Дисертації з теми "N-N bonds"

The formation of C-C and C-N bonds in modern organic synthesis is a key target for methodological advancement. Current methods of C-C and C-N bond formation often involve the use of expensive catalysts, or sub-stoichiometric reagents, which can lead to the generation of undesirable waste products. This thesis describes a novel and environmentally benign set of reaction conditions for the formation of C-C and C-N bonds by hydroacylation and this is promoted by mixing two reagents, an aldehyde and an electron-deficient double bond, under freely available atmospheric oxygen at room temperature Chapter 1 will provide an introduction to the thesis and mainly discusses methods for C-C bond formation, in particular, radical chemistry and hydroacylation. Chapter 2 describes the hydroacylation of vinyl sulfonates and vinyl sulfones (C-C double bonds) with aliphatic and aromatic aldehydes with a discussion and evidence for the mechanism of the transformation. Chapter 3 details the synthesis of precursors for intramolecular cyclisations and studies into aerobic intramolecular cyclisations. Chapter 4 describes the hydroacylation of vinyl phosphonates (C-C double bonds) and diazocarboxylates (N-N double bonds) with aliphatic and aromatic aldehydes bearing functional groups. In addition, the hydroacylation of diazocarboxylates with chiral aldehydes will be discussed. In conclusion, a new, facile and clean set of reaction conditions for the formation of C-C and C-N bonds has been developed via aerobic C-H activation of aldehydes providing access to unsymmetrical ketones.

Thesis (MComm)--Stellenbosch University, 2001.
ENGLISH ABSTRACT: In this study, the income tax implications of the acquisition of a debenture at a discount is investigated. The purpose of this study is determine whether the proceeds from the redemption or disposal of the above-mentioned debenture are of a revenue or capital nature. It is customary for companies to issue debentures in order to obtain long term finance. These debentures may be issued at a discount. There exists a general uncertainty in the academic literature regarding the income tax implications of the acquisition of a debenture at a discount to the face value thereof. Section 24J of the Income Tax Act includes a discount in the definition of "interest". There is no general definition of the words "interest" and "discount" in the Income Tax Act. The lack of a statutory definition of these words contributes to the uncertainty regarding the income tax treatment of the sale or redemption of a debenture. The following aspects are discussed: (a) the revenue or capital nature of the proceeds on redemption and transfer of a debenture; (b) the provisions of section 24J of the Income Tax Act; and (c) the provisions of capital gains tax. In order to determine the revenue or capital nature of the proceeds on redemption or transfer of a debenture, the following aspects are discussed: • The attributes of a debenture from an economic and legal perspective. The factors that determine the value of the discount of a debenture are considered from an economic viewpoint. • The guidelines that apply in general to determine the revenue or capital nature of accruals are considered with specific reference to the guidelines laid down by the South African courts. A distinction is drawn between the guidelines that consider the intention of the taxpayer and those guidelines that operate independently of the intention of the taxpayer. • The general guidelines are then applied to the proceeds on redemption or transfer of a debenture. The ordinary meaning of interest and the meaning of the interest in the Income Tax Act are considered. The relation between a discount and interest is examined. Case law from England, Australia and Canada are also considered. The writer comes to the conclusion that a discount that realises on redemption of a debenture is in the nature of interest. The discount is revenue derived from capital productively employed and therefore not of a capital nature. The proceeds from the transfer of a debenture is not of a capital nature if it is a gain made by an operation of business in carrying out a scheme for profit making. The writer is of the opinion that section 24J influences the application of the general principles. The writer is of the opinion that the objective test should be applied to determine the nature of the accrual amount in terms of section 24J. The accrual amount will include a proportional amount of the discount. The objective test should be applied irrespective of whether the debenture is held until redemption or transferred before redemption. The provisions of section 24J should be applied before the capital gain or capital loss is determined in terms of the Eight Schedule to the Income Tax Act. The proceeds from disposal must be reduced by any amount of the proceeds that was included in gross income or taken into account in determining the taxable income of a person. The base cost of a debenture acquired at a premium must be reduced by the amount of the premium that was allowed as a deduction in determining the taxable income of the holder of a debenture.
AFRIKAANSE OPSOMMING: In hierdie studie word die inkomstebelastinggevolge van die verkryging van 'n skuldbrief teen 'n diskonto ondersoek. Die doel van hierdie studie is am te bepaal of die opbrengs met die aflossing en verkoop van sodanige skuldbrief van 'n inkomste- of kapitale aard is. Een van die gebruiklikste metodes vir 'n maatskappy am langtermynleningsfondse te bekom, is deur die uitreiking van skuldbriewe. Skuldbriewe kan teen 'n diskonto uitgereik word. Daar bestaan "n algemene onsekerheid in die beskikbare literatuur met betrekking tot die inkomstebelastinggevolge van "n skuldbrief wat teen "n diskonto verkry is. Artikel 24J van die Inkomstebelastingwet sluit spesifiek 'n diskonto by die omskrywing van "rente" in. Die Inkomstebe/astingwet bevat egter nie 'n algemene omskrywing van die woorde "rente" en "diskonto" nie. Die gebrek aan 'n statutere omskrywing van bogenoemde woorde dra by tot die onsekerheid van die inkomstebelastinggevolge van die aflossing of verkoop van 'n skuldbrief. Die skrywer oorweeg die volgende: (a) die inkomste- of kapitale aard van die opbrengs met aflossing en verkoop van "n skuldbrief; (b) die bepalings van artikel 24J van die Inkomstebelastingwet; en (c) die bepalings van die kapitaalwinsbelasting-wetgewing. Ten einde die inkomste- of kapitale aard van die opbrengs met aflossing en verkoop van 'n skuldbrief te bepaal, word die volgende aspekte bespreek: • Die eienskappe van 'n skuldbrief vanuit "n ekonomiese- en regsoogpunt. Die faktore wat die waarde van die diskonto van "n skuldbrief be'invloed, word vanuit In ekonomiese oogpunt oorweeg. • Die riglyne wat algemeen ter sprake is by die bepaling van die inkomste- of kapitale aard van toevallings. Daar word spesifiek na die riglyne soos deur die Suid-Afrikaanse geregshowe neergele, verwys. In Onderskeid word kortliks getref tussen die riglyne wat vereis dat In belastingpligtige se doel met betrekking tot In bate vasgestel word en daardie riglyne wat onafhanklik van In belastingpligtige se doel toegepas word, • Die algemene riglyne word op die opbrengs met aflossing en verkoop van In skuldbrief toegepas. Die gewone betekenis van rente asook die betekenis van rente ingevolge die Inkomstebelastingwet word oorweeg. Die verband tussen In diskonto en rente word ondersoek. Engelse, Australiese en Kanadese regspraak word oorweeg. Die skrywer kom tot die gevolgtrekking dat In diskonto wat met die aflossing van In skuldbrief realiseer, rente van aard is. In Diskonto wat met aflossing realiseer is In bedrag voortgebring deur kapitaal produktief aan te wend en dus nie van In kapitale aard nie. In Opbrengs met die oordrag van In skuldbrief is nie van In kapitale aard nie indien dit verkry is uit die beoefening van In besigheidshandeling in die uitvoering van In skema van winsbejag. Die skrywer is van mening dat artikel 24J die toepassing van die algemene riglyne be'invloed. Die skrywer is van mening dat die objektiewe riglyn toegepas moet word am die aard van toevallingsbedrae soos ingevolge. artikel 24J bereken vas te stel. In Toevallingsbedrag sluit In proporsionele gedeelte van In diskonto in. Die objektiewe riglyn moet toegepas word ongeag of 'n skuldbrief tot op die aflosdatum gehou word of daarvoor oorgedra word. Die bepalings van artikel 24J moet toegepas word voordat die kapitaalwins of - verlies ingevolge die Agtste Bylae bereken word. Die opbrengs moet verminder word met enige bedrag wat by bruto inkomste ingesluit word of in ag geneem word by die vasstelling van belasbare inkomste. Die basiskoste van 'n skuldbrief wat teen 'n premie verkry is moet aangepas word met die bedrag van die premie wat reeds in ag geneem is am die belasbare inkomste van die houer van 'n skuldbrief te bepaal.

