Дисертації з теми "Copper(I) N-heterocyclic carbene"

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2007.
Vita.
Includes bibliographical references.
This thesis presents work towards the development of a new catalytic C-C bond forming reaction. Alkynes and olefins insert into [(IPr)CuH]2 (IPr = N,N-bis-(2,6-diisopropylphenyl)-1,3-imidazol-2-ylidene) to give copper vinyl and copper alkyl complexes. These copper complexes insert CO2 into the Cu-C bond to form copper acrylate and copper carboxylate complexes. Acrylic and carboxylic acids can be isolated by hydrolysis. A catalytic cycle based on (IPr)copper(I) was developed. Alkynes undergo reductive carboxylation to give acrylic acids in moderate yields. Unexpected interactions between several components of the catalytic system led to a number of side reaction, most importantly between [(IPr)CuH]2 and the product silyl acrylate. The use of silylcarbonate salts to desylilate the product enhanced yield. In addition, silylcarbonates can also serve as a source of CO2.
by Gergely Sirokman.
Ph.D.

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.

As part of a worldwide effort to develop efficient catalysts for use in organic chemistry and in the synthesis of highly valuable molecules, work performed during the course of my stay in St Andrews has focused on the design and synthesis of new group 11 metal complexes for their applications in catalysis. The aim of this work was to develop new, active and stable, easy to synthesise group 11 complexes and investigate their catalytic activity as well as to try to understand their mode of action. Two different types of complexes were explored in order to develop more active catalysts: the neutral N-Heterocyclic carbene metal complexes and the cationic derivatives. More than 20 new catalysts were developed and their reactivity studied in different catalytic reactions. New hydroxide and tert-butoxide copper(I) or silver(I) complexes were developed and compared to the common NHC metal systems. Overall, the neutral NHC-metal catalysts showed to be highly active in a broad range of applications: in the methylation of amines using CO₂ as a C1 source, in a multicomponent reaction (A³ coupling) and in dual catalysis (hydrophenoxylation). Additionally, mechanistic studies were undertaken to obtain a greater understanding of these transformations and to possibly lead to the design of new generations of catalyst. Regarding the cationic NHC metal complexes, a straightforward methodology was developed leading to a library of highly stable catalysts. Bis-NHC, mixed NHC/ phosphine as well as NHC/pyridine species were efficiently synthesised using thermal or microwave heating, in high purity and yields. In addition, the effect of the presence of two different or identical ligands on catalytic reactivity was investigated in the 3+2 cycloaddition and in the alkynylation of ketones. Insight into the catalytic cycle was obtained via mechanistic studies. These showcased the release of one ligand during the catalytic cycle and the crucial role of this ligand displacement in generating the catalytically relevant active species. The results highlight the importance of understanding the reactivity of catalyst in order to develop new and improved ones.

This thesis concerns the synthesis, structural characterisation and reactivity of a range of novel organometallic complexes. The research primarily focuses on N-heterocyclic carbenes as ligands, and their coordination to copper cations. A novel electrochemical synthetic procedure for the synthesis of CuI-NHC complexes is described. It was found that this procedure was suitable for the synthesis of a wide range of CuI-NHC complexes, containing either bulky, non-bulky or base sensitive functional groups. Furthermore, the synthetic procedure was found to be highly selective, producing [Cu(NHC)X]- type complexes when X is a coordinating anion, and [Cu(NHC)2]X-type complexes when X is a non-coordinating anion. The structural chemistry of CuI-NHC complexes containing pendant N-allyl groups was explored, with the resultant complexes displaying an array of coordination geometries about the CuI centres. By careful modification of these ligands, the first example of a CuI -NHC complex containing a CuI-alkene interaction was observed. The coordination chemistry of NHC ligands containing pyridyl substituents, which act as ancillary donors, was investigated. CuI -NHC complexes containing these ligands were found to be catalytically competent in an Ullmann-type etherification reaction. Additionally, exposure of solutions of some of these CuI-NHC complexes to atmospheric conditions allowed the crystallographic characterisation of rare examples of CuII-NHC complexes. Finally, the rational synthesis of a range of unusual CuII-NHC complexes was performed, with the resulting complexes being structurally characterised. It was found that, under certain circumstances, oxidative decomposition of the NHC ligand within the coordination sphere of a copper centre can occur. The formation of 2-haloimidazolium and C-C coupled bis-imidazolium salts, via oxidative degradation, was investigated using a combined experimental and computational study.

Le sujet de cette thèse porte sur la synthèse de ligands de type bis-NHC (carbène N-Hétérocyclique) et leur réactivité vis-À-Vis des complexes d’argent(I), de cuivre(I) et de nickel(II).Après avoir exploré les différentes méthodologies de synthèse des complexes de nickel(II) bis-NHC, le but était de tester leurs activités en catalyse d’oligomérisation de l’éthylène. Une série de nouveaux complexes d’argent(I) et de cuivre(I) fut synthétisée. Cinq voies furent testées pour la formation de complexes de nickel. Les résultats les plus probants furent obtenus par transmétallation à partir des complexes d’iodure ou de bromure d’argent(I)
The purpose of this work was the synthesis of bis-NHC (N-Heterocyclic carbene) ligands, theformation of the corresponding silver(I), copper(I) and nickel(II) complexes and the assessment ofthe catalytic activity of the bis-NHC nickel(II) complexes in ethylene oligomerization. A series of new bis-NHC silver(I) and copper(I) complexes was synthesized. Five different synthetic routes were tested for the formation of nickel(II) bis-NHC complexes. The most significant results were obtained by transmetalation from the silver(I) iodide or bromide complexes

The work described herein focuses on the synthesis and characterisation of copper(I) complexes bearing N-heterocyclic carbene (NHC) ligands, their use in catalysis as well as organometallic synthesis and related reaction mechanisms. Two classes of complexes were considered: neutral NHC-Cu(I) species and their cationic analogues. Concerning the former, initial efforts were focused on the development of a general and straightforward synthetic methodology towards complexes of the type [Cu(X)(NHC)] (X = Cl, Br, I). More than 10 NHC-Cu(I) species were synthesised in high yields under mild conditions, in air and using technical grade solvents. These complexes exhibited interesting activity in the catalytic dehydrogenation of formic acid/amine adducts proving in three times more efficiency than the copper salts previously employed in such a reaction. Hydroxide- and tert-butoxide analogues showed to be efficient catalysts in the N-methylation of amines with CO₂ as carbon source, and in the dehydrogenative coupling of silanes and carboxylic acids. Experimental and computational work were carried out in order to elucidate the mechanism of these transformations. Regarding the use of these species in organometallic synthesis, homo- and heteroleptic bis-NHC-Cu(I) complexes were employed as carbene transfer reagents to other transition metals. Aside from well-known cationic gold(I) species, two novel palladium(II) analogues were isolated and fully characterised.

