaction. The oxidative addition of (trimethylsilyl)methyl iodide to Pd(ItBu)z complex was investigated for comparison to the oxidative addition reactions of alkyl halides to the same palladium complex. The unexpected resultant complex, Pd(CHzltBu)zlz, was subjected to DFT study by Dr. Hazari to confirm the zwitterionic nature of the ligand. Kinetic study was conducted on the oxidative addition of TMSI to Pd(ItBu)z to reveal the occurrence of pre-dissociation of one ligand before the addition ofTMSI to yield the [(ItBu)Pd(TMS)(J.t-I)]z.

The focus of this thesis is the synthesis of novel palladium(0) complexes bearing the ligand 1,3,4,5-tetramethylimidazol-2-ylidene (ITMe), a small percentage buried volume N-heterocyclic carbene. These complexes have been assessed as mediators for the 1,2-additions of hetero element-element bonds to unsaturated organic moieties. In particular, Si-Si, Si-B and B-B bond additions to alkynes and azobenzenes were chosen as reactions of interest due to their challenging nature. Chapter 1 introduces the concept of transition metal mediated element-element additions to alkynes and includes a thorough review on the current literature state. Chapter 2 describes the first solution based synthesis of [Pd(ITMe)2] and its in situ reactivity with Me3SiSiMe3 under mild conditions to form the novel complex cis-[Pd(ITMe)2(SiMe3)2], the first NHC-bearing complex resulting from the oxidative addition of hexamethyldisilane to a palladium centre. The use of this complex as a pre-catalyst for the bis(silyl)ation of electronically and sterically challenging internal acetylenes using non-activated disilanes is reported. A series of novel 1,2-disilylstilbenes were synthesized in high yield and with 100% Z-stereoselectivity. Chapter 3 details the use of [Pd(ITMe)2(PhC≡CPh)], the first bis(N-heterocyclic carbene)Pd(0)-alkyne complex, as a highly reactive pre-catalyst in the silaboration of terminal and internal alkynes to yield a number of known and novel 1-silyl-2-boryl alkenes. Unprecedented mild reaction temperatures for terminal alkynes, short reaction times and low catalytic loadings are reported. During mechanistic studies, cis-[Pd(ITMe)2(SiMe2Ph)(Bpin)] was directly synthesized by oxidative addition of PhMe2SiBpin to [Pd(ITMe)2(PhC≡CPh)]. This represents a very rare example of a (silyl)(boryl)palladium complex. A plausible catalyst decomposition route was also examined. In Chapter 4, [Pd(ITMe)2(PhC≡CPh)] acts as a highly reactive pre-catalyst in the unprecedented homogeneous catalyzed diboration of terminal and internal alkynes, yielding a number of novel and known syn-1,2-diborylalkenes in a 100% stereoselective manner. DFT calculations conducted by our collaborators suggest that a similar reaction pathway to that proposed for platinum phosphine analogues is followed, and that destabilization of key intermediates by ITMe is vital to the overall success for the palladium-catalyzed B-B addition to alkynes. Chapter 5 reports the use of [Pd(ITMe)2(PhC≡CPh)] as a highly active pre-catalyst in the diboration and silaboration of azobenzenes to synthesize a series of novel functionalized hydrazines. The reactions proceed using commercially available diboranes and silaboranes under mild reaction conditions. Preliminary investigations into further reactivity of [Pd(ITMe)2(PhC≡CPh)], [Pd(ITMe)2] and cis-[Pd(ITMe)2(SiR3)2] (SiR3 = SiMe2Ph or SiMe3) are reported in Chapter 6. This includes the oxidative cleavage of Me3GeGeMe3 by [Pd(ITMe)2(PhC≡CPh)] to form the novel cis-[Pd(ITMe)2(GeMe3)2] and an initial study into the catalytic alkyne digermylations. The hydrogenation of diphenylacetylene to form Z-stilbene using an amine-borane and catalytic quantities of [Pd(ITMe)2(PhC≡CPh)] was also investigated. Finally, the stoichiometric reactions of allyl bromides with cis-[Pd(ITMe)2(SiR3)2] to form the novel complexes trans-[Pd(ITMe)2(SiR3)(Br)] are detailed.

This thesis describes the synthesis of coordinatively unsaturated bis- and mono-N-heterocyclic carbenes of Group 10 metal(0) complexes (Ni, Pd, Pt) and the study of their reaction chemistry and catalytic behaviour. Novel coordinatively unsaturated mono-NHC-Pd0 (NHC = N-heterocyclic carbene) complexes stabilised with activated olefin ligands (dimethylfumarate, DMFU and p-benzoquinone, BQ) have been synthesised and characterised, including by X-ray crystallography. The Pd (NHC)(DMFU)2 complexes were found to be the thermodynamic products of an equilibrium between bis- and mono-NHC-Pd (DMFU) species, the equilibrium reaction driven by the formation of an NHC-DMFU coupling product. The Pt (NHC)(DMFU)2 complex was also synthesised. Novel coordinatively unsaturated bis- and mono-NHC-Ni complexes stabilised with DMFU ligands were synthesised and crystallographically characterised. These Ni complexes have a dynamic behaviour in solution, and the same equilibrium observed for palladium between bis- and mono-NHC-M (DMFU) species with formation of an NHC-DMFU coupling product was also demonstrated to occur with nickel. Possible mechanisms for this unusual NHC-DMFU coupling process at these nickel and palladium(O) centres are discussed. The coordinatively unsaturated mono-NHC-Pd (DMFU/BQ) complexes, as well a bis-NHC-Pd complex, were tested as precatalysts in the telomerization of butadiene with methanol. All of these well-defined complexes were found to be extremely active and selective catalysts in the telomerization reaction. The C-H oxidative addition of imidazolium salts/ionic liquids to a coordinatively unsaturated mono-NHC-Pt0 complex and bis-NHC-Ni /Pd complexes was studied. These oxidative addition processes occur quickly under mild conditions and produce the corresponding bis- or tris-NHC-Mn-H complexes as surprisingly stable compounds. X-Ray crystallographic studies of the two tris-NHC-Mn-hydrido complexes (M= Ni, Pd) with the hydride ligands located are reported The combination of the imidazolium C2-H oxidative addition and the NHC-hydrocarbyl reductive elimination processes into a catalytic cycle to form a unique Ni-catalysed imidazo lium-alkene coupling reaction is reported. The scope of this new catalytic transformation that produces 2-alkylimidazolium salts under mild conditions is extended to other types of azolium salts. The implications of these results for NHC chemistry and for the use of imidazo Hum-based ionic liquids as solvents in transition-metal catalysed reactions is discussed.

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.