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.

The asymmetric reduction of imino bonds is a well known and utilised method of chiral amine synthesis. Chapter 1 gives an insight into the published methods for a range of substrates via hydrogenation and transfer hydrogention systems. This thesis presents a range of novel iridicycles, all of which contain chiral oxazoline and imidazoline ligands. The synthesised complexes demonstrate a variety of electronic and steric properties. Their activities are presented in the latter chapters for the asymmetric reduction of C=N bonds. Chapter 3 demonstrates the activity of the 4,5,6-trimethoxyimidazoline iridium complex for direct asymmetric reductive amination. High activity, yielding up to quantitative product is reported, under unusually mild conditions, in both aqueous and organic solvent systems. The enantioselectivites achieved were moderate to high for the substrates screened. The use of a bulky 2,4,6-tri-iso-propyloxazoline iridium complex is reported for the asymmetric reduction of quinolines, via transfer hydrogenation conditions. The tetrahydroquinolines were produced in high yields and moderate enantioselectivities. The addition of co-solvents to the aqueous system yielded improved enantioselectivies and conversions. For the reduction of pyridinium salts a bromo-dioxole imidazoline iridium complex presented high activity. This presents unprecedentedly mild conditions via a transfer hydrogenation system, producing high yields of N-benzyl piperidines. The enantioselectivites determined were high, although some could not be measured by the available means. The 2,4,6-tri-iso-propyloxazoline iridium complex further demonstrates high activity and enantioselectivity for the asymmetric hydrogenation of acyclic imines. An NMR and mechanistic study revealed the in-situ formation of a new iridium species present only in TFE.

The development of methods to construct new chemical bonds efficiently and selectively whilst minimising energy usage and waste production is of high importance in organic chemistry. Many current methods employ inefficient, costly and often toxic multi step protocols to generate new chemical bonds. The hydroacylation reaction is one method of reducing such inefficiencies. The development of an aerobic hydroacylation protocol in the Caddick group has recently allowed the functionalisation of aldehydes with a wide array of electron deficient alkenes. This process relies on trapping an acyl radical intermediate, from the auto-oxidation of aldehydes to acids, with a suitable alkene. Since aldehyde auto-oxidation takes place readily in the presence of atmospheric oxygen, the aerobic hydroacylation reaction can be conducted in aqueous media in the absence of any additional reagents. Following on from previous work in the group, this thesis describes studies towards expanding the scope of this novel methodology in the formation of C-N bonds. It also assesses the scalability of this reaction in order to make acyl hydrazides for further chemical transformations; as such, the development of protocols for the conversion of acyl hydrazides to carboxylic acid derivatives and to ketones will also be described. Chapter 1 provides an introduction to and a general overview of current methods of hydroacylation and acid derivative syntheses. Chapter 2 describes the development of conditions for, and application of aerobic hydroacylation towards C N bond formation, and the scalability of the hydroacylation reaction. Chapter 3 will focus on solving the failures of previous attempts for the conversion of acyl hydrazides to tertiary amides. Chapter 4 will demonstrate the applicability of acyl hydrazides to the synthesis of carboxylic esters and describe some of its limitations. Finally, chapter 5 will reveal acyl hydrazides as a new class of precursors for the chemoselective synthesis of ketones.

The origins of these investigations are in the pursuit of heterocycles containing an N-O bond. This project as a whole focusses on developing earlier chance observations made by previous members of the Knight Research Group. Chapter 2 focusses on the synthesis of isoxazoles: 5-membered aromatic rings containing a nitrogen to oxygen bond. The origin of this project was the unexpected observation of a small percentage of isoxazole products in the Group’s earlier synthesis of isoxazolines, which were thought to be the oxidation products arising from using silver nitrate as a catalyst for those cyclisations. It has now been found that by using an excess of silver nitrate, isoxazoles can be selectively formed from the same hydroxylamine precursors. Chapter 3 centres on the viability of obtaining unusual 6-endo-trig products from the iodocyclisation of unsaturated tert-butyl carbonates. This Chapter is connected to the theme of N-O chemistry, as the tert-butyl carbonate starting materials were the unexpected products of a synthesis that had been designed to form hydroxylamines. The initial discovery of these unexpected 6-endo products on iodocyclisation was expanded upon to produce a series of cyclic carbonates with a procedure optimised to maximise the yield of this desired structural isomer. Chapter 4 concentrates on building saturated N-O rings onto existing cyclic systems, including transannular cyclisations - investigating previous reports of rearrangement of N and O during cyclisation and working towards a synthesis of the core-structure of the natural product Histrionicotoxin. These schemes prove the utility of this acid-catalysed hydroamination methodology in building heterocycles and the chiral products that can be gleaned from them. For the most part, this project has been concerned with methodology - solving problems and optimising key-step procedures - which can be applied to complex target molecules.

Amines are ubiquitous in nature and serve a variety of functions in living organisms. Because of this fact amines are of great biological and pharmaceutical interest. The iridium catalyst (pentamethylcyclopentadienyl) iridium dichloride dimer ([Cp*IrCl2]2) has been used in a number of ways to synthesize new carbon-nitrogen bonds. These studies were directed toward the development of a method for the iridium catalyzed N-alkylation of alpha-amino acid esters as well as the development of a strategy for synthesis of the natural product 275A. We have optimized a method for the N-alkylation for alpha-amino acid esters. Using this method, we have N-alkylated a series of alpha-amino acid esters with a variety of alcohols. We have shown that the N-alkylation of the alpha-amino acid esters works consistently and gives the desired products in moderate to high yields. We have examined the effect of this method on the chiral center of the obtained products by analyzing their optical rotation. Evaluation of these specific rotations indicated racemization was occurring but it is believed that any loss of the chiral center is due to the reaction conditions. Amphibian alkaloids are of great interest to the pharmaceutical and academic communities due to their biological activities. Unfortunately, they are not naturally available in large quantities which makes total synthesis the most common method of generating these compounds for evaluation. One amphibian alkaloid class of interest to us are the Lehmizidines. These are bicyclic ring structures consisting of a 7-member and 5-member ring with a nitrogen bridgehead. The alkaloid, 275A, was selected as a target for a general synthetic approach. This synthetic approach required the synthesis of novel diols. The construction of these diols along with a method for the synthesis of the azepane ring is presented here.

Au cours de ce travail de nouvelles méthodes pour la formation de liaison C-N ont été développées. Dans la première partie de cette thèse une application de catalyse métal-ligand bifonctionnelle pour la réaction énantiosélective aza-Michael est démontrée. Dans la deuxième partie nous présentons le travail sur les cyclisations, en utilisant des alcaloïdes du quinquina facilement disponibles, comme catalyseurs des plus prometteurs, fournissant des β-amino-acides d’indoline avec jusqu'à 98% ee. Parmi eux, l’hydroquinidine ressort du lot comme étant le catalyseur donnant le meilleur excès énatiomérique. La troisième partie est liée à l'élaboration d'un nouveau processus intermoléculaires de diamination de styrènes, diènes et triènes, utilisant des bis-sulfonylimides comme source d'azote, en combinaison avec le diacétate de iodosobenzène, qui fournit une approche intéressante et efficace de diamines vicinales biologiquement et chimiquement important. La réaction peut être effectuée à température ambiante sans avoir besoin de protection par atmosphère inerte
The concept of metal-ligand bifunctionality was successfully applied for an enantioselective aza-Michael reaction by employing well-defined ruthenium amido complexes. The catalyst was optimised and the corresponding chiral indoline β-amino acid derivatives were obtained with high enantioselectivities. Next, a straightforward enantioselective bifunctional organocatalytic approach was also developed. Employing hydroquinidine as catalyst the corresponding cyclic products were obtained in excellent enantioselectivities and quantitative yields. These compounds can be selectively deprotected and applied to peptide synthesis. Finally, we have developed unprecedented diamination reactions of styrenes, butadienes and hexatrienes employing easily accessible hypervalent iodine(III) reagents under robust reaction conditions. The first examples of the metal-free 1,2-diamination of butadienes were demonstrated and this oxidation methodology was further extended to the highly attractive 1,4 installation of two nitrogen atoms within a single step

The regioselective activation of C-H bonds and subsequent transformation into desirable functional groupS is an attractive prospect in organic synthesis. We have developed two novel C-H functionalisation reactions; the first is an intramolecular, sulfonamide directed, C-H amination reaction for the synthesis of 3_phenylisoindolinone derivates and the second is a sulfonamide directed ortho C-H acetoxylation reaction. Both isoindolinones and phenol derivatives of sulfonamides are important motifs in numerous pharmaceutically relevant compounds. The Cull-catalysed intramolecular C-H amination reaction for the synthesis of substituted 3-phenylisolindolinone derivatives (Scheme i) was found to be tolerant to substitution on both aromatic rings, however, no reaction was observed on exchanging the tethered aryl group for an alkyl group. Mechanistic investigations revealed that C-H cleavage was not part of the rate-determining step which is likely to be coordination of the copper catalyst to the sulfonyl amide. Substitution of the tethered phenyl ring (R2 ) and a subsequent Hammett analysis indicated that this coordination may be accelerated by a cation-IT interaction between CU11 and the pie system of the aryl group.