Thesis advisor: Amir H. Hoveyda
Chapter 1 Catalytic Enantioselective Addition of Organoaluminum Reagents Catalytic methods involving the enantioselective addition of both commercially available as well as in situ generated organoaluminum reagents are reviewed. An overview of additions to aldehydes, ketones, and imines is provided as well as the difficulties and limitations of such transformations. Furthermore, additions to unsaturation adjacent to a leaving group to form a new stereogenic center are examined. Finally, conjugate addition reactions wherein an organoaluminum reagent is added to an olefin adjacent to a carbonyl or nitro group are discussed. Chapter 2 Synthesis of Quaternary Carbon Stereogenic Centers through Enantioselective Cu-Catalyzed Allylic Substitution with Alkenylaluminum Reagents A method for the formation of 1,4-diene containing quaternary stereogenic centers through catalytic enantioselective allylic substitution is disclosed. The addition of alkyl- and aryl-substituted alkenylaluminum reagents to trisubstituted allylic phosphates is promoted by 0.5–2.5 mol % of a sulfonate-containing bidentate N-heterocyclic carbene–copper complex. Products containing a quaternary stereogenic center as well as a newly formed terminal olefin are obtained in up to 97% yield and 99:1 er with high site selectivity (>98:2 SN2’:SN2). The requisite nucleophiles are generated in situ through hydroalumination of terminal alkynes. The utility of the method is demonstrated through a concise synthesis of natural product bakuchiol. Chapter 3 A Multicomponent Ni-, Zr-, Cu-Catalyzed Strategy for Enantioselective Synthesis of Alkenyl-Substituted Quaternary Carbons Despite the widespread use of conjugate addition in organic synthesis, few reports pertain to the addition of nucleophiles to acyclic systems and none in which the nucleophile is an alkene. Herein, we report the first examples of enantioselective conjugate addition of alkenylmetal reagents to trisubstituted enones to form all-carbon quaternary stereogenic centers. Alkenylaluminum nucleophiles are prepared through a site-selective Ni-catalyzed hydroalumination of terminal alkynes and the requisite E-trisubsituted enones are the products of a regioselective Zr-catalyzed carboalumination/acylation of a terminal alkyne. Products are obtained in up to 97% yield and 99:1 er. A model for enantioselectivity, supported by DFT calculations, is proposed. Chapter 4 Formation of Tertiary Centers through Catalytic Enantioselective Conjugate Addition of Alkenylaluminum Reagents to Acyclic Enones We have developed an enantioselective NHC–Cu catalyzed synthesis of tertiary centers in acyclic systems using in situ generated alkenylaluminum reagents, as current methods typically rely on Rh-catalysis at high temperatures with alkenyl boronic acids in protic solvents. Moreover, most examples include chalcone-derived substrates, which, while more reactive, often preclude further functionalization. With the current method, we are able to couple a variety of alkenyl nucleophiles with α,β-unsaturated ketones. E- or Z-silylalkenylaluminum reagents, derived from hydroalumination of silyl-protected alkynes, lead to products in good yields and high enantioselectivities. Additionally, both the α- and β-alkenylaluminum reagents participate in the reaction. Chapter 5 Development of N-Heterocyclic Carbene–Cu Catalyzed Allylic Substitution of Diboryl Methane to Morita-Baylis-Hillman Derived Allylic Phosphates We have developed a method for the coupling of a geminyl diboron reagent with Morita-Baylis-Hillman derived trisubstituted ester-containing allylic phosphates. With 10 mol % of an in situ generated NHC–Cu complex and 1.5 equivalents of the boron reagent, we are able to form the desired product in high regio- and enantioselectivity with a 2,5-ditert-butyl containing carbene. Simple aryl substituents as well as those containing a halogen or an electron-withdrawing group furnish the desired products in up to 85% yield and 98:2 er. Alkyl-containing substrates are also competent reaction partners, although longer chain aliphatics results in slightly diminished enantioselectivity. We are pursuing the application of this method to the synthesis of α-methylene lactones which can be further functionalized to natural products like tubulin polymerization inhibitor (–)-steganone and glaucoma medication (+)-pilocarpine
Thesis (PhD) — Boston College, 2016
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry

Thesis advisor: Amir H. Hoveyda
Chapter 1. A Review of Catalytic Enantioselective Allylic Substitution (EAS) with Chiral Sulfonate Containing N-heterocyclic Carbenes (NHC). A comprehensive review of enantioselective allylic substitution reactions, which are promoted by a chiral N-heterocyclic carbene metal complex that features a unique sulfonate motif, is provided in this chapter. Reactions are classified into two categories. One class of transformations is catalyzed by a series of easily modifiable sulfonate bearing NHC-Cu complexes, with which a range of nucleophilic organometallic reagents (i.e., organozinc-, aluminum-, magnesium- and boron-based) that carry different carbon-based units are readily utilized in efficient and highly selective C-C bond forming processes. Another set of reactions exclude the use of a copper salt; catalytic amount of a sulfonate containing imidazolinium salt is capable of promoting additions of alkyl Grignard, zinc and aluminum species to easily available allylic electrophiles in a site- and enantioselective fashion. The mechanistic scenarios of both catalytic systems that account for the observed experimental data are discussed in detail. Chapter 2. Cu-Catalyzed Enantioselective Allylic Substitutions with Aryl- and Heteroarylaluminum Reagents. In this chapter, the first examples of EAS reactions of aryl- and heteroaryl-substituted dialkylaluminum reagents to a wide range of trisubstituted allylic phosphates are demonstrated through a facile and selective catalysis rendered possible by an in situ generated sulfonate containing NHC-Cu complex, delivering enantiomerically enriched olefin products that bear an all carbon quaternary stereogenic center. The requisite organometallic species are easily prepared from either the corresponding aryl- and heteroaryl halides, or through efficient and site selective deprotonation at the C-2 position of furan and thiophene; such aluminum entities are readily used in situ without the requirement of purification. Application to small molecule natural product synthesis is also carried out to illustrate the utility of the present protocol. Chapter 3. Cu-Catalyzed Enantioselective Allylic Substitutions with Alkenylaluminum Reagents. This chapter focuses on our research towards construction of enantioenriched tertiary and quaternary stereogenic centers that are substituted with two further functionalizable alkenes. The first combination of the study involves the addition of stereochemically well-defined trisubstituted alkenylaluminum reagents to disubstituted allylic phosphates; the transformation commences with a silyl-directed stereoselective hydroalumination and finishes with an enantioselective Cu-catalyzed EAS promoted by a sulfonate bearing NHC. Such reactions deliver molecules that feature silicon containing trisubstituted olefin adjacent to the tertiary stereogenic center; subsequent conversion of the versatile silicon group to a proton reveals the first set of examples that incorporate pure Z alkene in Cu-catalyzed EAS. The stereoselective and concise synthesis of naturally occurring small molecule nyasol demonstrates the utility of the above method. On a different front, Ni-catalyzed site-selective hydroalumination of terminal alkynes has opened new possibility of introducing 1,1-disubstituted olefins in Cu-catalyzed EAS in the formation of tertiary stereogenic center containing enantioenriched organic building blocks. Such catalytic hydrometallation procedure also allows efficient access to alkenylaluminums that are derived from the conventionally problematic aromatic alkynes. The importance of efficient and selective synthesis of terminal aryl-substituted alkenylaluminum species is showcased in NHC-Cu-catalyzed EAS reactions that construct all-carbon quaternary stereogenic centers; a three-step convergent synthesis of natural product bakuchiol in enantiomerically enriched form highlights the potential of the current protocol in chemical synthesis. Chapter 4 Cu-Catalyzed Enantioselective Allylic Substitutions with Alkenylboronic Acid Pinacol Ester Reagents and Applications in Natural Product Synthesis. Within this chapter, we disclose the efficient utilization of alkenylboron reagents in Cu-catalyzed EAS reactions, which lead to highly site and enantioselective formations of molecules that contain both tertiary and quaternary carbon stereogenic centers. Unlike their aluminum-based counterparts, the use of boron-based reagents allows effective delivery of sensitive organic function groups, such as a carbonyl, which would be incompatible in the hydrometallation process with dibal-H. Our efforts accumulate to the first report of incorporation of all carbon quaternary centers that are substituted with unsaturated ester and aldehyde units in the EAS products; such a method facilitates the concise diastereo- and enantioselective synthesis of Pummerer's ketone and it's trans isomer. Further development of the above protocol towards the construction of tertiary stereogenic centers requires the design of new chiral sulfonate-containing imidazolinium salts as the ligand precursors and has lead to the employment of a broader range of alkenylboron species, which feature readily functionalizable motifs. Subsequent demonstrations in enantioselective synthesis of a variety of small molecule natural products showcase the utility
Thesis (PhD) — Boston College, 2013
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry

This PhD project is focused on the synthesis, characterisation of copper(I) and silver(I) complexes with policarbenic ligands and their application in catalysis for C-C and C-heteroatom bond forming reactions. We developed an alternative synthetic pathway for copper(I) complexes in collaboration with the group of Prof. Santini of the University of Camerino. This methodic led to the preparation of the copper(I) complex 2c, which has a trinuclear structure in which every copper atom is coordinated to two imidazolin-2-ylidene rings, belonging to two tricarbenic units. Complex 2c is prepared by a transmetallation reaction starting from the iso-structural silver complex 2b; the new procedure is more low-yielding than the classical free-carbene route but leads to higher purity products. Complex 2c has the same structure of complex 1c which was prepared before the beginning of this thesys. This complex was prepared following the classical free-carbene route and it differs from 2c only for the nature of the substituent on the wingtip nitrogen atoms. The scope of this synthetic procedure was subsequently investigated using other triscarbene silver complexes prepared by Santini as well as biscarbene silver complexes prepared following a literature procedure. Up to now we have been able to isolate the dinuclear copper complex 8c using complex 9b while further improvements are still in progress for the synthesis of 3c and 4c. Copper and silver complexes have been tested in carbene and nitrene transfer reactions, C-N and C-O coupling reactions (Ullmann reaction) and C-C coupling reactions (Sonogashira reaction). Complex 1c exhibits an uncommon behaviour in Ullmann coupling. Commonly in this reaction aryl halides with electron donating substituents are less reactive than aryl halides bearing electron-withdrawing groups. In the case of complex 1c however, aryl halides bearing weakly electron-donating groups, such as methyl, give actually lower yields than aryl halides bearing strongly electron donating groups such as methoxy. In order to better understand the catalytic behaviour of complex 1c several tests have been run with complex 2c and with a reference monocarbenic copper(I) complex previously synthesized by Nolan. Complex IPrCuCl has been employed in the arylation of pyrazole, imidazole and 4-cresol and has shown an excellent catalytic activity even with aryl chlorides, in particular for the coupling reaction of 4-cresol. Complex 2c has been employed in the arylation of imidazole with aryl halides and has shown a good reactivity in this reaction. Both complexes 2c and IPrCuCl follows the classical trend as iodoanisole gives a yield lower than iodotoluene. The catalytic activity of complexes 1c, 2c and IPrCuCl has been also studied in the Sonogashira coupling of aryl halides and alkynes. IPrCuCl did not catalyse such reaction, but complexes 1c and 2c exhibit good activity with aryl iodides. Complex 1c gives quantitative yields with iodoacetophenone and also with iodotoluene while with the less reactive iodoanisole we obtain a yield of 54%. Silver-NHC complexes were tested in this reaction too; the best result was obtained with complex 6b in DMF; the other complexes give poor or no yield. Quite unexpectedly, by changing the solvent also the selectivity of the catalyst changes; running the reaction in DMSO the aryl-aryl coupling product was preferentially formed instead of the Sonogashira product. Some copper and silver complexes were employed also in carbene and nitrene tranfer reactions with respectively EDA and PhI=NTs as carbene and nitrene sources. Complex 8c has revealed a high catalytic activity and chemoselectivity in the cyclopropanation of styrene with ethyl diazoacetate and also a certain activity in the carbene insertion into the a-CH bond of THF. In nitrene transfer reaction complexes 1c and 8c exhibit high activity in the aziridination of styrene and complex 1c also gave a yield of 30% in the amination of toluene with PhI=NTs, whereas the best catalyst report to date for this reaction, which is a perbrominated trispyrazolylborate copper(I) complex, gives a yield of 60%. Silver-NHC complexes 6b and 7b were insoluble in dichloromethane, which was the solvent used for these reactions. In order to avoid solubility problems we tried to use the ionic liquid butyltrimethylammonium bis(trifluoromethylsulfonyl)imide as solvent, since complexes 6b and 7b were soluble in it, but unluckily these complexes were found to be inactive in carbene-transfer reactions. Another issue of this PhD project consists in the application as catalysts for ligand-free Sonogashira coupling reactions of copper species supported on inorganic supports such as silica, alumina and silica-alumina. These catalysts were prepared by Dr. Ravasio of ISTN-CNR of Milan trough chemisorption-hydrolysis method. The reaction examined was the coupling of phenyl acetylene with various aryl halides. We found that switching from silica to alumina-supported materials and also to the fully reduced material (Cu/Al) significantly increased the catalytic efficiency of the catalyst allowing to obtain an almost quantitative yield in the coupling of iodoacetophenone. Whereas deactivated aryl iodides turned out to be much more active in the presence of the pre-reduced Cu/Al; reactions with aryl bromides or chlorides gave poor yields with all the catalysts. Furthermore, determination of the conversion curve made it clear that exists an induction period, apparent from the sigmoidal shape of the curve, which suggests that CuO/Al acts in fact as a precatalyst generating the true catalytically active species in situ. In conclusion, the synthesis of new copper(I)-NHC complexes was quite complicated, however the synthetic pathway developed in collaboration with Santini and coworkers seems to be promisingly. We managed to isolate and characterisate two copper(I) complexes (2c and 8c) and we also obtain several tricarbenic trinuclear silver(I) complexes. Most of the complex prepared were tested as catalysts in C-C and C-Heteroatom forming reaction giving in some case significant results, to cite some: arylation of 4-cresol with chloroacetophenone catalysed by IPrCuCl and aziridination of styrene catalysed by complexes 1c and 8c.
Questo progetto di Dottorato riguarda la sintesi e la caratterizzazione di complessi di rame(I) e argento(I) con leganti policarbenici e il loro impiego come catalizzatori in reazioni di formazione di nuovi legami C-C e C-eteroatomo. É stata messa a punto una metodologia alternativa per la sintesi di complessi di rame(I) in collaborazione col gruppo del Prof. Santini dell’Università di Camerino. Questa metodica ha permesso di ottenere il complesso trinucleare di rame 2c, che ha una struttura trinucleare in cui ogni atomo di rame è coordinato a due anelli imidazolinidenici appartenenti a due unità tricarbeniche diverse. Il complesso 2c è stato preparato tramite una reazione di transmetallazione a partire dal complesso di argento 2b che è isostrutturale a 2c. La nuova procedura consente di ottenere 2c in basse rese tuttavia consente di ottenere dei complessi con purezza maggiore rispetto alla procedura classica. Il complesso 2c ha la stessa struttura del complesso 1c che è stato sintetizzato precedentemente all’inizio di questo progetto. Questo complesso è stato preparato seguendo la procedura classica di deprotonazione e differisce da 2c per la variata natura dei sostituenti agli atomi di azoto. L’applicabilità di questa procedura è stata poi investigate utilizzando altri complessi tricarbenici di argento preparati da Santini e anche ad alcuni complessi dicarbenici di argento preparati seguendo procedure di letteratura. Ad oggi è stato possibile isolare il complesso dinucleare di rame 8c utilizzando il complesso 9b come precursore, altri tentativi sono tuttora in corso per la sintesi dei complessi 3c e 4c. I complessi di rame e argento sono stati utilizzati nelle reazioni di trasferimento di carbeni e nitreni, nelle reazioni di coupling C-N e C-O (reazione di Ullmann) e di coupling C-C (reazione di Sonogashira ). Il complesso 1c mostra di avere un comportamento anomalo nella reazione di Ullmann. solitamente in queste reazioni gli alogenuri arilici con sostituenti elettron donatori sono meno reattivi di alogenuri arilici con sostituenti elettron attrattori. Nel caso del complesso 1c tuttavia, alogenuri arilici con sostituenti debolmente elettron donatori come il metile danno rese inferiori rispetto ad alogenuri arilici con sostituenti elettron donatori come il metossi. Per comprendere il comportamento del complesso 1c sono state condotte alcune reazioni di coupling col complesso 2c e on un complesso monocarbenico di rame(I) di riferimento che è stato sintetizzato da Nolan. Il complesso IPrCuCl è stato utilizzato come catalizzatore nelle reazioni di arilazione di imidazolo, pirazolo e 4-cresolo e ha mostrato di essere un buon catalizzatore, in particolare per il coupling di cloruri arilici. Il complesso 2c è stato impiegato nell’ arilazione di imidazolo con vari alogenuri arilici e ha dimostrato di avere una buona attività catalitica. IPrCuCl e 2c seguonol’andamento tipico di queste reazioni dato che la reazione con iodoanisolo da rese inferiori a quella con iodotoluene. L’attività catalitica dei complessi 1c, 2c e IPrCuCl è stata studiata anche per la reazione di Sonogashira per l’arilazione di alchini. IPrCuCl non catalizza questa reazione mentre i complessi 1c e 2c mostrano una buona attività catalitica con gli ioduri arilici. Il complesso 1c da rese quantitative con iodoacetofenone e iodotoluene mentre col meno reattivo iodoanisolo da una resa del 54%. Anche alcuni complessi di argento sono stati utilizzati in questa reazione, il risultato migliore è stato ottenuto col complesso 6b in DMF, gli altri complessi hanno dato rese basse o nulle. Sorprendentemente passando da DMF a DMSO cambia la selettività della reazione, infatti quando la reazione veniva condotta in DMSO si formava il prodotto di homocoupling dell’alogenuro arilico invece che l’arilalchino. Alcuni complessi di rame e argento sono stati impiegati come catalizzatori anche in reazioni di trasferimento di carbeni e nitreni utilizzando rispettivamente EDA e PhI=NTs come fonti di carbene e nitrene. Il complesso 8c si è rivelato cataliticamente attivo e selettivo nella reazione di ciclopropanazione di stirene con etildiazoacetato e ha dimostrato una certa attività catalitica anche nella reazione di funzionalizzazione di legame CH di THF. Nelle reazioni di trasferimento di nitreni i complessi 1c e 8c hanno dato rese elevate nella reazione di aziridinazione di stirene e il complesso 1c ha dato una resa del 30% nell’aminazione di toluene mentre il miglior catalizzatore per questa reazione (il complesso di rame con legante trispirazolilborato perbromato), ha dato una resa del 60%. I complessi di argento 6b e 7b sono insolubili nei più comuni solventi organici, per questo motivo si è deciso di utilizzare come solvente un liquido ionico commerciale, il butiltrimetilammonio bis(trifluorometilsolfonil)immide, dato che i complessi 6b e 7b sono completamente solubili nello stesso. Tuttavia anche in queste condizioni tali complessi non sono risultati cataliticamente attivi. Un’altra parte di questo progetto riguardava l’applicazione in catalisi di alcuni campioni di rame supportati su ossidi inorganici quali silice, allumina e silice-allumina. Questi catalizzatori sono stati preparati dal gruppo della Dottoressa Ravasio del ISTN-CNR di Milano attraverso il metodo di idrolisi-chemisorbimento. La reazione presa in esame è la reazione di Sonogashira Dai risultati emerge che in generale i materiali supportati su allumina sono più reattivi rispetto a quelli supportati su silice e che il catalizzatore di rame metallico da rese più elevate rispetto al catalizzatore contenente rame ossido. Dalla forma sigmoidale della curva di reazione appare evidente la presenza di un periodo di induzione. Questo suggerisce che le specie di rame supportato agiscano in realtà come precatalizzatore e che la specie cataliticamente attiva si formi direttamente nell’ambiente di reazione. Per concludere, la sintesi di nuovi complessi di rame con leganti carbenici è risultata complicata, tuttavia la nuova metodologia sviluppata in collaborazione con Santini sembra essere promettente. Due complessi policarbenici di rame sono stati ottenuti tramite questa metodologia (2c e 8c) e sono stati ottenuti anche alcuni complessi di argento. I complessi ottenuti sono stati applicati in catalisi in reazioni di formazione di legami C-C e C-eteroatomo. Alcuni dei risultati ottenuti sono molto interessanti: l’arilazione di 4-cresolo con cloroacetofenone catalizzata da IPrCuCl e aziridinazione di stirene catalizzata dai complessi 1c e 8c.