In the last ten years, N-heterocyclic carbenes(NHCs) have gained tremendous
popularity, notably as highly versatile ligands for transition metals. Their strong -donating
properties, associated with high steric hindrance, often impart enhanced stability and activity to a given metallic center. Two main successes of the NHCs in homogeneous catalysis are arguably the ruthenium-mediated olefin metathesis and the palladium-promoted crosscoupling reactions.In this work, we have studied the effect of N-heterocyclic carbenes as supporting ligands in well-defined complexes of palladium(II), gallium(III), and gold(I) that we used in homogeneous catalysis.Notably, we have synthesized, in very straightforward manners, two families of palladium compounds of formulae [(NHC)Pd(L)Cl], where L, which is a R-allyl or R-acac moiety, acts as a protecting shell for the catalytically active [(NHC)Pd0] species. Hence,
upon activation under the reaction conditions, these new Pd complexes were found extremely active in the Suzuki-Miyaura, the Buchwald-Hartwig, and the -ketone arylation cross-coupling reactions. More precisely, the more active "R-allyl family" allowed for reactions to be performed with as low as 10 ppm of palladium.
A series of [(NHC)GaCl3] complexes wa synthesized via a simple one-step procedure. The resulting unprecedented NHC-GaIII compounds were found extremely stable but showed only moderate activity in isomerization reactions.Demonstrating further the versatile application of NHCs in metal-based catalysis, we
developed several new catalytic transformations using [(NHC)AuCl] complexes. Hence,these pre-catalysts, activated in situ with a silver salt, proved to be excellent activators of
alkynes, allenes, and alkenes. This led to the development of efficient synthetically useful
protocols, encompassing enyne cycloisomerization, indene cyclization,formation of conjugated enone, and allylic rearrangement.
KEYWORDS gallium - gold - homogeneous catalysis - N-heterocyclic carbene - palladium 8
En los últimos diez años, los carbenos N-heterocíclicos (NHCs) han ganado una gran
popularidad, especialmente como ligandos versátiles de metales de transición. Su fuerte
carácter −donor, asociado con su gran impedimento estérico, confieren a menudo una
mayor estabilidad y actividad al centro metálico en cuestión. Los dos mayores éxitos de los
NHCs en catálisis homogénea se encuentran, sin duda, en la metátesis de olefinas catalizada
por rutenio y en las reacciones de acoplamiento cruzado promovidas por paladio.
En este trabajo, hemos estudiado el efecto de los carbenos N-heterocíclicos como
ligandos en complejos bien definidos de paladio(II), galio(III) y oro(I), que hemos empleado
en catálisis homogénea.En particular, hemos sintetizado, de forma directa, dos familias de compuestos de paladio de fórmula general [(NHC)Pd(L)Cl] donde L, grupo R-alilo o R-acac, actúa como protector para las especies catalíticamente activas [(NHC)Pd0]. De hecho, tras la activación
en las condiciones de reacción, estos nuevos complejos de paladio se mostraron extremadamente activos en las reacciones de Suzuki-Miyaura, de Buchwald-Hartwig y en la -arilación de cetonas. Más concretamente, la 'familia R-arilo', más activa, permitió llevar a cabo estas reacciones con tan sólo 10 ppm de paladio.Una serie de complejos [(NHC)GaCl3] fue preparada en una simple etapa. Los compuestos resultantes NHC-GaIII, sin precedentes en la literatura, se mostraron extremadamente estables pero sólo moderadamente activos en reacciones de isomerización.Con el fin seguir ampliando la gran aplicabilidad de los NHCs en catálisis con
metales, estudiamos varias nueva transformaciones utilizando los complejos [(NHC)AuCl].De hecho, estos pre-catalizadores, activados in situ con una sal de plata, demostraron ser excelente activadores de alquinos, alenos y alquenos. Esto llevó al desarrollo de protocolos eficientes, y sintéticamente útiles, tales como la cicloisomerización de eninos, la ciclación de
indenos, la formación de enonas conjugadas, y reordenamientos arílicos.

Thesis (Master)--İzmir Institute of Technology, İzmir, 2005.
Keywords: Palladium, Immobilization, Heck Reaction, Palladium-N-Heterocyclic Carbene, Carbon-Carbon Coupling. Includes bibliographical references (leaves. 89-104).

N-Heterocyclic carbenes (NHCs) have emerged as appropriate replacements for phosphines in transition metal catalyzed cross-coupling chemistry. The advantages of NHCs over phosphines include ease of handling, minimal toxicity, stability and powerful electron donating properties. Improvement of catalytic processes has become increasingly relevant in light of prospective applications of organic transformations in industry as well as in synthetic laboratories. To that end, NHCs represent an important class of catalysts and catalyst modifiers which mandate continued research efforts. Prospective applications of processes catalyzed by NHCs and NHC-metal catalysts provide a strong impetus to develop them and related methodologies. This dissertation focuses on the development of NHCs and NHC ligated metal complexes in various catalytic transformations. NHC ligated palladium catalysts were synthesized in simplified protocols amenable to large-scale industrial applications. The catalysts were utilized in developing different valuable coupling methodologies. Significant advances were achieved in Suzuki-Miyaura, á-arylation of ketones and Kumada-Tamao-Corriu cross coupling reactions. The focus of the work was to make the synthesized catalysts and their activity in these methodologies acceptable to wider range of applications. The strongly nucleophilic nature and easily tunable steric and electronic properties of NHCs have been exploited to mediate organic transformations by utilizing NHCs as catalysts. The metal-free catalysis has an added advantage of being more environmentally friendly. NHCs have proven to be excellent transesterification catalysts for reactions of alcohol and esters. An efficient catalytic system, widening the scope of N-heterocyclic carbenes catalyzed transesterification/acylation reaction of alcohols is described. The methodology has been expanded to include secondary alcohols as well as phosphorus based esters.

L’objectif de cette thèse portait sur la synthèse de complexes portant un ligand NHC associé à une fonction oxygénée et à leur application en catalyse d’oligomérisation de l’éthylène. Dans le but de synthétiser des complexes avec des ligands NHCalcool, les complexes d’argent correspondants ont été synthétisés et utilisés en transmétallation. Aucun résultat concluant n’a pu être obtenu avec le nickel à cause de l’acidité du proton alcoolique. Mais un ligand NHC-alcoolate a pu être obtenu par déprotonation directe du pro-ligand avec une base forte. Il fut alors possible d’accéder à des complexes de nickel polynucléaires, certains incorporant dans leur structure des cations lithium provenant de la base utilisée. Par comparaison, des complexes de palladium ont été synthétisés avec des NHCs-alcool ou -alcoolate par réaction des pro-ligands avec Pd(acac)2 suivie de réactions acido-basiques. Etant donné la difficulté d’obtention des complexes de nickel avec des ligands NHC-alcool, la fonction éther a été étudiée. Les complexes résultants ont été testés en oligomérisation de l’éthylène
The purpose of this work was the synthesis of complexes bearing O-functionalized NHC ligands in order to test their catalytic properties in ethylene oligomerization. In order to have access to alcohol-functionalized complexes, the corresponding silver complexes were synthesized for transmetallation purpose. Whereas no concluding results were obtained with the alcohol function in association with nickel, it was possible to access an alcoholate-functionalized NHC ligand by deprotonation of the corresponding pro-ligand. Thus, polynuclear nickel complexes were prepared, some of them included in their structure a lithium cation originating from the base. For comparison, alcohol- and alcoholate-functionalized NHC palladium complexes were synthesized by direct reaction of the pro-ligand with Pd(acac)2 followed by acidobasic reactions. Because of the complexity of the chemistry of NHC-alcohol ligands associated with nickel, the ether functionality was explored. A library of nickel complexes was synthesized and tested in the catalytic ethylene oligomerization