The oxidative addition of the N-H bond of both heterocyclic and acyclic amines and the O-H bond of phenols, water and carboxylic acids to iridium(I) trimethylphosphines complexes was studied and the reactivity of the resulting hydrido amido-, aryloxo- and carboxylato iridium(III) complexes was investigated. Oxidative addition of the N-H bond of pyrrole, indole, 3-methylindole, 7-azaindole, carbazole and aniline to [Ir(COD)(PMe₃)₃]CI (1a) (COD = 1,5-cyclooctadiene) produces merIr( NR₂)H(PMe₃)₃CI (2a-f) complexes. That these amines were bound to iridium through an Ir-N bond was established by ¹H, ³¹P and ¹³C NMR spectroscopy, IR spectroscopy, C-H analyses and single crystal x-ray diffraction. Similarly, oxidative addition of the O-H bond of phenol, p-cresol, 3,5-dimethylphenol, and water to [Ir(COD)(PMe₃)₃]CI (la) produces mer-Ir(OR)H(PMe₃)₃C1 (5a-c and 6) which were characterized by ¹H, ³¹P and ¹³C NMR spectroscopy, C H analyses and single crystal x-ray diffraction. A preliminary study of the reactivity of both the amido and aryloxo complexes suggests that because of the increased electron affinity of the heteroatoms involved (N or 0), there is high electron density at the heteroatoms in these complexes and therefore the M-N or M-O bond can heterolyze more easily than M-C bonds. This increased tendency of the M-N or M-O bond to heterolyze leads to decomposition reactions when attempts are made to open up a coordination site at the metal center by removing the chloride ligand.
Ph. D.

In this PhD thesis recent developments in Iron and Ruthenium Catalysts for the Reduction of C=O and C=N bonds are reported. In Part A the synthesis and reactivity of new iron complexes promoting the reduction of C=O and C=N bonds is reported. The state of the art in homogenous iron catalyzed hydrogenations is introduced in Chapter 1 followed by the results obtained with each class of iron complexes. Chapter 2 shows the synthesis, characterization and reactivity of BINOL-derived tetra isonitrile iron complexes. Two different families were designed differing in the length of the arm bearing the isonitrile group. Those complexes proved to promote asymmetric transfer hydrogenation (ATH) and asymmetric hydrogenation (AH) of acetophenone under basic conditions. Although the initial results were encouraging, the further attempts to improve the performances were mostly ineffective. Lack of activity, enantioselectivity and reproducibility issues convinced us to not proceed further. Chapter 3 reports a new class of isonitrile-phosphine ligands called PCCP: a chelating system bearing phosphine and isonitrile groups in the same BINOL-derived scaffold. Design, synthesis and characterization of the PCCP ligand are here reported. Once the corresponding iron complex was obtained, ATH of acetophenone was performed but only racemic 1-phenylethanol was yielded. Synthesis of the second generation of PCCP is still undergoing. Chapter 4 is mainly dedicated to the synthesis and the catalytic properties of the (cyclopentadienone)iron pre-catalyst [bis(hexamethylene) cyclopentadienone] iron complex 81. In the first part of the chapter the synthesis of 81 by the reaction of cyclooctyne with Fe(CO)5 and the investigation of its catalytic properties in C=O bond reduction is reported. As a result of the peculiar reactivity of cyclooctyne, 81 was formed in good yield (56%) by intermolecular cyclative carbonylation/complexation with Fe(CO)5. 81 was fully characterized and its crystal structure was determined by using XRD. Catalytic tests revealed that, upon in situ activation with Me3NO, 81 promotes the hydrogenation of ketones, aldehydes, and activated esters as well as the transfer hydrogenation of ketones and shows a higher activity than the classical “Knölker complex” 30. Studies on the hydrogenation kinetics in the presence of 81 and 30 suggest that this difference in activity is probably caused by the better stability of the 81-derived complex than that of the in situ generated Knölker–Casey catalyst. In the second part of Chapter 4 the first catalytic transfer hydrogenation of non-activated imines promoted by a Fe-catalyst 81 in the absence of Lewis acid co-catalysts is reported. Use of the (cyclopentadienone)iron complex 81 allowed to reduce a number of N-aryl and N-alkyl imines in very good yields using iPrOH as hydrogen source. The reaction proceeds with relatively low catalyst loading (0.5-2 mol%) and, remarkably, its scope includes also ketimines, whose reduction with a Fe-complex as the only catalyst has little precedents. Based on this new methodology, we developed a one-pot catalytic transfer hydrogenation protocol for the reductive amination of aldehydes/ketones, which provides access to secondary amines in high yield without the need to isolate imine intermediates. Chapter 5 is focused on the catalytic performances of BINOL-derived (cyclopentadienone)iron complexes recently synthesized in our group. Those iron complexes showed good activity in asymmetric hydrogenation of ketones and although the ee values are clearly inferior to the best literature examples of ketone asymmetric hydrogenation, they still represent the best results obtained so far with chiral (cyclopentadienone)iron complexes. Their reactivity in imine reduction (AH and ATH) was investigated and the results are reported. Both pre- and in situ formed imines were screened and promising results were obtained for acetophenone-derived imines. Part B of this thesis is focused on the use of ruthenium and Trost Ligand as catalyst for asymmetric hydrogenation of ketones. This research was carried out during my Erasmus+ Placement in LIKAT (Leibniz Institute for Catalysis, Rostock, Germany) under the supervision of Prof. Dr. J.G. de Vries and Dr. Sandra Hinze. In Chapter 6, we described the use of Trost ligand as ligand in the AH of ketones. Trost ligand was screened in the presence of several metal salts and found to form active catalysts when combined with ruthenium sources in the presence of hydrogen and a base. Reaction optimization was carried out by screening different Ru sources, solvents and bases. Under the optimized conditions, the complex formed by combination of Trost ligand with RuCl3(H2O)x in the presence of Na2CO3, is able to promote the AH of several ketones at r.t. with good yields and up to 96% ee. The reaction kinetics measured under the optimized conditions revealed the presence of a long induction period, during which the initially formed Ru species is transformed into the catalytically active complex by reaction with hydrogen.