Thesis advisor: Amir H. Hoveyda
Chapter 1 Enantioselective Conjugate Additions of Carbon Nucleophiles to Activated Olefins: Preparation of Enantioenriched Compounds Containing All-Carbon Quaternary Stereogenic Centers. Methods for enantioselective conjugate addition of nucleophiles to activated olefins generating products containing all-carbon quaternary stereogenic centers are critically reviewed. Enantioselective conjugate addition has been shown to be a powerful and concise approach to construct carbon-carbon bonds to prepare compounds containing sterically hindered stereogenic centers and has seen great advances in the past several years. Owing to the difficult nature of additions to relatively unreactive conjugate acceptors, compared to additions generating tertiary stereogenic centers, and construction of a sterically-hindered bond, in many cases, new and active catalysts had to be developed. The review discusses the areas where significant advances have been made as well as current limitations and future outlook. Chapter 2 Development of New and Active Catalysts for Cu-Catalyzed Enantioselective Conjugate Addition of Alkyl- and Arylzinc Reagent. Through development of new chiral catalysts, we have found an active and enantiodiscriminating bidentate, sulfonate-containing NHC-Cu catalyst that effects enantioselective conjugate addition of alkyl- and arylzinc reagents on notoriously difficult trisubstituted cyclic enones. Products are prepared with high levels of selectivity and participate in a variety of further functionalizations. The enantioselective additions are efficient and practical, not requiring rigorously anhydrous or oxygen-free conditions. Chapter 3 Cu-Catalyzed Enantioselective Conjugate Addition of Alkyl- and Arylaluminum Reagents to Trisubstituted Enones. Outlined in this chapter is the first effective solution for Cu-catalyzed enantioselective addition of alkyl and aryl nucleophiles to trisubstituted cyclopentenones generating products bearing a β-all-carbon quaternary stereogenic center. Products are obtained in up to 97% yield and 99:1 er, only requiring 5 mol % of an in situ generated Cu-NHC catalyst. The methodology was highlighted as one of the key steps in the total synthesis of clavirolide C. Not only five-membered rings, but six- and seven-membered rings serve as proficient partners in the enantioselective process. Moreover, in cases for the enantioselective aryl addition, in situ prepared Me₂AlAr can be used without purification, filtration, or isolation, only requiring the corresponding aryl halides. The additions have also been extended to trisubstituted unsaturated lactones and chromones. Chapter 4 Cu-Catalyzed Enantioselective Conjugate Addition of Vinylaluminum Reagents to Cyclic Trisubstituted Enones. An enantioselective protocol for the formation of β,β-disubstituted cyclic ketones containing a synthetically versatile vinylsilane is disclosed. Enantioselective conjugate addition of in situ prepared silyl-substituted vinylaluminum reagents to β,β-unsaturated ketones promoted by 5 mol % of chiral Cu-NHC complexes delivers desired products with high efficiency (up to 95% yield after purification) and enantioselectivities (up to >98:<2 er). Several functionalizations utilizing the vinylsilanes, vicinal to an all-carbon quaternary stereogenic center, are shown, including an oxidative rearrangement, vinyl iodide formation and protodesilylation, accessing products not previously attainable. Furthermore, the enantioselective protocol is demonstrated as the key transformation in the total synthesis of riccardiphenol B
Thesis (PhD) — Boston College, 2011
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry

Les arylopeptoïdes (ou oligomères d’aminométhylbenzamides N-substitués) sont une classe d'oligoamides inspirés des peptoïdes et possédant un squelette aromatique. Ils conservent les caractéristiques intéressantes des peptoïdes telles que la synthèse par une approche submonomère et les préférences conformationnelles régies par l'isomérie cis-trans des amides N,N-disubstitués. Ces oligoamides aromatiques N-alkylés peuvent être développés en tant que protéomimétiques ou plateformes pour une présentation multivalente. L'objectif de cette thèse était d'explorer la diversité chimique accessible à partir des arylopeptoïdes linéaires et cycliques grâce à la chimie Click en utilisant un catalyseur de type carbène N-hétérocyclique de cuivre(I).Tout d'abord, l'accès et les propriétés du catalyseur N-carbène hétérocyclique de cuivre (I) sont exposés. Aussi, une application de la RMN quantitative est présentée pour obtenir la pureté de ce catalyseur (ainsi que d'autres composés organométalliques). Le développement d'un protocole CuAAC efficace sur résine utilisant ce catalyseur carbène cuivre pour la fonctionnalisation des arylopeptoïdes a permis la préparation efficace d'une bibliothèque d'oligomères linéaires portant plusieurs chaînes latérales de type triazole. Parallèlement, des approches combinatoire et séquentielle ont été mises en œuvre conduisant à une plus grande diversité chimique. La post-modification des triazoles en triazoliums a conduit à plusieurs séries d'arylopeptoïdes à base de triazolium présentant un caractère amphipathique. Leur activité antibactérienne a été évaluée sur un panel de souches bactériennes. L'accès par la réaction CuAAC à des structures tridimensionnelles en forme de couronne et/ou de tube à partir de macrocycles arylopeptoïdes contraints s'est également avéré efficace avec une sélectivité dépendant de la pré-organisation spatiale du macrocycle et du choix approprié du catalyseur. Enfin, l'accès à des arylopeptoïdes branchés en forme de H a été étudié en utilisant la réaction CuAAC sur résine. Dans l'ensemble, ce travail met en évidence le potentiel du catalyseur de type carbène cuivre (I) pour effectuer la poly-fonctionnalisation d’arylopeptoïdes sur résine et pour construire des architectures 3D complexes
Arylopeptoids (i.e. oligomeric N-substituted aminomethyl benzamides) is a class of peptoid-inspired oligoamides with aromatic backbone. They retain advantageous features of peptoids such as straightforward synthesis by submonomer approach and conformational preferences governed by cis-trans isomerism of N,N-disubstituted amides. These N-alkylated aromatic oligoamides may be developed as proteomimetics or scaffolds for multivalent display. The aim of this thesis was to explore the chemical diversity accessible from linear and cyclic arylopeptoids through Click chemistry using Copper carbene as catalyst. First, access and properties of Copper (I)-N-heterocyclic carbene catalyst was exposed. Also, an extension of the quantitative NMR was presented to study the purity of this catalyst and other organometallic compounds. The development of an efficient CuAAC protocol on-resin using Copper (I)-N-heterocyclic carbene catalyst for the functionalization of arylopeptoids has allowed the efficient preparation of a library of linear oligomers carrying several triazole-type side chains. Beside, combinatorial and sequential approaches have been implemented leading to huge accessible chemical diversity. Post-modification of the triazoles into triazoliums has led to several series of triazolium-based arylopeptoids exhibiting amphipathic character. Their antibacterial activity against a panel of bacterial strains has been evaluated. The access to 3-dimensional crown- and tube-like structures from constrained arylopeptoid macrocycles by CuAAC reaction using the Cu-NHC catalyst also proved to be efficient with a selectivity depending on the spatial preorganization of the cyclic core and proper choice of the NHC catalyst. Finally, the access to H-shaped arylopeptoids was studied using CuAAC reaction on resin. Overall, this work highlights the potential of the Copper (I)-N-heterocyclic carbene as catalyst for CuAAC to perform on-resin poly-functionalization of arylopeptoids and to build complex 3D-architectures

Thesis advisor: Amir H. Hoveyda
Chapter 1. A Review of Sulfonate-Containing NHC Ligands in Copper-Catalyzed Enantioselective Transformations—Maneuvering Selectivities in Tight Space. A comprehensive review of enantioselective copper-catalyzed transformations, which are promoted by a chiral N-heterocyclic carbene metal complex that features a unique sulfonate motif, is provided in this chapter. Reactions have been categorized into four sets: allylic substitutions conjugate additions, Cu-B additions alkenes and multicomponent reactions. The mechanistic scenarios provided by DFT calculations accounts for their uniquely reaction profile in enantioselective allylic substitutions (EAS), enantioselective conjugate additions (EAS) and enantioselective Cu-B additions to alkenes. Mechanistic investigations (density functional theory calculations and deuterium labeling) point to a bridging function for an alkali metal cation connecting the sulfonate anion and a substrate’ s phosphate group to form the branched addition products as the dominant isomers via Cu(III) π -allyl intermediate complexes in EAS reactions. Sulfonate-bearing NHC ligand with different substitution patterns promote EAS reactions with different reactivity and enantioselectivity. We also developed a guideline to follow to choose the proper sulfonate-based NHC ligands according to the combination of the substrates and the nucleophiles. Chapter 2. NHC–Cu-Catalyzed Enantioselective Allylic Substitutions with Silyl-protected Propargyl Boron Reagent to Generate Tertiary and Quaternary Carbon Stereogenic Centers. Catalytic allylic substitution reactions involving a propargylic nucleophilic component are presented; reactions are facilitated by 5.0 mol % of a catalyst derived from a chiral N-heterocyclic carbene (NHC) and a copper chloride salt. A silyl-containing propargylic organoboron compound, easily prepared in multi-gram quantities, serves as the reagent. Aryl- and heteroaryl-substituted disubstituted alkenes within allylic phosphates and those with an alkyl or a silyl group can be used. Functional groups typically sensitive to hard nucleophilic reagents are tolerated, particularly in the additions to disubstituted alkenes. Reactions may be performed on the corresponding trisubstituted alkenes, affording quaternary carbon stereogenic centers. Incorporation of the propargylic group is generally favored (vs allenyl addition; 89:11 to >98:2 selectivity); 1,5-enynes can be isolated in 75−90% yield, 87:13 to >98:2 SN2′:SN2 (branched/linear) selectivity and 83:17−99:1 enantiomeric ratio. Utility is showcased by conversion of the alkynyl group to other useful functional units. Application to stereoselective synthesis of the acyclic portion of antifungal agent plakinic acid A, containing two remotely positioned stereogenic centers, by sequential use of two different NHC–Cu-catalyzed enantioselective allylic substitution (EAS) reactions further highlights utility. Chapter 3. NHC–Cu-Catalyzed Enantioselective Allylic Substitutions with Methylenediboron to Generate Tertiary and Quaternary Carbon Stereogenic Centers. A catalytic EAS method for the site- and enantioselective addition of commercially available di-B(pin)-methane to disubstituted allylic phosphates is introduced. Transformations are facilitated by a sulfonate-containing NHC–Cu complex and products are obtained in 63–95% yield, 88:12 to >98:2 SN2’/SN2 selectivity, and 85:15–99:1 enantiomeric ratio. The utility of the approach is highlighted by its application to the formal synthesis of the cytotoxic natural product rhopaloic acid A, in an all-catalytic-method synthesis route. Catalytic EAS methods of the di-B(pin) methane to Z-trisubstituted allylic phosphates are also disclosed and DFT calculations provide insights to the stereochemical models for those transformations and rationales for the choice of Z-trisubstituted allylic phosphates as the starting materials. Chapter 4. Enantioselective NHC–Cu-Catalyzed Prenyl Conjugate Additions to Enoates to Generate Tertiary Carbon Stereogenic Centers. An efficient catalytic protocol for generation of prenyl-bearing tertiary carbon stereogenic centers from aryl-substituted enoates was achieved in the presence of a chiral alkoxy-based NHC–Cu complex. A range of aryl and heteroaryl-substituted substrate were suitable substrates, the corresponding prenyl conjugate addition products were generated in up to 94% yield and 95:5 enantioselectivity. The utility of the current method has been shown in the application to the synthesis of a selective integrin antagonist. DFT calculations provided a stereochemical model for the ECA reaction employing alkoxy-containing NHC–Cu catalyst
Thesis (PhD) — Boston College, 2017
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry

Thesis advisor: Amir H. Hoveyda
Formation of C-C bonds is an invaluable tool for the construction of materials, pharmaceuticals, natural products, and the building blocks of life. Although great strides in this area have been made, there remain several limitations in regio-, site-, and enantioselective additions of carbon-based nucleophiles. Solving these challenges by expanding the scope, efficiency, and selectivity of alkyl, aryl, heteroaryl, vinyl, and alkynyl additions to carbon-based electrophiles is the topic of this dissertation
Thesis (PhD) — Boston College, 2013
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry

Two types of research were carried out in this thesis; the first section is about the development of a new phosphine-based tridentate pincer N-heterocyclic carbene ligand and examination of the catalytic activities of its transition metal compexes including conjugated addition, alkyne-aldehyde addition and Alkyne-Aldehyde-Amine (A-3) coupling reaction. The second section of the thesis is about the methodology development of an A-3 based tandem synthesis of isoindoline derivatives and gold (I) catalyzed cyclization for the synthesis of isoindolo[2,1-a]quinolines derivatives. The aim of these studies is to develop novel catalysts and synthetic methodologies that can approach conventional chemical syntheses in a "greener" manner, therefore substantially gain atom-economy, step-economy and leads to a more sustainable life.
Deux types de recherches ont été accompli dans cette thèse. La première section comporte sur le développement d'un nouveau ligand carbène hétérocyclique et l'analyse de ses complexes formés avec des métaux de transitions et leur efficacité lors des additions conjuguées, d'addition alcyne-alcène et des réactions de couplage entre un alcyne, une aldéhyde et une amine (A-3). La deuxième partie de cette thèse porte sur le développement d'une méthodologie de synthèse de dérivés d'isoindoline utilisant une réaction en tandem dérivés du couplage A-3 et la synthèse de dérivés d' isoindolo[2,1-1]quinolines par cyclisation catalysée par des sels d'or(I). Le but de ces études étant de développer des méthodologies de synthèse et des catalyseurs novateurs pouvant s'appliquer à des synthèses conventionnelles et de ce fait les rendre plus "vertes", en augmentant leur économie d'atomes, économie d'étapes dans une perspective de développement durable.

Thesis advisor: Amir H. Hoveyda
Catalytic enantioselective reactions are of great importance in synthetic organic chemistry. Thus, development of efficient, selective and easily accessible catalyst for various bond formations is the main task in our laboratories. First, we have developed the first broadly applicable enantioselective boryl conjugate addition reactions to a variety of α,β-unsaturated carbonyls, promoted by a chiral Lewis basic N-heterocyclic carbene. The valuable β-boryl carbonyls were further used in complex molecule syntheses. The mechanism of these C–B bond formations was studied in details. We have also developed a practical method for enantioselective addition of an allene unit to aryl-, heteroaryl- and alkyl-substituted Boc-aldimines. These efficient C–C bond formations, catalyzed by an aminophenol-derived boron-based catalyst, were further utilized in succinct syntheses of anisomycin and epi-cytoxazone. Finally, chiral NHC–Cu complexes were employed for site-, diastereo- and enantioselective silyl conjugate additions to acyclic and cyclic dienones and dienoates. The precious enantiomerically enriched allylsilane obtained can be converted into a ketone-aldol type product, which is difficult to access through alternative methods
Thesis (PhD) — Boston College, 2015
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry

This thesis involves the preparation and exploration of the reactivity of a variety of organocopper complexes with N-heterocyclic carbene (NHC) ligands. The ligands contain either pyridyl/picolyl/allyl N-substituents or a xanthine-derived backbone. Structural modifications were made to the NHC ligands which were investigated for their catalytic activity when coordinated with Cu(I) in situ in an Ullmann-type etherification reaction. The ligand found to be the most active in catalysis was 1 allyl-3-picolylbenzimidazol-2-ylidene. The catalytic reaction was studied in more detail to assess deactivation pathways through reductive elimination of aryl imidazolium, dehalogenation and/or homocoupling of aryl iodide. In order to quantify the deactivation pathways, the preparation of novel aryl-imidazolium salts via C 2 selective arylation of imidazole, and of a biaryl via a Pd-catalysed was necessary, which led to more understanding the Cu-catalysed reaction and further side-reactions. The arylation of NHC-related species was exploited in the C 2 arylation of xanthine-derived compounds. The reactions were investigated via Cu NHC complexes, prepared using an electrochemical method. The kinetics of the arylation of a xanthine-derived Cu-NHC complex were studied using in situ 1H NMR and IR spectroscopies. Optimisation and a full understanding of this reaction has potential application in the detection of mismatched DNA bases. Further to the non-innocent behaviour of NHCs, an unusual Cu-mediated annulation reaction involving an allyl N-substituent was investigated. The reaction is proposed to occur via oxidative addition of C-Br to a Cu2Br2 cluster, Br migration and reductive elimination of the annulated product. Although most of the reactions discussed in this thesis are thought to proceed via a Cu(III) intermediate, the isolation of a Cu(III)-NHC has not been achieved to date. Attempts were therefore made to stabilise a Cu(III)-NHC using the macrocyclic effect, which may allow more understanding of the elusive Cu(III) NHC intermediate in a variety of reactions.

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.

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 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.

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, characterisation and reactivity of new manganese and rhenium(I) NHC complexes, which have been investigated both thermally and photochemically and the results contrasted with existing phosphine analogues in the literature. Cp’Mn(CO)2(NHC) (NHC = IEt2Me2 1, IMes 2, IiPr2Me2 3 and IPr 4) were synthesised and investigated by TRIR spectroscopy. Loss of CO was observed after 355 nm irradiation to form agostically stabilised intermediates, which reformed the parent species by recombination with CO on the nanosecond timescale. Loss of NHC was not observed, in contrast to Cp’Mn(CO)2(PPh3) which lost both CO and PPh3 upon photolysis. [Re(NHC)(Bpy)(CO)3]BAr4F (NHC = IEt2Me2 5, IMes 6) were synthesised and investigated by TRIR spectroscopy and UV/Vis absorption and emission spectrometry. Inclusion of an NHC altered the excited state manifold of the complexes, favouring population of the 3MLCT over the 3IL excited state. The lowest energy excited state for both 5 and 6 proved to be a 3MLCT excited state at 298 and 77 K. In contrast, [Re(PPh3)(Bpy)(CO)3]BAr4F exhibited 3MLCT at 298 K, but 3IL at 77 K. A series of complexes, M(NHC)(CO)4X and M(NHC)2(CO)3X (M = Re, X = Cl; M = Mn, X = Br) formed upon reaction of the corresponding M(CO)5X species and free NHC. The substitution pattern was dictated by the steric bulk of the NHC. Generation of the corresponding cations by halide abstraction was investigated. M(NHC)2(CO)3X was found to form agostic stabilised species upon halide abstraction by NaBAr4F in CH2Cl2. Under the same conditions, Re(IPr)(CO)4Cl was found to form the dichloromethane complex, [Re(IPr)(CO)4(η1-CH2Cl2)]BAr4F. In C6H5F solution under an atmosphere of dihydrogen, the CH2Cl2 ligand could be displaced by H2 to form the dihydrogen species, [Re(IPr)(CO)4(H2)]BAr4F.