Cette thèse apporte une contribution au développement de complexes carbènes N-hétérocycliques-palladium basés sur des calix[4]arènes: leur synthèse, leur caractérisation ainsi que l'évaluation de leur activité catalytique est presenté. Pour cela, un calix[4]arène mono-substitué a été préparé conformément aux procédures classiques, puis les précurseurs de nouveaux ligands NHC ont été obtenus. Subissant l'alkylation avec du n-butylbromide et puis une métallation subséquente avec du palladium et de la pyridine, quatorze nouveaux complexes ont été obtenus. Après les caractérisations complètes en solution et à l'état solide, l'évaluation de l'activité catalytique a été réalisée dans réactions couplage de Suzuki-Miyaura. De bonnes performances ont pu être observées permettant d'obtenir des taux de transformation de 99% avec des quantités de catalyseur descandant jusqu'à 0.08 mol%. L'étude de conformation ainsi que les résultats catalytiques en catalyse n'ont pas permis de mettre en évidence un effet supramoléculaire de la cavité macrocyclique envers le processus de couplage. Dans le but d'orienter le centre catalytique à l'intérieur de la cavité, des contraintes stériques ont été appliquées sur des nouveaux Pd-NHC-complexes. Ainsi des complexes dimeriques de palladium ont été synthétisés et entièrement caractérisés. Plusieurs approches pour construire des linkers intramoléculaires permettant de fixer la conformation ont été énvisagées mais n'ont pas permis à ce jour un gel conformationnel
This thesis will focus on development of N-heterocyclic carbene palladium complexes based on calix[4]arenes: from synthesis, characterization and structural study to evaluation of catalytic activity. A new series of calix[4]arene supported N-heterocyclic carbene palladium complexes was developed and fully characterized. A mono-substituted calix[4]arene was prepared through conventional procedures, following with the attachment of imidazolyl derivative groups to compose the precursors of novel NHCs ligands. Undergoing the alkylation with n-butylbromide and corresponding metallation with palladium and pyridine, original complexes were obtained. After a full characterization in solution and solid state, the evaluation of catalytic activity was undertaken through Suzuki-Miyaura cross-coupling reactions which revealed good performances. The conformational study as well as the catalytic results in catalysis did not allow putting in evidence a supramolecular effect of the macrocycle cavity towards the coupling process. With the aim of localize catalytic center inside of the cavity, steric constrain was involved in the form of new Pd-NHC-complexes. Dimeric Pd complexes were synthesized and fully characterized as well. Several approaches to construct intramolecular linkers for fixing the conformation were elaborated. The conception of ‘flexible steric bulky’ inspired the research on confined structure of calix[4]arene, such as encapsulation and capped configuration. Relative progresses were carried out and discussed

Les carbènes N-hétérocycliques (NHC) sont connus pour être de bons ligands des métaux de transition (TM). Dans ce manuscrit, le premier chapitre est consacré une présentation non exhaustive des différentes approches qui ont été utilisées dans la littérature pour le design de NHCs chiraux efficaces en catalyse enantiosélective. Au début du deuxième chapitre, le nouveau concept est présenté. Celui-ci repose sur la formation d’un axe de chiralité qui est créé lors de la coordination du ligand NHC à un métal de transition. Ce chapitre est consacré à la synthèse de complexes possédant une symétrie C1. Différents sels d’imidazolium, précurseurs des NHCs, ont été synthétisés et utilisé pour former des complexes palladium. Ils ont été sous forme énantiopure par HPLC chirale à l’échelle préparative. Ces complexes ont fait l’objet d’études concernant leurs propriétés chiroptiques et leurs barrières de rotation avant d’être testé en catalyse. Le concept a été ensuite étendu pour la synthèse de complexes d’or et de cuivre. Ces derniers se sont avérés être intéressants car non seulement ils ont permis d’obtenir de bons excès énantiomériques en catalyse mais leurs utilisations comme agent de transfert de ligands NHC a permis de proposer un mécanisme pour le procédé de transmétallation. Le troisième chapitre fait état des travaux qui ont été réalisés sur la préparation de complexes chiraux NHC-TM possédant une symétrie C2. Différents sels d’imidazolium symétriques ont été synthétisés et utilisés pour former des complexes de palladium. Les versions homochirales de ces complexes se sont avérées être d’excellents catalyseurs chiraux pour la réaction l’α-arylation d’amides (jusqu’à 98% ee)
N-heterocyclic carbenes (NHC) are recognized to be excellent ligands towards transition metals ™. In this manuscript, the first chapter is dedicated to a non-exhaustive presentation of the various approaches of the literature which have been used to design chiral NHCs efficient in enantioselective catalysis. As a prelude of the second chapter, the new concept lies on the formation of an axis of chirality during the coordination between the NHC ligand and the transition metal. This chapter is dedicated to the synthesis of complexes with a C1 symmetry. Various imidazolium salts, have been synthesized and then used to generate palladium complexes. These complexes have been obtained in a enantiopurically form thanks to a chiral HLPC resolution at a preparative scale. These homochiral complexes were firstly subjected to studies aiming the investigation of their chiroptic properties and the determination of their rotation barriers values. The concept was then successfully extended to the synthesis of gold- and copper-based complexes. Homochiral copper-NHC complexes were found of particular importance since their applications in catalysis allowed to reach good enantioinductions and as NHC transfer reagents brought some experimental proofs on the transmetalation process. The third chapter disclosed the works that have been done on the preparation of heterochiral NHC-TM complexes possessing a C2 symmetry. Various symmetric imidazolium salts have been synthesized and then used to form the corresponding palladium-based complexes. Homochiral complexes were found displaying good activities for α-arylation of amides and excellent enantioselectivities (up to 98% ee)