Cette thèse développe l'étude des complexes de nickel(II) porteurs de ligands carbènes N hétérocycliques (NHC) selon deux axes: la synthèse et la caractérisation de complexes nickelacycliques avec un ligand chélatant carbone-carbone (CNHC, Calkyl); et leur activité catalytique dans la construction des liaisons carbone-carbone (Csp2–Csp2/Csp3) des 1-chalcogènes-azoles par fonctionnalisation des liaisons carbone-hydrogène (C–H). Une série de produits d'addition d'acétonitrile métallacycliques CNHC,Calkyl-Ni(II) cationiques a été synthétisée par élimination d'un ligand cyclopentadiényle des nickelacycles demi-sandwich a 18 électrons de valence parents. Il a été déterminé que les complexes cationiques existaient en tant qu'espèce Ni(II) à 14 électrons de valence en forme de T, insaturée de manière coordonnée et électronique, à l'état solide. L'application de ces nouveaux complexes au couplage croisé du benzothiazole avec les iodoarènes s'est avérée une stratégie efficace dans la formation des liaisons Csp2–Csp2, par la combinaison d'un échafaudage métallacyclique stabilisant avec des ligands labiles. La découverte d'une espèce demi sandwich Ni(II)-(NHC)-(benzothiazolyle) inactif dans l'arylation du benzothiazole, mais actif dans le couplage du benzothiazole avec les iodoalcanes, constitue le premier exemple de construction des liaisons Csp2–Csp3 du benzothiazole avec un catalyseur Ni(II)-NHC
This thesis develops the study of nickel(II) complexes bearing N-heterocyclic carbene ligands (NHC) in two axes: the synthesis and characterization of nickelacyclic complexes with a carbon-carbon chelating ligand (CNHC,Calkyl); and their catalytic activity in the construction of carbon-carbon bonds (Csp2–Csp2/Csp3) of 1-chalcogene-azoles by carbon-hydrogen (C–H) bond functionalization. A series of cationic CNHC,Calkyl-Ni(II) metallacyclic acetonitrile adducts was synthetized by the removal of a cyclopentadienyl ligand from parent 18 valence electron half-sandwich nickelacycles. The cationic complexes were determined to exist as rare coordinatively and electronically unsaturated T-shaped 14 valence electron Ni(II) species, in the solid state. Application of these new complexes to the cross-coupling of benzothiazole with iodoarenes proved to be a successful strategy in Csp2–Csp2 bond formation, by the combination of a stabilizing metallacyclic scaffold with labile ligands. The discovery of a half-sandwich Ni(II)-(NHC)-(benzothiazolyl) species, inactive in the arylation of benzothiazole, but active for the cross-coupling of benzothiazole with iodoalkanes shows the first example of benzothiazole Csp2–Csp3 bond construction with a Ni(II)-NHC catalyst

This thesis examines the effects of coordinating highly sterically demanding and strongly electron donating saturated N-heterocyclic carbenes (NHCs) at late transition metal centres. Chapter III details the synthesis of a range of iridium complexes of the type (NHC)2IrHxCly [x = 1, 2; y = 0, 1], bearing the saturated NHCs 5-Mes, 6-Mes and 7-Mes. Unusually facile activation chemistry is observed in the reaction of [Ir(COE)2Cl]2 with 6-Mes and 7-Mes to form the doubly cyclometallated species (6-Mes')2IrH and (7-Mes')2IrH, which were fully characterised. The responses of these complexes to the addition of dihydrogen and HCl were studied, leading to the controlled synthesis of range of precursors to 14-electron iridium cations. In Chapter IV the formation of low valent iridium cations with weakly coordinating anions is targeted. Isolation of the cationic complexes [(NHC)(NHC')IrH][BArf4] and [(NHC)2IrH2][BArf4] (NHC = 6-Mes, 7-Mes) showcases the stabilising power offered by these expanded ring systems. This allowed the study the interaction of these low valent species with a range of amine-borane substrates which are known to be readily dehydrogenated. Thermodynamic data on the C-H bond activation processes occurring at these iridium centres were able to be obtained due to facile, reversible oxidative addition of C-H bonds across the 14-electron iridium. Chapter V focuses on the effects of increasing the steric bulk of these NHCs to limit the coordination of multiple ligands at the metal centre. Use of 2,6-diisopropyl-phenyl (Dipp) groups on the expanded ring NHCs, instead of mesityl groups, leads to an unprecedented mode of reactivity with [Ir(COE)2Cl]2. Activation and cleavage of C-N bonds in the carbene ring is observed, resulting in an open chain ligand chelating to the metal centre. Activation of the backbone in this manner has allowed the synthesis of saturated NHCs bearing a weakly coordinating anion on the ring. Here the first example of an anionic, saturated NHC is reported. In Chapter VI these highly sterically demanding NHCs are exploited to stabilise active species in low valent gold chemistry. The extreme steric bulk of the 6-Dipp ligand disfavours reduction of Au(I) to Au(0), however the resulting cation is observed to interact strongly with the weakly coordinating anion, [BArf4]-. Thus, attempts were made to optimise the anion and conditions to isolate a catalytically relevant intermediate. The strong donating power of these expanded ring NHCs is also exploited to activate gold hydride complexes of the type (NHC)AuH (NHC = 6-Dipp, 7-Dipp). Analogues of [H3]+ containing gold atoms ([{LAu}2H]+ and [LAuH2]+) supported by expanded ring NHCs were also targeted.

The main focus of this thesis has been directed towards preparation and oxidative carbocyclization of en-, dien- and aza-enallenes. In the first part of this thesis, a stereoselective oxidative carbocyclization of dienallenes was realized. By employing cheap and readily available palladium trifluoroacetate we were able to efficiently cyclize a variety of dienallenes into hydroxylated carbocycles in high yield and high selectivity. This oxidative process was compatible with two different reoxidation protocols: one relying on p-benzoquinone (BQ) as the oxidant and the other employing molecular oxygen as the oxidant. In the second part of the thesis the carbocyclization methodology was extended to include carbocyclization of aza-enallenes. This was achieved in two distinct steps. First, a copper-catalyzed coupling of allylic sulfonamides with bromoallenes was developed, giving access to the corresponding aza-enallenes. Subjecting these substrates to catalytic amounts of palladium acetate, along with BQ as the oxidant, rendered N-heterocycles in good yield. The reactivity of these N-heterocycles towards activated dienophiles was later exploited in a tandem (aerobic) oxidative carbocyclization/Diels-Alder reaction. The third topic involves efficient oxidative arylative/borylative carbocyclization of enallenes. These reactions, catalyzed by palladium acetate, relies on transmetallation of a (σ-alkyl)palladium(II) intermediate with diboranes or arylboronic acids. With this novel methodology we were able to obtain an array of arylated or borylated carbocycles, as single diastereomers, in high yield. Finally, we developed a palladium(II)-catalyzed cyclization of allylic carbamates. This mild, operationally simple, and scalable catalytic reaction opens up access to an array of oxazolidinones in high yield and excellent diastereoselectivity.

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 6: Manuscript.

Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2015.
Cataloged from PDF version of thesis. Vita.
Includes bibliographical references.
Chapter 1. Palladium-Catalyzed Cross-Coupling of Aryl Chlorides and Triflates with Sodium Cyanate: A Practical Synthesis of Unsymmetrical Ureas. An efficient method for palladium-catalyzed cross-coupling of aryl chlorides and triflates with sodium cyanate is reported. The protocol allows for the synthesis of unsymmetrical N,N'-di- and N,N,N'-trisubstituted ureas in one pot, and is tolerant of a wide range of functional groups. Insight into the mechanism of aryl isocyanate formation is gleaned through studies of the transmetallation and reductive elimination steps of the reaction, including the first demonstration of reductive elimination from an arylpalladium isocyanate complex to produce an aryl isocyanate. Chapter 2. Palladium-Catalyzed Synthesis of N-Aryl Carbamates. An efficient synthesis of aryl carbamates was achieved by performing palladiumcatalyzed cross-coupling of ArX (X = CI, OTf) with sodium cyanate in the presence of alcohols. The use of aryl triflates as electrophilic components in this transformation allowed for an expanded substrate scope for the direct synthesis of aryl isocyanates. This methodology provides direct access to major carbamate protecting groups, Sthiocarbamates, and diisocyanates, which are precursors to polyurethane materials. Chapter 3. Structural Reevaluation of the Electrophilic Hypervalent Iodine Reagent for Trifluoromethylthiolation. Hypervalent iodine [lambda]3-benziodoxoles are common electrophilic transfer reagents known for their enhanced stability compared to their non-cyclic analogues. Here we present data showing that chlorobenziodoxole reacts with two different thiolate nucleophiles (thiocyanate and trifluoromethylthiolate) resulting in the formation of stable thioperoxy complexes rather than the expected benziodoxole derivatives. We further report a revised structure for the earlier described electrophilic trifluoromethylthiolation reagent (1), previously believed to contain the benziodoxole framework. Our findings, which are based on a combination of analytical techniques, including the recently introduced crystalline sponge method for X-ray analysis, unambiguously demonstrate that 1 is a thioperoxy compound both in solution and the solid state. Chapter 4. Organometallic Palladium Reagents for Cysteine Bioconjugation. Organometallic palladium reagents for the selective S-arylation of biomolecules are described. This new bioconjugation toolkit provides a highly versatile technique for the fast functionalization of cysteine with aromatic scaffolds under a broad range of reaction conditions (e.g., pH, solvent, temperature). The resulting bioconjugates are stable under basic and acidic conditions, as well as in the presence of external thiol nucleophiles. The substitution pattern on the aryl ring can be varied to achieve high levels of stability toward oxidation. Lastly, new types of bio-therapeutics - stapled peptides and linker-free antibody-drug conjugates - could be synthesized using the new method.
by Ekaterina V. Vinogradova.
Ph. D. in Organic Chemistry