Chapter one introduces N-heterocyclic carbenes (NHCs) and discusses their use as ligands for rare earth metal complexes, with particular emphasis upon compounds synthesised from 2009 until the present day. Chapter two details the synthesis and characterisation of the homoleptic scandium-NHC complex [Sc(L)3] (L = [OCMe2CH2(1-C{NCHCHNiPr})]). Reactions of [Sc(L)3] with boranes, CO2 and CS2 are described which exploit the relative lability of the Sc–Ccarbene bond and allow formation of [Sc(L)2(OCMe2CH2(1-B'C{NCHCHNiPr}))] (B' = 9-BBN, BPh3, B(C6F5)3, BH3), [Sc(OCMe2CH2(1-O2CC{NCHCHNiPr})3]n, [Sc(L)2(OCMe2CH2 (1-S2CC{NCHCHNiPr})] and [Sc(L)(OCMe2CH2(1-S2CC{NCHCHNiPr})2]2. The chapter also discusses the reactivity of [Sc(L)3] towards substrates containing acidic C–H and N–H bonds and substrates containing polar E–X bonds (where E = C, Si, B, P and X = Cl, I). Chapter three describes the synthesis and characterisation of the NHC substituted scandium benzyl complexes [Sc(Bn)2(L)]2 and [Sc(Bn)(L)2], and the attempted synthesis of NHC substituted scandium aminobenzyl complexes. The reactivity of [Sc(Bn)2(L)]2 with RX substrates (R = alkyl) is discussed in detail; depending on the nature of the alkyl group, these reactions can allow formation of R–Bn , the result of carbon-carbon coupling. The complex [Sc(Bn)(L)Cl]2 has been isolated from these reactions and is structurally characterised. The reactivity of [Sc(Bn)2(L)]2 towards C–H bonds is explored and attempts to prepare NHC substituted scandium hydrides are described. Comparisons of the relative stability and reactivity of [Sc(Bn)2(L)]2 and [Sc(Bn)3(thf)3] are drawn. Chapter four documents the synthesis and characterisation of [Sc(Odtbp)2(L)] (Odtbp = 2,6-di-tert-butylphenoxide), [Sc(Odtbp)(L)2], and the samarium analogue [Sm(Odtbp)(L)2]. The reactivity of these complexes towards various small molecules is described. The chapter also details attempts to prepare the cationic scandium complexes [Sc(L)2][Bort] (Bort = bis[3,3',5,5'-tetra-(tert-butyl)-2,2-diphenolato]borate) and [Sc(L)2][B(Ph)4]. Chapter five provides overall conclusions to the work presented in this thesis. Chapter six contains all experimental and characterising data for the complexes and reactions detailed in this work.

Récemment, les carbènes N-hétérocycliques (NHC) ont suscité un intérêt important dans le domaine de la chimie des matériaux. En effet, cette nouvelle catégorie de ligands forme des liaisons très fortes avec une diversité de métaux et leur structure, ainsi que leurs propriétés électroniques, peuvent être adaptées par de la synthèse organique. Cette forte liaison est d’un intérêt particulier dans le domaine des nanoparticules d’or (NP) et des synthèses ont déjà été proposées. En effet, les NPs présentent de nombreuses applications potentielles, par exemple dans les capteurs, en catalyse ou médecine, mais ces applications sont parfois freinées par un manque de stabilité du ligand de surface. Ce travail de thèse s’est concentré sur le développement de nouvelles synthèses de nanoparticules d’or stabilisées par des NHC. D’abord, en revisitant une procédure existante à base de sels d’imidazoliums, ce qui a mené à une synthèse n’utilisant que les composés commerciaux : AuCl et NaBH4 et des halogénures d’imidazolium, facilement obtenus. Une synthèse totalement nouvelle a ensuite été développée en utilisant des NHC-boranes qui sont des adduits de Lewis stables. Nous avons montré pour la première fois que les NHC-boranes peuvent être utilisés comme réactifs "2-en-1" dans la synthèse de NP : comme réducteurs du précurseur d’or et comme source de NHC. Enfin, nous sommes les premiers à décrire la synthèse de NP stabilisées par des carbènes mésoioniques (MIC).Les MICs sont une sous-catégorie des NHCs qui sont préparés par « chimie click » et qui présentent des propriétés électroniques uniques. Un intérêt particulier a été porté à la caractérisation des nanoparticules, notamment par XPS
Over the past decade, N-heterocyclic carbenes (NHC) have drawn considerable interest in the field of materials chemistry. Indeed, this relatively new class of ligands forms strong bonds with a wide range of metals and their structures and electronic properties can be tuned “at-will” through organic synthesis. This strong bond is of particular interest for gold nanoparticles. Indeed, gold nanoparticles have many potential applications, for example in sensors, catalysis or medicine, but those potential applications are sometimes hindered by a lack of stability of the surface ligand. A few syntheses of NHC-stabilized gold nanoparticles have already been described in the literature but each presents their own set of drawbacks. This thesis work has focused on the development of new syntheses of NHC-stabilized gold nanoparticles. First, by revisiting a literature procedure starting from imidazolium salts, we managed to develop a one-pot synthesis starting only from commercially available AuCl, NaBH4 and easily synthesized imidazolium salts. A totally new synthesis was developed using NHC-boranes, which are stable Lewis adducts. Here, we reported for the first time their use as a 2-in-1 reagent, able to reduce the metallic precursor and provide the nanoparticles stabilizing ligands. Finally, we are the first to report a synthesis of gold nanoparticles stabilized by mesoionic carbenes (MIC). MICs are a sub-class of NHCs synthesized by well-known “click-chemistry”, which present unique electronic properties. Throughout this work, special care was taken to characterize the nanoparticles, notably by XPS