Nowadays, the requirement to design highly valuable compounds is undoubtedly one of the major challenges in the field of organic and organometallic chemistry. The use of the versatile and efficient N-heterocyclic carbenes (NHCs) combined with transition metals represents a key feature in modern organometallic chemistry and homogeneous catalysis. In the course of this thesis, the straightforward design and synthesis of a library of Pd(0) bearing NHC ligands was achieved. Their catalytic performances (Chapter 1) and their phosphorescence properties in solution (Chapter 2) were disclosed. Currently, cross-couplings are some of the most important types of reaction in palladium catalysis. The formation of highly hindered biaryls substrates is one of the main requirements in cross-coupling chemistry. The design and synthesis of a palladium dimer bearing a bulky NHC ligand can fulfil this proposal (Chapter 4). The development of new classes of ligands is a topic of interest. For this reason, normal, abnormal, remote and mesoionic N-heterocyclic carbenes copper complexes were investigated and their reactivity compared in the [3+2] cycloaddition of azides and alkynes (Chapter 7). Air and moisture stable Cu(I)-NHC species have also been compared to their silver analogues for the alkynylation of ketones (Chapter 9). The different reactivity of the two latter organometallic species (Cu and Ag) with ethyldiazoacetate reagent via the formation of carbenes or C-H activated product is presented in Chapter 8. Recently, the development of a bimetallic catalytic system is strongly considered and has high impact. For this reason, two dual catalytic transformations (Pd-NHC and Cu-NHC) were studied for the C-H arylation (Chapter 5) and the synthesis of substituted alkenes products via a relay or cooperative mechanisms (Chapter 6). The isolation of intermediates and mechanistic studies were examined in each of these studies.

En plus du site de coordination interne classique des porphyrines, il est possible de fonctionnaliser le macrocycle par des sit es de coordination externes. Ce travail de thèse porte sur la fonctionnalisation de deux carbones b-pyrroliques adjacents afin d'obtenir des porphyrines conjuguées avec des ligands de type carbène N-hétérocyclique (CNH).Les CNHs présentent de remarquables propriétés électroniques qui en font aujourd'hui des ligands incontournables en catalyse et en chimie organométallique. L'objectif de ce travail de thèse a été d'étudier l'influence de la porphyrine sur les propriétés électroniques du ligand périphérique CNH, et de moduler les propriétés électroniques et catalytiques de complexe métalliques en fonction des modifications chimiques apportées à la porphyrine, à savoir sa métallation ou la protonation des azotes de la porphyrine base-libre.Dans un premier temps, les différentes méthodes de synthèse développées afin d'obtenir différents sels d'imidazolium conjugués avec le macrocycle porphyrinique sont développées. Ces sels d'imidazolium sont les précurseurs des ligands porphyrine-CNH. Afin d'étudier les propriétés catalytiques de complexes contenant des ligands de type porphyrine-CNH, plusieurs complexes de palladium(II) ont été synthétisés et caractérisés. Les études des propriétés catalytiques de ces complexes testées sur le couplage de Heck ont démontré que de bien meilleures activités catalytiques étaient observées si les porphyrines contiennent un cation métallique. Enfin, les propriétés des ligands CNH ont été étudiées sur des complexes de types (CNH)Rh(COD)X et (CNH)Rh(CO)2X avec X = I ou Cl
In addition to the usual inner coordination site of porphyrins, it is possible to functionalize the macrocycle by external coordination sites. This PhD thesis is devoted to the functionalization of two neighboring b-pyrrolic carbons in order to obtain porphyrins fused to peripheral N-heterocyclic carbene ligands (NHC).NHC ligands are known to display outstanding electronic properties which render them important ligands in the fields of catalysis and organometallic chemistry. The aim of this PhD work was to study the influence of the porphyrin on the electronic properties of the peripheral NHC ligand, and to modulate the electronic and catalytic properties of anchored metal complexes according to the chemical modifications brought to the porphyrin, ie. its metallation or the protonation of the free-base porphyrin.Firstly, the different synthetic procedures to obtain porphyrins fused to imidazolium rings were developed. These imidazolium salts are the key precursors of the porphyrin-NHC ligands. In order to study the catalytic properties of metal complexes containing porphyrin-NHC ligands, several palladium(II) complexes were synthesized and characterized. The study of the catalystic properties of these complexes showed that better catalytic activities were observed if the porphyrins contain a metal cation. Then, the electronic properties of these NHC ligands were evaluated for (NHC)Rh(COD)X and (NHC)Rh(CO)2X complexes with X = I or Cl

Se ha obtenido una nueva familia de cuatro Complejos Organometálicos Supramoleculares (SOCs) basados en pireno. Dentro de los cuales se ha desarrollado un nuevo receptor de PAH, capaz de discernir entre los diferentes PAH en función de su forma, tamaño, y número de electrones-pi. Hemos desarrollado una estrategia eficiente para la extracción de PAH, que son compuestos tóxicos y carcinogénicos, en disolventes orgánicos. Paralelamente, se han obtenido dos receptores de fulereno, capaces de adaptar su tamaño a la forma del fulereno. Debido a la mayor afinidad respecto a un fulereno específico, mostramos un potencial nuevo método de purificación de fulerenos. Describimos el primer sistema host-guest utilizado como fotosensibilidazor en la generación de oxígeno singlete. Este SOC con fulereno atrapado, fue capaz de oxidar una gran variedad de alquenos utilizando el oxígeno singlete generado a partir de aire a presión atmosférica y luz visible. Finalmente se encapsularon multiples guests.
Three nickel-based and one palladium-based supramolecular organometallic cages have been prepared. These four cages are based on a N-heterocyclic carbene ligand with a pyrene tag, that has been key in the subsequent applications of the cage together with the inner cavity. By pi-stacking interactions, it has been possible to encapsulate both polycylic aromatic hydrocarbons and fullerenes. The interest on first group of compounds is based on their accurate toxicity while the fullerenes are interesting due to their added value. It was possible to extract the first group of molecules from an organic media through the encapsulation inside the supramolecular cages. The host-guest adduct formed with fullerenes encapsulated inside the palladium cage was used as photocatalyst of aromatic, cyclic and acyclic substrates via singlet oxygen generation. The same palladium cage was used as receptor for multiple stacks of polyaromatic compounds.
Programa de Doctorat en Ciències