The addition of O-H and N-H bonds across carbon-carbon double bonds offers a direct way of synthesising a variety of organic molecules. These reactions have attracted considerable interest in academic research and the chemical/pharmaceutical industry in recent years due to its atom economy. Nevertheless, there remains a considerably challenge to control the regioselectivity and the stereoselectivity of this reaction. This PhD thesis describes the investigation into the discovery and development of a general method for catalytic hydroamination (HA), hydroalkoxylation and hydrooxyacylation of olefins. Air- and moisture-stable transition metal catalysts were the main focus of this study. The introductory Chapter provides an overview of recent advances in N-H addition reactions involving late transition metal catalysts. In Chapter 2, rhodium and ruthenium complexes were examined as catalysts for the addition of N-H bonds to alkenes. The combination of (RuCl2)n/dppb/AgOTf generated a catalyst effective for the addition of methyl carbamate to norbornene in a modest yield. Copper (II) trifluoromethanesulfonate was discovered to be an efficient catalyst for the addition of carboxylic acids, phenols and alcohols to norbornene. A selection of norbornyl esters and ethers were formed in good to excellent yields. In the following Chapter, the combination of copper (II) trifluoromethanesulfonate and diphosphine ligands was successfully applied to the addition of sulfonamides and carbamates to vinylarenes, 1,3-dienes and norbornene in good to excellent yields. In Chapter 4, the intramolecular hydroamination reaction was developed. The synthesis of several acyclic precursors were described, along with attempts to cyclise them. The chapter ends with the attempted synthesis of tricyclic molecules using a palladium-catalysed methodology. The last Chapter contains experimental procedures and characterisation data of all the compounds synthesised during the course of this project.

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

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

Scopo del presente lavoro di tesi è la sintesi di un complesso di manganese contenente un legante bis N-eterociclico e la sua applicazione come catalizzatore nelle reazioni di idrosililazione e idroborazione di doppi e tripli legami. I composti organici sililati e borilati sono importanti prodotti intermedi in diversi settori della chimica fine grazie alla loro stabilità e alla loro capacità di essere ampiamente funzionalizzati. Idroborazione e idrosililazione, grazie allo sviluppo di catalizzatori appositi, permettono di ottenere questi composti riducendo coprodotti, sottoprodotti e condizioni operative estreme. Generalmente i catalizzatori impiegati industrialmente contengono metalli di transizione costosi, rari e non biocompatibili. Per questo motivo negli ultimi anni la ricerca si è concentrata sullo sviluppo di nuovi catalizzatori a base di metalli della prima serie di transizione tra cui il manganese, noto per essere abbondante sulla crosta terrestre, economico e biocompatibile. I composti N-eterociclici (NHC) sono una classe di leganti tra le più utilizzate poiché oltre a una grossa variabilità di caratteristiche steriche ed elettroniche, consentono di stabilizzare la specie metallica. I complessi N-eterociclici di manganese sono stati scarsamente applicati nelle reazioni di idroborazione e idrosililazione. Per questo motivo, il gruppo dove ho svolto il mio tirocinio si è dedicato a questo tipo di ricerca, sintetizzando e testando un complesso bis-NHC di manganese nell’idrosililazione di carbonili e solfossidi. Il mio lavoro si inserisce all’interno di questo ampio progetto, applicando nuovamente lo stesso complesso su una serie di substrati e reazioni differenti. In particolare, l’idrosililazione è stata applicata su alchini, alcheni e su carbonili (in questo caso attivando il complesso con la luce visibile). Inoltre, si è testata l’attività catalitica del complesso nell’idroborazione di alchini.

This thesis describes a series of studies directed towards the use of aerobic aldehyde C-H activation for the construction of C-C and C-N bonds by the process of hydroacylation. Chapter 1 provides an introduction to the research project and an overview of strategies for hydroacylation. Chapter 2 describes the application of aerobic aldehyde C-H activation for the hydroacylation of vinyl sulfonates and sulfones. A discussion on the mechanism of the transformation, the effect of using aldehydes with different oxidation profiles and the application of chiral aldehydes is also included. Chapter 3 describes the functionalisation of γ-keto sulfonates with particular emphasis on an elimination/conjugate addition strategy, which provides an indirect approach to the hydroacylation of electron rich alkenes. Chapters 4 and 5 describe the application of aerobic aldehyde C-H activation towards the hydroacylation of α,β-unsaturated esters and vinyl phosphonates, respectively. An in-depth discussion on the mechanism and aldehyde tolerance of each transformation is also included. Chapter 6 describes acyl radical approaches towards C-N bond formation with particular emphasis on the synthesis of amides and acyl hydrazides.

Les travaux rapportés dans ce mémoire concernent le développement de la réactivité de N-tosylhydrazones dans la création de liaisons carbone-carbone et carbone-azote ainsi que leurs applications à la synthèse des analogues de l’isocombrétastatine A-4 (isoCA-4), aux propriétés antivasculaires.Au cours de ce travail, des molécules de type 1,1-diaryléthylène furent synthétisées par un couplage pallado-catalysé entre des N-tosylhydrazones et des aryles halogénés. Ainsi, des oléfines polysubstituées avec un motif alcoxyle, analogues de l’isoCA-4, ont présenté des activités biologiques intéressantes. De même, les N-tosylhydrazones constituent des intermédiaires pour la synthèse de 1,5-énynes aromatiques. La cyclisation de ces derniers a pu être contrôlée selon la nature du catalyseur utilisé. En effet, en présence de l’or comme catalyseur, une cyclisation 6-endo-dig majoritaire est obtenue alors qu’en présence du palladium, une cyclisation 5-exo-dig exclusive est observée. Cette méthode permettrait de synthétiser des analogues contraints de l’isoCA-4. Le couplage réducteur, catalysé au cuivre, entre des N-tosylhydrazones et des amines et conduisant à des motifs arylalkylamines fut développé. Enfin, un processus cascade entre des 2’-halogéno-biaryl- N-tosylhydrazones et des amines fournit des dérivés du fluorène par la création d’une liaison CN et d’une liaison CC sur le même atome carbénique
This manuscript reports the development of new metal-catalyzed reactions using N-tosylhydrazones as coupling partners for the creation of carbon-carbon and carbon-nitrogen bonds. These reactions are applied in the synthesis of analogues of isocombretastatine A-4 (isoCA-4), a vascular disrupting agent.First, a palladium-catalyzed cross-coupling reaction between N-tosylhydrazones and aryl halides was developed. By this means, polysubstituted olefins with an alkoxy motif were synthesized and presented good biological activities. Then, aromatic 1,5-enynes were synthesized by a multi-step approach using N-tosylhydrazones as intermediates. The regioselectivity of the cyclisation of these enynes was controlled depending on the reaction conditions. Under gold catalysis, a major 6-endo-dig cyclisation pattern leads to naphthalene derivatives while under palladium catalysis; an exclusive 5-exo-dig cyclisation furnishes benzofulvène derivatives. Conformationnally restricted isoCA-4 analogues could be synthesized by applying this method. A copper-catalyzed reductive coupling between N-tosylhydrazones and amines leading to -branched amine derivatives was also developed. Finally, a cascade reaction between 2’-halo-biaryl-N-tosylhydrazones and amines furnished fluoren scaffold by the formation of CC and CN bonds on the same carbenic atom