The central focus of this study was the synthesis, structural investigation and characterisation of multiple chromium carbene complexes. Fifteen novel chromium(0) complexes were synthesised. The synthesis of the primary monocarbene starting material [Cr(CO)5{C(OEt)(heteroaryl)}], heteroaryl = thiophene, furan, 2,2’-bithiophene, was carried out utilising typical Fischer methodology. A wide variation of spacer ligands were reacted to obtain different carbene substituents. The ligand substitution reaction between carbonyl ligands and the bidentate ligands followed the techniques proposed in literature and produced distinctive chelated monocarbene complexes with the resulting structure mer- [Cr(CO)3(dppe){carbene)}]. An extensive collection of more sophisticated monocarbene complexes was synthesised via modification pathways (aminolysis). Conversion of original ethoxy-bearing monocarbenes through aminolysis provided the corresponding amine analogues, possessing both novel structure and unique chemical reactivity. The aminolysis reactions involved different sized amino reagents; both ammonia and cyclohexyl amine (bulky, cyclic chair amines) were employed to produce derivatives of the monocarbene starting complexes. Lastly, the synthesis of unique N-heterocyclic carbene (NHC) complexes was envisaged. Synthesis of both the pentacarbonyl-bearing and phosphine-bearing NHC complexes was attempted utilising an adapted version of a methodology proposed in literature. The synthesis of chelate NHC complexes, however, proved difficult and the resulting products were not obtained. All Fischer and N-heterocyclic carbene complexes were characterised using infrared spectroscopy, nuclear magnetic resonance spectroscopy and mass spectrometry. In cases where single crystals were obtained, X-ray crystallography was used to confirm molecular structures. X-ray crystallographic studies indicated that carbonyl substitution reactions performed on monocarbene starting material, will favour the formation of the meridonial isomer in molecules where the carbene substituents are less bulky. Due to steric considerations, the substitution of labile carbonyl ligands in the trans position to the carbene moiety will be favoured. Density functional theory (DFT) calculations were performed on the complexes synthesised in this study. The results obtained indicated the favoured isomeric form to be facial in some cases whereas crystallographic data signified the meridonial isomer as the more stable product, irrespective of the bulkiness of the carbene substituents. Bond lengths, geometry and bond angles were all comparable to those of the single-crystal X-ray data. Single-point energy calculations show clearly that modelling methods provide good estimations of energetically favourable geometries, and accurate DFT calculations also predict the HOMO and LUMO orientations around the metal or ligand spheres. The majority of the structures provided by the computed model, illustrated that the 3d atomic orbitals of the metal contributed significantly to the HOMO, whereas the LUMO was mostly orientated around the carbene carbon atom. Metathesis and polymerisation catalytic reactions were attempted on [Cr(CO)3(dppe){C(OEt)(thiophene)}], 2, whereas only metathesis studies were employed for [Cr(CO)3(dppe){C(NHCy)(thiophene)}], 6. Both complexes presented as inert to either reaction and no catalytic capability was witnessed. Gas chromatography was used to indicate the level of progression of the reaction and the chromatogram verified that neither pre-catalyst found application in metathesis or, in the case of 2, in polymerisation.
Dissertation (MSc)--University of Pretoria, 2012.
Chemistry
MSc
Unrestricted

The synthesis of novel Fischer and N-heterocyclic tungsten(0) carbene complexes was endeavoured in this study and resulted in the synthesis, isolation and characterisation of eighteen new complexes. Sixteen novel Fischer carbene complexes were synthesised. In these complexes, both carbene ligand substituents were varied. Ethoxy as well as amino heteroatom substituents were used. Heteroaryl compounds thiophene and furan were employed as the second substituents on the carbene ligand. Complexes with combinations of these different substituents were synthesised and investigated to assess the influence the various substituents of the carbene ligand may have on the carbene complex itself. In addition, the metal ligand sphere was altered by substitution of one or two carbonyl ligands for either an amine or a phosphine ligand/s. These substitutions resulted in the formation of metal pentacarbonyl, metal tetracarbonyl as well as metal tricarbonyl systems. The complexes were successfully characterised by means of NMR and IR spectroscopy, and in selected cases X-ray diffraction and mass spectrometry. Synthesis of N-heterocyclic carbene complexes derived from isopropyl and mesityl imidazolium chlorides was attempted. The products were obtained in crude form, but could not be isolated due to decomposition during purification. Two novel decomposition products, which point towards a unique decomposition route, were isolated. Theoretical models of both the novel Fischer carbene complexes and the N-heterocyclic carbene complexes were calculated. This allowed for identification of infrared modes observed in experimental data. Furthermore, the HOMO and LUMO distributions and the HOMO-LUMO energy gaps were calculated, along with electrostatic potential maps. In all the Fischer carbene complexes the HOMOs were located on the metal centre and the LUMOs on the carbene ligand. In contrast, the HOMO and the LUMO were both located on the metal centre for the N-heterocyclic carbenes. The HOMO-LUMO energy gap decreased as follows: NHC complexes > Amino Fischer carbene complexes > Ethoxy Fischer carbene complexes Lastly, in all the complexes studied, the electrostatic potential maps indicated that the highest amount of electron density was found on the carbonyl ligands of these complexes. Both experimental and theoretical data indicated marked differences in the various classes of compounds, suggesting that these complexes would not only have different reactivities but also be suited to different applications. Experimental studies on reactivity and applications are thus future avenues of study which are made available from these results.
Dissertation (MSc)--University of Pretoria, 2012.
Chemistry
MSc
Unrestricted

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

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

The versatility of N-heterocyclic carbenes (NHCs) is demonstrated by numerous practical applications in homogeneous transition metal catalysis, organocatalysis and materials science. There remains a paucity of electropositive metal NHC complexes and so this chemistry is poorly developed with respect to that of the late transition metal and main group elements. This thesis describes the synthesis of new alkoxy-tethered NHC proligands, their use in the synthesis of reactive metal amide and metal alkyl complexes, and finally small molecule activation using these complexes. Chapter One introduces NHCs and discusses their use as supporting ligands for early transition metal and f-block complexes. Small molecule activation using organometallic complexes is examined alongside the use of electropositive metal NHC complexes in catalysis. Chapter Two contains the synthesis and characterisation of new alkoxy-tethered NHC proligands and a variety of electropositive MII (M = Mg and Zn), MIII (M = Y, Sc, Ce and U) and MIV (M = Ce and U) amide complexes. X-ray diffraction studies and a DFT study are used to probe the extent of covalency in the bonding of the MIV complexes. Chapter Three investigates the reactivity of the amide complexes prepared in Chapter Two. The MII complexes are shown to be initiators for the polymerisation of raclactide into biodegradable polymers. The MIII complexes are used to demonstrate additionelimination reactivity of polar substrates across the M-Ccarbene bond which allows the formation of new N-E (E = Si, Sn, P or B) bonds. Treatment of the UIII silylamide complex U(N{SiMe3}2)3 with CO results in the reductive coupling and homologation of CO to form an ynediolate core -OC≡CO- and the first example of subsequent reactivity of the ynediolate group. The MIV complexes are used to examine the potential for forming MIV cationic species and alkyl complexes. Chapter Four examines the synthesis of MIII (M = Ce and Sc) aminobenzyl complexes and MIII (M = Y, Sc and U) neosilyl and neopentyl alkyl complexes. The addition-elimination reactivity discussed in Chapter Three is extended to include C-E bond formation (E = Si, Sn, P, B, I or C). Chapter Five provides overall conclusions to the work presented within this thesis. Chapter Six gives experimental and characterising data for all complexes and reactions in this work.

Ligands involving CNC structures have been of intense interest in research. With an aim to investigating this area, a modular synthesis was developed using condensation reactions between a base unit of 2,6-dichloroisonicotinic acid and N-alkyl imidazoles toprovide a range of 2,6-bis(imidazolium) salts. From this point several methods wereavailable to incorporate an active metal centre, however, state of the art microwaveaccelerated synthesis was found to be the most successful technique in forming the tridentate palladium complexes. Several strategies were investigated to attach these complexes to polymer resins, exploring a range of linking groups, coupling procedures and resins. The most effective strategy involved forming an acid functionalised palladium complex to allow loading onto an amino-functionalised resin. Although several reagents were investigated it was found that the commercially available reagent PyBop® was the most effective in forming the stable amide bond from the palladium complex to the polymer resin. By using an excess of coupling reagent and an excess of the acid functionalised palladium complex complete loading onto an amino functionalised resin could be achieved.The supported complexes were found to be highly stable catalysts in Heck, SuzukiMiyauraand Stille reactions, and capable of cross-coupling a range of aryl iodides in very high yields. The active catalysts showed very little leaching of palladium (ICPMS) and could be recycled up to fourteen times with no loss of activity. Long reaction times were overcome using tetra-n-butylammonium bromide as an additive or by using microwave irradiation. Following these catalytic studies and with an aim to using less active electrophiles, several strategies were investigated to develop enhanced activity catalysts. These strategies involved replacing one of the N-Heterocyclic carbene ligands with either an "inert" bulky group or with another alternative ligand. Full details of this research are presented in chapters 2 to 5.