Ce mémoire est consacré à la synthèse et à l'étude de complexes métalliques originaux contenant des carbènes N-hétérocycliques (NHCs) fortement encombrés. Trois familles ont été élaborées : 1) des complexes Pd-PEPPSI "dissymmétriques" comportant un ligand imidazolylidène (Im) ayant comme N-substituants un groupe 9-alkyl-9-fluorényle (AF) ainsi qu'un aryle. Ces complexes se sont avérés des catalyseurs remarquables en couplage de Suzuki-Miyaura, présentant des performances comparables à celles d'analogues porteurs de deux groupes AF (dont l'excellente efficacité avait déjà été établie), démontrant ainsi le fort rôle stabilisateur du groupe AF; 2) des complexes trigonaux de cuivre(I) de formule générale [Cu(Im)(2,2'-dipyridylamine)]BF4 où le ligand carbénique est soit un carbène symétrique de type AF2-Im, soit dissymétrique de type (AF,Ar)-Im. Ici encore, la présence de substituants AF est un élément favorisant la stabilité des complexes en solution par rapport à une décomposition photo-induite. Contrairement à son anaolgue ayant un imidazolylidène porteur de deux substituants EtF, le complexe [Cu((EtF,Ph)-Im)(2,2'-dipyridylamine)]BF4 présente la particularité d'être luminescent en solution et à l'état solide; 3) des complexes Pd-PEPPSI contenant un imidazolilydène N-substitué par deux groupes identiques dont les extrémités sont des récépteurs potentiels de type calix[4]arène. Ces complexes ont la propriété de s'auto-assembler en formant une entité où les centres métalliques sont stériquement très protégés, avec pour conséquence de modifier sensiblement les propriétés catalytiques attendues du complexe
Described herein are the stepwise syntheses and properties of three types of complexes based on sterically encumbered N-heterocyclic carbenes (NHCs): 1) Pd-PEPPSI complexes with an unsymmetrical imidalolylidene ligand having its N atoms substituted by a bulky 9-alkyl-9-fluorenyl (AF) group and an aryl group. These turned out to be very active Suzuki-Miyaura cross coupling catalysts with an activity comparable to previously reported, highly performing "symmetrical" analogues which bear two identical AF substituents. These findings illustrate the high stabilising effect of each individual AF group; 2) Trigonal copper(I) complexes with the general formula [Cu(Im)(2,2'-dipyridylamine)]BF4 in which the NHC ligands are symmetrical or not. Here again the AF substituents ensure complex stability with respect to air when compared to analogues displaying sterically non-bulky substituents. One of the complexes, namely [Cu((EtF,Ph)-Im)(2,2'-dipyridylamine)]BF4, was found to be strongly luminescent in solution and in the solid state; 3) Pd-PEPPSI complexes in which calix[4]arene-substituted phenyl moieties have been grafted on both N atoms, these behaving as potential receptor units. Owing to the presence of the calixarene termini, complexes of this type were found to self-assemble, thereby resulting in dimers with sterically highly protected metal centres. The formation of such species was correlated to the catalytic performance of these complexes