De par leurs vastes domaines d’applications, l’élaboration de nouvelles molécules énergétiques constitue une partie importante de la recherche en chimie organique. En outre, les hétérocycles azotés se positionnent comme d’excellents candidats du fait de leur densité et leur fort taux en azote qui garantissent à la fois une grande insensibilité et des propriétés énergétiques intéressantes. Ainsi, le développement de méthodes de synthèse innovantes est nécessaire et constitue un véritable défi. Dans ce contexte, nous nous sommes intéressés au long de cette thèse au développement de nouvelles méthodes de synthèse d’hétérocycles polyazotés et fonctionnalisés. Ainsi, l’étude d’une récente stratégie de synthèse d’(aza)indazoles nitrés, via une réaction tandem Staudinger/aza-Wittig, a pu être réalisée pour nous permettre d’accéder à de potentiels candidats énergétiques. Aussi, une méthode originale de synthèse de dérivés tricycliques de triazapentalène a été développée, à partir de substrats insensibles et facilement accessibles. La génération d’un azote électrophile, indispensable pour réaliser cette transformation, a été assurée par diverses amines hétéroaromatiques en présence d’iode hypervalent. Finalement, la valorisation de ces nouvelles méthodes pour accéder à des cibles pyrotechniques originales est présentée dans la dernière partie de cette thèse
Due to their wide range of applications, the elaboration of original energetic materials represents an important part of research in organic chemistry. Besides, the stability and the high explosive performances of azaheterocycles, provided by their compact and nitrogen rich structures, make them promising candidates for energetic applications. Thus, the development of innovative methodologies is essential and remains very challenging. In this context, we aimed at developing new methodologies to access functionalized nitrogen rich heterocycles. For this purpose, we first investigated a recent strategy giving access to polynitrated (aza)indazoles via a Staudinger/aza-Wittig tandem reaction. A second part was dedicated to the development of an original way to synthesize tricyclic triazapentalene derivatives from non-hazardous and readily available precursors. The generation of electrophilic nitrogen, essential to achieve this transformation, was ensured by various heteroaryl amines in presence of hypervalent iodine in mild conditions.The last part of this work focused on the application of these strategies to access new energetic materials

Kyoto University (京都大学)
0048
新制・課程博士
博士(農学)
甲第20451号
農博第2236号
新制||農||1051(附属図書館)
学位論文||H29||N5072(農学部図書室)
京都大学大学院農学研究科応用生命科学専攻
(主査)教授 小川 順, 教授 三上 文三, 教授 栗原 達夫
学位規則第4条第1項該当

Les interactions non covalentes jouent un rôle clé dans des phénomènes de la biologie chimique tel que la stabilisation de la structure tertiaire et quaternaire des protéines ou la reconnaissance entre des biomolécules tel que protéine-protéine et protéine-ligand. Parmi ces interactions, la liaison hydrogène classique de type amide NH···O=C a fait l’objet de nombreuses études approfondies. En revanche, l’étude d’autres types de liaisons hydrogène impliquant le NH de la fonction amide est plus rare. Nos travaux ont été focalisés sur l’impact d’une liaison NH···S sur les préférences conformationnelles d’amino acides soufrés et de leurs oligomères courts. Nous avons préparé un panel de dérivés protégés des amino acides soufrés non-canoniques suivants : Cys(Me) (acyclique), Attc (thiétane), Atlc (thiolane), Atc (thiane). Ces dérivés ont été caractérisés par des calculs théoriques, par spectroscopie double résonance IR/UV en phase gazeuse, par spectroscopie IR et RMN en solution, et à l’état solide. Nous avons mis en évidence pour ces quatre composés l’existence concomitante d’une liaison hydrogène NH···S inter-résidus formant une structure C6ˠ et d’une interaction NH···O=C formant une structure C5. Une succession de ces motifs combinés C5-C6ˠ stabilisants a été retrouvée dans les oligomères d’Attc. Un autre type de liaison hydrogène NH···S, cette fois-ci intra-résidu et formant une structure C5ˠ, a été caractérisé dans des dimères d’Atlc et d’Atc, associée parfois à une interaction NH···O=C formant un coude ˠ. La force de l’interaction NH···X dans le motif structural combiné C5-C6ˠ a été évaluée par comparaison avec des dérivés protégés amino acides cycliques à 4 chaînons : Attc (X = soufre), (Aatc(Me) (X = azoté), Aotc (X = oxygéné). Le motif C5-C6ˠ était présent dans les trois cas et la comparaison des spectres IR en phase gazeuse et en solution, aidée par des calculs théoriques, nous a permis de déduire une force croissante de la liaison hydrogène NH···X en allant de X=O vers X=S puis X=N
Non-covalent interactions play a key role in chemical biology phenomena such as the stabilization of protein tertiary and quaternary structure or protein-protein and protein-substrate recognition. Among these interactions, the classical amide-type NH···O=C hydrogen bond has been thoroughly studied. The study of other types of non-covalent interactions implicating peptide backbone NH groups is much rarer. This work focused on the impact of NH···S hydrogen bonding on the conformational preferences of thioether amino acid residues and their short oligomers. A panel of capped derivatives of the following non-canonical sulfur-containing amino acids was prepared: Cys(Me) (acyclic), Attc (thietane), Atlc (thiolane), Atc (thiane). These derivatives were characterized computationally, by IR/UV double resonance laser spectroscopy in the gas phase, by IR and NMR spectroscopy in solution, and in the solid state. We demonstrated the concomitant existence of inter-residue C6ˠ NH···S hydrogen bonds and C5 NH···O=C interactions in each of these four compounds. This combined stabilizing feature was also prevalent in Attc oligomers. A different intra-residue C5ˠ NH···S hydrogen bond was characterized in short oligomers of Atlc and Atc, in some cases associated with a ˠ-turn NH···O=C interaction. The significance of NH···S bonding in the combined C5-C6ˠ structural feature of Attc was evaluated by comparison with capped derivatives of other four-membered ring amino acids: Ac4c (cyclobutane), Aatc(Me) (azetidine), Aotc (oxetane). The C5–C6ˠ feature was present in the three heterocyclic residues: comparison of their IR spectra in gas phase and in solution, aided by theoretical calculations, allowed us to identify an increasing strength of NH···X hydrogen bonding from X=O to X=S to X=N

This thesis explores the fundamental reactivity of π-complexes of rhodium and nickel, their reactivity to form well-defined 2-metallaoxetanes, as well as subsequent functionalization chemistry of these rare metallacycles. More generally, we also examine C-O and C-S bond cleavage processes. In Chapter 1, we discuss the history of 2-metallaoxetanes, as well as outline some of the fundamental organometallic chemistry of group 10 transition metal complexes. In Chapter 2, the chemistry of a well-defined 2-rhodaoxetane with unsaturated electrophiles is explored. In all cases, insertion into the Rh-O bond is observed. When electron-deficient alkynes are used as substrates, rhodadihydropyrans are formed. Reactivity studies have found these complexes to be robust. In contrast, when aldehydes are used, the product rhodaacetals are much less stable. Curiously, the aldehyde insertions were found to be reversible. Chapter 3 outlines the reactivity of low-valent nickel complexes with three-membered oxacycles. When epoxides were used, isomerization to the corresponding aldehyde was observed as the primary reaction pathway. Experiments with tetrasubstituted epoxides indicate that these reactions occur via 2-nickela(II)oxetane intermediates. Further, catalytic functionalization was achieved using HBpin or B2pin2. When using oxaziridines as the three-membered heterocycle, N-O oxidative addition was found to rapidly generate oxazanickela(II)cyclobutanes. Fragmentation of these metallacycles resulted in the formation of a mixture of imine and aldehyde products. Chapter 4 discusses the synthesis, mechanism of formation and reactivity of a family of well-defined 2-nickela(II)oxetanes. These nickelacycles are formed with retention of configuration, which had not been observed previously. Computational calculations were performed, which support an unexpected bimetallic mechanism of oxidative addition that would allow for the observed stereochemistry. Reactivity studies indicate that the nickelaoxetanes are susceptible to protonolysis, insertion and oxidatively-induced reductive elimination reactions. Chapter 5 describes the chemistry of nickel with esters and thioesters. For thioesters, Cacyl-S bond cleavage followed by decarbonylation was observed to form methyl-thiolate complexes of nickel(II). In contrast, aryl esters were found to undergo Caryl-O oxidative addition, producing aryl-acetate nickel(II) complexes. Both of these classes of compounds were found to be competent in stoichiometric Suzuki-type cross-coupling reactions, but attempts to render the reactions catalytic have so far been unsuccessful.
Science, Faculty of
Chemistry, Department of
Graduate

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

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For a few years the issue of debentures was restricted to publicly traded companies. From January 2009 through CVM Instruction 476, the Securities Commission has extended access to the capital market issuers allowing private companies could also issue Debentures. This access leads us to question what the main factors in the formation of spread in primary issuances of debentures of non-financial companies, listed and unlisted on stock exchanges in Brazil, from 2009 to 2013, and this is the goal of this work. The next question that seeks to answer is whether there is additional spread in the debentures of unlisted companies, and this is the main specific objective of this study. Also seeks to assess whether the spread is influenced by the tax benefit granted to the investor allocates resources debenture financing infrastructure projects. Additionally, the paper studies the influence of the choice of lead manager of the issuing bank in the formation process of the spread and a possible relationship between the spread of the emission and indicators Profitability, Performance and Indebtedness. The sample is composed only of primary emissions of listed and unlisted companies, which occurred between 2009 and 2013, through the SND - National Debenture System, maintained by ANBIMA. We used the OLS - OLS, estimated with the dependent variable spread and fifteen independent variables, resulting in nine statistically significant variables. The results indicate the existence of an additional premium to non- listed companies; influence in shaping the spread according to the choice of lead manager bank of the process; a statistically significant relationship between financial indicators and the formation of the spread
Por alguns anos a emiss??o de deb??ntures estava restrita a empresas de capital aberto. A partir de janeiro de 2009, atrav??s da Instru????o CVM 476, a Comiss??o de Valores Mobili??rios ampliou o acesso de emissores ao mercado de capitais permitindo que empresas de capital fechado tamb??m pudessem emitir deb??ntures. Este acesso nos leva questionar quais os principais fatores determinantes na forma????o do spread em emiss??es prim??rias de deb??ntures de empresas n??o financeiras, listadas e n??o listadas em Bolsa de Valores no Brasil, de 2009 a 2013, e este ?? o objetivo geral deste trabalho. A pergunta seguinte que se procura responder ?? se existe spread adicional nas deb??ntures de empresas n??o listadas, e este ?? o principal objetivo espec??fico deste estudo. Busca-se tamb??m avaliar se o spread ?? influenciado pelo benef??cio fiscal concedido ao investidor que aloca recursos em deb??ntures que financiam projetos de infraestrutura. Adicionalmente, o trabalho estuda a influ??ncia da escolha do banco coordenador l??der do processo de emiss??o na forma????o do spread e uma poss??vel rela????o entre o spread da emiss??o e indicadores de lucratividade, rentabilidade, desempenho e alavancagem (endividamento e composi????o de d??vida). A amostra ?? composta somente por emiss??es prim??rias, de empresas listadas e n??o listadas, ocorridas entre 2009 e 2013, atrav??s do SND Sistema Nacional de Deb??ntures , mantido pela ANBIMA. Utilizou-se o MQO M??nimos Quadrados Ordin??rios , estimado com a vari??vel dependente spread e com quinze vari??veis independentes, resultando em nove vari??veis estatisticamente significantes. Os resultados apontam a exist??ncia de um pr??mio adicional ??s empresas n??o listadas; a influ??ncia na forma????o do spread de acordo com a escolha do banco coordenador l??der do processo; a rela????o estatisticamente significante entre os indicadores cont??beis e a forma????o do spread

Le sujet de cette thèse se situe dans le cadre général des arylations de nucléophiles catalysées par des complexes de métaux de transitions (Cu, Fe) ou réalisées en absence de ces derniers, dans des conditions compétitives et respectueuses de l’environnement. Ces réactions sont d’une importance majeure pour l’industrie chimique. Dans un premier chapitre est tout d’abord décrit un couplage inédit mettant en jeu un sel d’aryldiazonium et un nucléophile azoté (formation de liaison CAr-N). La méthode procède dans des conditions douces via un système catalytique au cuivre peu coûteux et peu toxique. Les produits de couplage obtenus (Ar-NHet) sont d’un intérêt central dans l’industrie pharmaceutique et agrochimique. Dans une deuxième partie nous avons présenté une méthode permettant de réaliser le couplage entre des sels d’aryldiazonium et des dérivés du styrène, à l’aide d’un système t BuOK/DMF. Cette réaction, réalisée pour la première fois en absence de catalyseurs à base de métaux de transition, permet d’accéder, via la formation de liaisons CArsp²-Csp², à des motifs stilbènes variés qui trouvent de nombreuses applications en chimie pharmaceutique. Un deuxième chapitre porte sur l’utilisation de dérivés de l’iode hypervalent permettant la fonctionnalisation de noyaux aromatiques (C-H) ou de dérivés vinyliques (C-H). Une première méthode décrit une réaction de triflimidation directe de composés acétanilides avec une sélectivité exclusive en position para. Deux conditions réactionnelles ont été mises en place pour cette fonctionnalisation. Une première utilise une quantité stœchiométrique de PhI(OAc)2 et une autre utilise une quantité catalytique d’iodotoluène (génération in-situ de l’iode(III)). Cette transformation a conduit à la formation de liaisons CAr-N en présence de bis(trifluorométhane)sulfonimide de lithium (LINTf2) comme nucléophile azoté. Dans une deuxième partie, nous avons montré que l’iodure de bisphosphoranilidène (PNPI), pouvait catalyser la trifluorométhylation vinylique sélective de dérivés du styrène en présence d’un réactif de l’iode hypervalent (l’iode(III)), le réactif de Togni II. Des travaux sont en cours pour tenter de comprendre l’influence positive de l’utilisation de PNPI dans le cas de notre réaction. Un troisième chapitre décrit des résultats préliminaires permettant d’obtenir un rendement honorable (54%) lors du couplage catalysé au fer du 4-iodotoluène avec le phényllithium. Une autre série de test décrit le couplage entre des halogénures d’aryle et des alkyllithium primaires. La méthode semble très efficace, puisque par ailleurs les travaux très récents de la littérature pour des couplages similaires faisant intervenir les mêmes partenaires réactionnels, font appel à des catalyseurs de fer ou de palladium
This thesis is part of a very general search seek to develop methodologies for environmentally sustainable conversion of small molecules into more valuable substances catalyzed by copper and iron complexes or under metal-free conditions. The work focuses on the functionalization of aromatic rings by C-C or C-N bond formation.In a first chapter, a novel coupling involving an aryldiazonium salt and a nitrogenous nucleophile (CAr-N bond formation) is first described. The method proceeds under mild conditions using a cheap and non-toxic copper catalyst system. The obtained coupling products (Ar-NHet) are of central interest in the pharmaceutical and agrochemical industry. Then in a second part, a method allowing the coupling between aryldiazonium salts and styrene derivatives, using a BuOK / DMF system is presented. This reaction, carried out for the first time in the absence of catalysts based on transition metals, makes it possible to access to various stilbene units which find numerous applications in pharmaceutical chemistry.A second chapter concerns the use of hypervalent iodine derivatives allowing the functionalization of aromatic or vinyl substrates. A first method describes a direct triflimidation reaction of acetanilide compounds with an exclusive selectivity in the para position. Two reactions conditions have been established for this functionalization. One uses a stoichiometric amount of PhI(OAc)2 and another uses a catalytic amount of iodotoluene (in-situ generation of iodine (III)). This transformation resulted in the formation of CAr-N bonds in the presence of lithium bis (trifluoromethane) sulfonimide (LINTf2) as the nitrogen nucleophile. In a second part, we have shown that bisphosphoranilidene iodide (PNPI) can catalyze a selective vinylic trifluoromethylation of styrene derivatives in the presence of a hypervalent iodine reagent (iodine (III)), Togni’s reagent II. Work is under way to try to understand the positive influence of PNPI.A third chapter describes preliminary results of an iron-catalyzed heterocoupling of 4-iodotoluene an phenylithium system allowing the obtention of an honorable yield (54%) during the coupling of 4-iodotoluene with phenyllithium. Another series of tests describes the coupling between aryl halides and primary alkyllithiums. The method seems to be very effective, since very recent work in the literature for similar couplings involving the same reaction partners involves catalysts of iron or palladium