The present research project concerns the catalytic application of transition metal dicarbene complexes in aromatic C-H bond functionalisation/activation reactions. The efficiency of this kind of complexes has been mainly examined in the hydroarylation of alkynes (Fujiwara reaction), which involves the addition of arenes to a wide range of internal and terminal alkynes. It was already known that this reaction is catalysed by simple palladium(II) compounds, such as Pd(OAc)2, in a trifluoroacetic acid environment. It occurs at room temperature and is characterised by a high and quite unusual regio- and stereoselectivity: remarkably the thermodynamically less favoured cis-arylalkenes are often obtained as major products. The Fujiwara reaction appears very promising from the synthetic point of view also because both the inter- and intra-molecular versions of the reaction are known, thus expanding its applicability to the functionalisation of aromatic heterocycles and to the synthesis of coumarins. However, the possible industrial application requires the optimisation of the reaction conditions since the reaction is often quite slow, needs an excess of arene substrate, and it usually requires 1-5 mol% palladium which heavily affects the cost of the process. In the literature other metal centres, such as platinum(II), gold(I) and gold(III) have been successfully employed as alternative catalysts, but their efficiency appears to be lower than that of palladium(II). Also the use of non-noble, electrophilic metal centres has been reported, but their reactivity is lower and/or their applicability limited to aryl-acetylenes. The initial aim of the present research project was to improve the yields of the reaction and decrease the catalyst loading. N-heterocyclic carbene ligands can improve the stability of the catalyst under the reaction conditions as well as its reactivity. Monocarbene Pd(II) complexes (IPr)Pd(OAc)2 and (IPr)Pd(OOCCF3)2 (IPr = N,N’-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene) are indeed the only complexes which have been reported to be active in the Fujiwara reaction in the absence of other promoters, though their activity is comparable to that of simple Pd(OAc)2. In the initial part of this research work it has been shown that dicarbene palladium(II) complexes are able to catalyse the hydroarylation of alkynes at 80 °C, with excellent conversions and selectivities at low catalyst loading (0.1 mol%) and with equimolar amounts of reagents. These dicarbene complexes have displayed a reactivity higher than simple palladium acetate and monocarbene palladium complex (12) tested in the same reaction conditions. Dicarbene platinum(II) complexes have also been employed and have performed an efficiency superior than Pt salts based systems reported in the literature. The optimised protocol has resulted quite general with respect to the alkyne, while its applicability to arene substrates is at present limited to electron-rich molecules. However this is a limitation occurring with all Pd- and Pt-catalytic systems reported in the literature for the hydroarylation reaction. Another part of the work has concerned the identification of the catalytic active species. Mechanistic studies, performed at 80 °C and made varying both the dicarbene ligand and the halide ligands at the metal, have revealed that the catalytic active species retains the dicarbene ligand in its coordination sphere. Halide anionic ligands are instead removed from the complex by exchange with the trifluoroacetate anion deriving from the acidic solvent media. The catalytic efficiency of the complex does not depend on the kind of halide ligands, but it is influenced by the nature of the dicarbene ligand. Parallel electrochemical studies have been therefore made to evaluate the electronic density at the metal centre in different dicarbene complexes. The aim is to clarify if the catalytic efficiency of the complex is predominantly influenced by its electronic or steric properties, in order to design the best catalyst for the reaction. Cyclic voltammetries have shown that the electronic density at the metal changes depending on the dicarbene ligand, but the scale of reduction potentials Pd(II)-Pd(0) is not correlated to the scale of catalytic activity. This suggests that the catalytic efficiency of such complexes in the Fujiwara reaction is predominantly influenced by the steric hindrance at the metal centre. A successive optimisation of the reaction parameters (nature of the solvent system, concentration of the reagents, reaction temperature and use of co-catalysts) has allowed to further increase the selectivity of the reaction under mild reaction conditions. It has indeed found that, in the presence of silver salts (like AgTFA) as co-catalysts, the reaction can be run at room temperature, with conversion higher than the one displayed by palladium acetate in the same reaction conditions. Differently from at 80 °C, isomerisation to the more thermodinamically stable trans-arylalkene and hydrolysis reactions of the ester functions do not occur at room temperature, so that selectivity towards the cis-arylalkene product has been significantly improved. Finally, the optimised catalytic system has been used with other substrates, such as aromatic heterocycles, obtaining also in this case high yields in products. However, the selectivity towards the desired product decreases by the formation of adducts heterocycle/alkyne 2/1. A preliminary investigation of the reaction mechanism through kinetic studies has been also started. There is indeed at present some controversy about the reaction mechanism, that could be an electrophilic arene metalation or a Friedel-Crafts-type alkenylation. The kinetic law has resulted of the first order in palladium and, in the adopted reaction conditions, of the first order also in arene or in alkyne. It remains to evaluate the dependence of the kinetic law from the concentration of the acid, which seems to have an important role in the reaction mechanism. However, it needs to be used in large excess with respect to the substrates and probably its principal role is to hydrolyse the vinyl-palladium species, invoked as catalytic intermediate in both the proposed mechanisms. Dicarbene complexes of palladium(II) and platinum(II) have been also tested in other aromatic C-H bond functionalisation reactions, such as the ortho-functionalisation of acetanilides.
Il presente progetto di ricerca riguarda l’applicazione di complessi dicarbenici di metalli di transizione in reazioni di funzionalizzazione/attivazione di legami C-H aromatici. L’efficienza catalitica di questi complessi è stata principalmente valutata nella reazione di idroarilazione di alchini (reazione di Fujiwara), che consiste nell’addizione di areni ad alchini interni o terminali catalizzata da semplici composti di palladio(II), come Pd(OAc)2. Questa reazione decorre in ambiente acido, generalmente acido trifluoroacetico, a temperatura ambiente e presenta una elevata ed inusuale regio- e stereoselettività: si ottengono infatti come prodotti principali i cis-arilalcheni, che sono le olefine termodinamicamente meno favorite. La reazione appare molto promettente dal punto di vista tecnologico, anche perché sono conosciute sia la versione inter- che quella intramolecolare, permettendo quindi la funzionalizzazione di eterocicli aromatici e la sintesi di cumarine. La potenziale applicazione industriale richiede però l'ottimizzazione delle condizioni di reazione, poichè la reazione è spesso lenta, necessita di un eccesso di arene rispetto all’alchino e viene condotta con un elevato tenore di catalizzatore (1-5%), fattore che incide pesantemente sul costo del processo. Altri centri metallici, come Pt(II), Au(I) e Au(III), sono stati impiegati come catalizzatori alternativi, ma la loro reattività sembra essere inferiore a quella mostrata dai composti di palladio(II). Sono stati utilizzati anche centri metallici elettrofilici non nobili, ma la loro reattività è inferiore e/o la loro applicabilità limitata ai soli aril-acetileni. L’obiettivo iniziale di questo progetto di tesi è stato quindi quello di migliorare le rese della reazione e diminuire il tenore di catalizzatore. Leganti carbenici N-eterociclici possono aumentare la stabilità del catalizzatore nelle condizioni di reazione e quindi la sua reattività. I complessi monocarbenici di palladio(II), (IPr)Pd(OAc)2 e (IPr)Pd(OOCCF3)2 (IPr = N,N’-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene) sono infatti gli unici complessi ad essere risultati attivi nella reazione di Fujiwara senza bisogno di promotori, sebbene la loro reattività sia comparabile a quella mostrata da Pd(OAc)2. Nella prima parte di questo lavoro di ricerca è stato dimostrato che complessi dicarbenici di palladio(II) catalizzano la reazione ad 80 °C, con eccellenti conversioni e selettività a basso tenore di catalizzatore (0.1%) e con i reagenti in rapporto equimolare. Questi complessi hanno mostrato una reattività maggiore rispetto al semplice palladio acetato ed al complesso monocarbenico (12) testati nelle stesse condizioni di reazione. Sono stati impiegati in questo studio anche complessi dicarbenici di Pt(II), che si sono dimostrati più attivi dei sistemi catalitici di platino riportati in letteratura. Il protocollo ottimizzato è risultato abbastanza generale per quanto riguarda gli alchini, mentre la sua applicabilità agli areni è al momento limitata a molecole elettron-ricche. Questa è comunque una limitazione di tutti i sistemi catalitici di Pd e Pt riportati in letteratura per l’idroarilazione di alchini. Una seconda parte del lavoro ha riguardato l’identificazione della specie cataliticamente attiva. Studi meccanicistici condotti ad 80 °C, variando sia il legante dicarbenico che i leganti anionici al metallo, hanno mostrato che la specie cataliticamente attiva mantiene il legante dicarbenico nella sua sfera di coordinazione, mentre i leganti anionici vengono rimossi dal complesso attraverso uno scambio con l’anione trifluoroacetato derivante dal solvente acido. L’efficienza catalitica del complesso non dipende dal tipo di leganti anionici, ma dipenda invece dalla natura del legante dicarbenico. Sono stati inoltre effettuati studi elettrochimici per determinare la densità elettronica presente al centro metallico in complessi con diverso legante dicarbenico, con lo scopo di chiarire se l’efficienza del complesso sia principalmente influenzata dalle proprietà elettroniche o da quelle steriche di questo legante e di progettare così il migliore catalizzatore per la reazione. Le voltammetrie cicliche hanno mostrato che la densità elettronica al centro metallico varia a seconda del legante dicarbenico, ma che la scala di potenziali di riduzione Pd(II)-Pd(0) non è correlabile alla scala di attività catalitica. L’efficienza di questo tipo di complessi nella reazione di Fujiwara sembra quindi essere principalmente influenzata dall’ingombro sterico al centro metallico. La successiva ottimizzazione dei parametri di reazione (natura del solvente, concentrazione dei reagenti, temperatura di reazione ed utilizzo di co-catalizzatori) ha permesso di incrementare ulteriormente la selettività della reazione in condizioni di reazione blande. E’ stato infatti dimostrato che in presenza di sali di argento come co-catalizzatori (per esempio AgTFA) la reazione avviene anche a temperatura ambiente, con conversioni maggiori di quelle ottenute con palladio acetato nelle stesse condizioni di reazione. Diversamente che a 80 °C, le reazioni di isomerizzazione a trans-arilalchene (prodotto più stabile termodinamicamente) e le reazioni di idrolisi delle funzioni esteree non avvengono a temperatura ambiente, cosicché la selettività verso il cis-arilalchene viene notevolmente migliorata. Infine, sono state determinate le condizioni sperimentali adatte per estendere questo protocollo sintetico ad eterocicli aromatici, ottenendo anche in questo caso elevate rese nei prodotti. La selettività della reazione verso il prodotto desiderato è però diminuita dalla formazione di addotti eterociclo/alchino 2/1. Analisi preliminari di tipo cinetico hanno inoltre dato una prima indicazione sul tipo di meccanismo coinvolto nella reazione, che non è ancora del tutto chiarito e che potrebbe coinvolgere la metallazione elettrofilica dell’arene oppure una alchenilazione di tipo Friedel-Crafts. La legge cinetica è risultata essere del primo ordine in palladio e, nelle particolari condizioni dei reazione adottate, anche del primo ordine in arene o in alchino. Rimane da valutare la dipendenza della legge cinetica dalla concentrazione di acido, che sembra avere un ruolo importante nel meccanismo di reazione. Deve essere infatti utilizzato in largo eccesso rispetto ai substrati e probabilmente il suo ruolo principale è quello di idrolizzare la specie vinilica di palladio, proposta come intermedio catalitico in entrambi i cicli riportati in letteratura. I complessi dicarbenici di palladio(II) e platino(II) sono stati testati anche in altre reazioni di funzionalizzazione di legami C-H aromatici, come l’orto-funzionalizzazione di acetanilidi.

The first chapter is an introduction to the f-elements, with a focus on the synthesis and chemistry of tetravalent cerium complexes. The synthesis, characterisation and reactivity of carbenes, particularly N-heterocyclic carbenes (NHCs), and anionic-functionalised NHC ligands is discussed. The synthesis and reactivity of s-block, Group three and fblock NHC complexes is reviewed. The synthesis of the alcohol-functionalised unsaturated imidazolium proligand, [H2L]I [H2L = HOCMe2CH2(1-CH{NCHCHNiPr})], is extended to saturated imidazolinium analogues, [H2LR]X, [HOCMe2CH2(1-CH{NCH2CH2NR})]X (R = iPr, abbreviated to P; R = Mes, abbreviated to M; R = Dipp, abbreviated to D, X = Cl, I). Mono-deprotonation results in the isolation of bicyclic imidazolidines HLR, which can be ring-opened and silylated by treatment with Me3SiI, to afford [HLR, OSiMe3]I, R = iPr and Mes. Further deprotonation of HLR with MN"2 (M = Mg, Zn; N" = N(SiMe3)2) affords LRMN" (M = Mg and Zn) and ZnLR 2. These complexes proved active for the polymerisation of raclactide at room temperature without the need for an initiator. The third chapter focuses on cerium chemistry. Repetition of the literature synthesis of CeIV tert-butoxide compounds affords the unsolvated Ce(OtBu)4 and also the cluster Ce3(OtBu)11. Treatment of Ce(OtBu)4 with HL did not yield a CeIV-NHC complex, but one bearing a tethered imidazolium group, (OtBu)3Ce( -OtBu)2( -HL)Ce(OtBu)3. The synthesis of a CeIII-NHC complex, CeL3, and the oxidation of this forms an unprecedented CeIV-NHC complex, CeL4, via ligand redistribution; the complex contains two bidentate ligands and two alkoxide-tethered free NHC groups. Functionalisation of the free NHCs with boranes affords the adducts Ce(L)2(L-B)2, where B = BH3 or 9-BBN (9-Borabicyclo[3.3.1]nonane). A number of cerium complexes of the saturated-backbone NHC, LR, LRCeN"2 and LR 2CeN", have been synthesised and their oxidation chemistry and reactivity investigated. The final chapter contains an NMR study of the synthesis of a series of yttrium LR adducts, LP xYN"(3-x) (x = 1, 2 or 3), and of the synthesis of uranium complexes LRUN"2, R = Mes or Dipp, including a range of small molecule reaction chemistry. The uranyl NHC complexes, UO2LR 2, R = Mes or Dipp, have also been synthesised and characterised; these possess very high frequency carbene carbon chemical shifts.

A library of chiral and achiral imidazolium salts was prepared, and evaluated as potential pre-catalysts of the benzoin condensation.  It was found that although the carbenes derived from these compounds possess catalytic activity, this was not as pronounced as that observed for alternative heterocycle classes.  Asymmetric induction, although observed from imidazolylidenes for the first time in this work, is not of an order that could be considered useful, as has been seen for other NHC catalysts.  This is attributed to the use of harsh reaction conditions, required to promote catalytic activity in this system. Two modifications were thus made to the imidazolium salt pre-catalysts in an attempt to make the reaction conditions less extreme.  Imidazolium carboxylates were found to be suitable pre-catalysts, thus allowing the reaction to be performed under neutral conditions.  Purinium salts were also investigated, based on the theory that these more electron deficient fused heterocycles would allow access to carbenes under milder conditions.  Although problems were encountered in the synthesis of these salts, one example was prepared, however the available data indicate this exists as the incorrect regioisomer. Two strategies for catalyst immobilisation have also been investigated.  It was found that polymer supported imidazolylidenes are capable of catalysing the benzoin condensation of a range of aromatic aldehydes, under a range of conditions, and can undergo a limited number of recycles.  Imidazolium salts supported on silica were found to be unsuitable for the catalysis of this reaction.  This was blamed on incompatibility of the persistently acidic matrix with the basic conditions required by the carbene. Application of imidazolylidenes to the intra-molecular Stetter reaction was also attempted, however this revealed NHC have the ability to act catalytically as bases.  Further investigation of this observation suggested the effect is limited to α,β-unsaturated carbonyl compounds.

The syntheses of a new class of polycyclic TriAmino DiCarbenes (TADCs), based on 3,9-diazajulolidine, and their precursors and adducts are described. Starting with 2,6-dimethyl-nitrobenzene, 2,6-bis ((alkylamino)methyl)anilines (alkyl = isopropyl, mesityl, and tert-butyl) were synthesized in 40% yield over five steps. These triamines were then di-cyclized stepwise to diformamidinium dications or formamidinium/2-methoxyformaminals using oxonium salts and trialkyl orthoformates. A diformamidinium dication was characterized by single-crystal X-ray diffractometry. Treatment with various bases, particularly lithium hexamethyldisilylazide, led to the novel TADCs and monocarbenes, two of which were isolated and characterized by 1H and 13C NMR spectroscopies. In both cases, treatment with elemental sulfur trapped the TADCs as dithiobiurets. No TADC-transition metal complexes were successfully isolated from reactions of the diformamidinium dications or LiHMDS TADC complex with a number of transition metal complexes. With the exception of these two cases, all other TADCs were not isolated because they rapidly reacted to form dimers, trimers, and tetramers. One of these dimers was isolated and its structure determined using 1D and 2D NMR spectroscopies, along with high-resolution electrospray ionization mass spectrometry. This revealed that the TADC had dimerized to form an ene-triamine, likely via 1,3-shift of a benzylic proton. Novel N-heterocyclic Carbene (NHC) complexes of molybdenum were also synthesized and characterized. Reaction of Cp2Mo2(CO)4 (Cp = C5H5) with dimesityl-imidazol-2-ylidenes (IMes) or dimesityl-imidazolidin-2-ylidenes (SIMes) yielded the molybdoradicals CpMo(CO)2(NHC) (NHC = IMes or SIMes). The carbonyl infrared stretching frequencies and the relative metal-to-NHC π-backbonding for IMes and SIMes complexes are compared. Reaction of the less bulky dimethyl-imidazol-2-ylidene (IMe) with Cp2Mo2(CO)4 yielded the Mo-Mo triple bond complex Cp2Mo2(CO)3(IMe) by CO substitution. This is the first example of an NHC-ligated metal-metal multiply bonded complex. Single crystal X-ray diffractometry of these new organomolybdenum and organodimolybdenum complexes is discussed.