Les travaux rapportés dans ce mémoire concernent le développement de nouvelles réactions métallo-catalysées pour la création de liaison carbone-hétéroatomes ainsi que leurs applications à la synthèse d’inhibiteurs de la protéine de choc thermique 90.Au cours de ce travail, l’étude de la réactivité d’hétérocycles de type quinoxalinones et N-aminoazoles vis-à-vis du couplage de Buchwald-Hartwig a été réalisée. Des conditions ont ainsi pu être développées pour créer la liaison carbone-azote entre des 3-chloroquinoxalinones et des partenaires nucléophiles azotés (amides, azoles…) afin de construire une bibliothèque d’analogues du 6BrCaQ en série quinoxalinone. Par ailleurs, la création de la liaison carbone-azote de motifs N-aminoazoles avec des partenaires hétérocycliques halogénés (coumarines, quinoléines…) ou aromatiques halogénés a été étudiée. Celle-ci a permis l’accès à une chimiothèque d’analogues du 6BrCaQ ainsi que le développement du couplage permettant la mono- ou di-substitutions des motifs N-aminoazoles.Dans le dernier chapitre de ce manuscrit, la création de la liaison carbone-soufre en série glycosidique métallo-catalysés (Pd et Ni) entre des thioglycosides et divers aglycones électrophiles (halogénures (hétéro)aromatiques, vinyliques et acétyleniques) a été examiné. Tous les composés obtenus lors de ce travail sont en cours d’évaluation biologique
The development of new metal-catalyzed reactions to form carbon-heteroatom bonds have been studied in order to access to hsp90 inhibitors. For this purpose, reactivity of various 3-chloroquinoxalinone have been explored towards Pd-catalyzed Buchwald-Hartwig reaction with nitrogen nucleophiles (amides, azoles…) which allow access to a serie of 6BrCaQ analogues. In the same objective, the reactivity of N-aminoazole moieties in a Buchwald-Hartwig cross-coupling reaction has been also performed. This methodology led to the synthesis of new 6BrCaQ analogues. Moreover, conditions have been defined to access mono- or di-arylated N-aminoazoles structures starting from aryl chlorides. Finally, reactivity studies on metal-catalyzed carbon-sulfur bond forming reaction between thioglycosides as new nucleophiles partners with various aglycon halides ((hetero)aromatics, alkenyls and alkynyls halides) have been performed. Thanks to a nickel- or a palladium-catalysis, we have been able to introduce these thiosugars on various electrophiles partners and complex molecules. Thioglycosylated 6BrCaQ has been thus obtained.Biological evaluations of new synthesized compounds are currently in progress

L’objectif de ce travail fut la synthèse de ligands fonctionnels de type N,N'-diphosphanyl-NHC (NHC = carbènes N-hétérocycliques) et l’étude de leur chimie de coordination. La synthèse du nouveau ligand tridentate, stable et rigide, N,N'-diphosphanyl-imidazol-2-ylidene a permis des études expérimentales et théoriques et l’accès à des complexes mono-, di-, tri-, penta-, et hexanucléaires des métaux du groupe 11 (Cu, Ag et Au) originaux et aux propriétés structurales uniques. Les complexes mono- et dinucléaires avec un ou deux atomes de phosphore libres ont permis d’accéder à des complexes hétérotrinucléaires à interactions d10-d10 qui sont luminescents. La transmétallation partielle ou totale des complexes homotrinucléaires de Cu ou d’Ag avec des réactifs contenant du Pd(0) ont conduit à des complexes hétérotrinucléaires à interactions d10-d10. En plus de son comportement pontant, ce ligand peut se agir en chélate dans des complexes du palladium et du chrome. Dans le cas du Cr(III), ils montrent une activité catalytique en oligomérisation de l’éthylène supérieure à celle des complexes du Cr(II) et conduisent principalement à des oligomères
The purpose of this work was the synthesis of N,N'-diphosphanyl-functionalized NHC ligands andtheir coordination chemistry. The novel stable and rigid tridentate N,N'-diphosphanyl-imidazol-2-ylidene was synthesized and experimental and computational information on its stability weregained. It served as a unique platform for the synthesis of novel mono-, di-, tri-, penta-, hexanuclear complexes with the coinage metals (Cu, Ag and Au), exhibiting rare structural features. The mono- and dinuclear complexes with one or two dangling P-donors provided rational access to heterotrinuclear complexes. All these coinage metal complexes have short metal-metalseparations, indicating the presence of d10-d10 interactions, and display excellent luminescentproperties. Partial or complete transmetallation of the homotrinuclear Cu or Ag complexes withPd(0) precursors led to hetero-trinuclear complexes with d10-d10 interactions. In addition to itsbridging behavior, this ligand also showed its chelating behavior in Pd or Cr(III) complexes. Thelatter displayed superior performance in ethylene oligomerization than the Cr(II) complexes andgave mostly oligomers

La demanda constant de compostos enantiomèricament purs (fàrmacs, agroquímics, additius...) ha impulsat el desenvolupament de la catàlisi asimétrica emprant compostos organometàl.lics quiral com a catalitzadors. En aquest context, la síntesis de nous lligands quirals és essencial per descobrir bons sistemes catalítics en catàlisi asimètrica. Aquesta tesi s'ha centrat en el desenvolupament de tres noves lligandoteques quirals heterodadores i la seva aplicació a la substitució al·lílic catalizada per paladi. Es tracta de lligandoteques estables a l'aire, de fàcil manipulació i que s'han sintetizats en poques etapes a partir de productes d'elevada disponibilitat i baix preu. Combinant estudis teòrics i espectroscòpia de RMN, hem pogut afinar racionalment els lligands, millorar l'enantioselectivitat i identificar les espècies responsables dels resultats catalítics. A més a més, els productes de substitució al·lílic resultants es van utilitzar amb èxit per a la síntesi de molècules més complexes.
La demanda constante de compuestos enantioméricamente puros (fármacos, agroquímicos, aditivos...) ha impulsado el desarrollo de la catálisis asimétrica empleando compuestos organometálicos quiral como catalizadores. En este contexto, la síntesis de nuevos ligandos quirales es esencial para descubrir buenos sistemas catalíticos en catálisis asimétrica. Esta tesis se ha centrado en el desarrollo de tres nuevas ligandotecas quirales heterodadoras y su aplicación a la sustitución alílica catalizada por paladio. Se trata de ligandotecas estables al aire, de fácil manipulación y que se han sintetizado en pocas etapas a partir de productos de elevada disponibilidad y bajo precio. Combinando estudios teóricos y espectroscopia de RMN, hemos podido afinar racionalmente a los ligandos, mejorar la enantioselectividad e identificar las especies responsables de los resultados catalíticos. Además, los productos de sustitución alílica resultantes se utilizaron exitosamente para la síntesis de moléculas más complejas.
The constant demand for enantiomerically pure compounds (drugs, agrochemicals, additives ...) has driven the development of asymmetric catalysis using chiral organometallic compounds as catalysts. In this context, the synthesis of new chiral ligands is essential to discover good catalytic systems in asymmetric catalysis. This thesis has focused on the development of three new heterodonating chiral ligand libraries and their application to Pd-catalyzed allylic substitutions. These are ligand libraries stable in the air, easy to handle and have been synthesized in a few steps from readily available products and at low price. Combining theoretical studies and NMR spectroscopy, we were able to rationally fine-tune the ligands, improve enantioselectivity, and identify the species responsible for catalytic performance. In addition, the resulting allylic substitution products were successfully used for the synthesis of more complex molecules.