Transition metal-based catalysts are one of the most powerful tools available to chemists and the development of ligand systems with which to modify their activity is a constant area of research. In the last twenty years N-Heterocyclic carbenes (NHCs) have established themselves at the forefront of organometallic chemistry. To increase the lifetime of the catalyst these ligands are increasingly being immobilised on supports as, this allows recovery and reuse while attempting to retain the activity. Cleaner, greener and safer processes are increasingly important and the recovery of the catalyst by simple separation also removes contamination and enables the possibility of re-use. This thesis describes the development of a new concept to immobilise transition metal complexes through an N-heterocyclic carbene ligand. The introductory Chapter provides an overview of transition metal catalysis, introducing the use of supported catalysis including the use of magnetic nanoparticles to aid the recovery of the catalyst systems. A discussion is included of N-heterocyclic carbene ligands, including their synthesis, activity in catalysis as ligands for metal complexes as well as attempts to support the systems and their use in various reactions. Chapter 2 provides an in-depth introduction to palladium catalysis, focusing on cross-coupling and dehalogenation reactions. The design of palladium catalysts, concentrating on palladium-NHC complexes and covers the use of supported catalysts. The synthesis and immobilisation of a novel palladium carbene complex is also described. The supported and unsupported complexes were screened in the Suzuki-Miyaura reaction and dehalogenation reaction. The activity and recycling properties of the supported catalyst system are discussed. The next Chapter outlines the use of copper-NHC complexes in the 1,3-dipolar cycloaddition reaction of azides and alkynes to form 1,2,3-triazoles. The preparation and characterisation of a novel N-heterocyclic carbene ligand is described, along with the construction of the supported copper systems. These catalysts were then investigated in the cycloaddition reaction and assessed for their activity and recovery. The scope of the reaction is also explored, investigating functional group tolerance. The final Chapter contains experimental procedures and characterisation data for all compounds synthesised during this project.

Parmi les agents thérapeutiques utilisés en chimiothérapie, la molécule la plus connue et utilisée dans le monde est le cisplatine ou cis-diamminedichloroplatinum(II) démontrant le potentiel des métaux en chimie médicinale. Malheureusement, le cisplatine engendre de nombreux effets secondaires importants et une résistance cellulaire. Dans la quête de nouveaux agents anticancéreux, les complexes de carbènes N-hétérocycliques (NHC) de métaux de transition constituent des candidats prometteurs. C’est dans ce contexte que s’est inscrit l’objet du projet de thèse qui a consisté en la synthèse et l’étude de nouveaux complexes NHC cytotoxiques de métaux de transition (notamment le platine). Deux nouvelles voies de synthèse simples, reproductibles et facilement modulables ont été développées permettant la fonctionnalisation post-complexation de composés NHC (a) par réaction de cycloaddition 1,3-dipolaire et (b) par substitution sélective de ligand. Ces stratégies de fonctionnalisation ont alors été étendues à l’accrochage des molécules hydrosolubles, d’agents permettant le ciblage sélectif des cellules tumorales par interaction avec des récepteurs spécifiques souvent surexprimés dans le cas des cellules tumorales ou encore d’agents fluorescents. Les activités cytotoxiques de ces nouveaux composés ont été mesurées in vitro sur une variété de lignées cellulaires cancéreuses. Pour la majorité de ces composés, les activités observées sont supérieures à celle du cisplatine et certains ont également démontré une sélectivité vis-à-vis des cellules tumorales. Ces premiers résultats encourageants ouvrent ainsi de nouvelles perspectives thérapeutiques en cancérologie
Among the existing anticancer agents, cisplatin or cis-diamminedichloroplatinum(II), represents the most known and commonly used chemotherapeutic drug worldwide highlighting the potential of metals in medicinal chemistry. However, its clinical effectiveness is also accompanied by severe side toxicities and cell-resistance mechanisms. These therapeutic limitations have encouraged the development of substitutes to cisplatin and have led to the discovery of N-heterocyclic carbene (NHC) complexes of several late transition metals as new anticancer agents with similar to higher in vitro activities than cisplatin. In this context, the present project dealt with the synthesis and the study of novel cytotoxic NHC complexes of some transition metals (mainly platinum). Two simple, reproducible and modular synthetic routes were developed for the easy functionalization post-complexation of NHC derivatives using (a) ruthenium-catalyzed alkyne-azide cycloaddition and (b) ligand substitution. In order to improve the efficacy and selectivity of the NHC complexes, we have extended these strategies of functionalization to the attachment of biologically interesting moieties such as targeting agents, hydrosoluble groups and fluorescent dyes. In vitro cytotoxic activities of these newly synthesized complexes were measured against a wide variety of cancerous cells. The majority of the compounds demonstrated higher activities than the benchmark cisplatin and some were selective toward tumoral cells. These promising early-stage results offer new perspectives in cancer therapy while giving alternatives to the biomedical limitations of cisplatin

This thesis describes the synthesis of new N-heterocyclic carbene complexes through the synthesis of 1,4-bis-substituted imidazolium salts or tricyclic saturated imidazolium salts. The introduction highlights some of the most successful methods for preparing N-heterocyclic carbenes and corresponding metal complexes. Examples of the use of these complexes in transition metal-catalysed processes are provided towards the end of this chapter. The second chapter is dedicated to our efforts to synthesize 1,4-bis-substituted imidazolium salts as precursors for the synthesis of N-heterocyclic carbene complexes. The first part of this chapter describes the synthesis of 1,4-bis-substituted imidazolium salts using 1,4-bis-substituted diazabutadienes. Following this, attempts to deprotonate imidazolium salts to afford the desired N-heterocyclic carbenes are discussed. On the basis of the results obtained for the synthesis of 1,4-bis-substituted imidazol-2-ylidenes, the synthesis of N-heterocyclic carbene complexes, where the carbene is generated in situ are explored at the end of this chapter. The synthesis of enantiomerically pure tricyclic saturated imidazolium salts via enantiomerically pure diamines is discussed in the third chapter. Firstly, different methods were tested for the preparation of diamines from 6,6'-dimethyl-2,2'-bipyridine, 2,2'-biquinoline and (S,S)-6,6-bis-(1-methoxy-2,2'-dimethylpropyl)-2,2'-bipyridine. Following this, is reported the synthesis of tricyclic saturated imidazolium salts. Suzuki cross coupling of 4-chlorotoluene with phenylboronic acid was investigated in the presence of different imidazolium salts. This chapter concludes with a few suggestions for the synthesis of enantiomerically pure 2,6-bipiperidines. The fourth chapter is the experimental section and is dedicated to the methods of synthesis and characterization of the compounds mentioned in the previous chapters. X-ray reports regarding the crystallographic representation of the structures presented in chapter two and three are provided in chapter five.