No description available.

The synthesis and characterization of novel complexes of silver supported by sterically demanding, highly electrophilic N-heterocyclic carbene (NHC) ancillary ligands, is described. Stable hydride, fluoride, alkoxide, alkyl, aryl, and alkynyl complexes are characterized by NMR spectroscopy and X-ray diffraction crystallography, and their reactivity is investigated. The interaction of silver centers in dinuclear complexes is probed by 109Ag NMR spectroscopy. Relevance to renewable fuel technology is demonstrated through the mediation of fundamental chemical transformations, including the heterolysis of hydrogen, the transfer of hydride to carbon dioxide, and the formation of carbon-carbon bonds. Kinetic studies shed light on the mechanism of hydrogen activation by hard-soft mismatched complexes of silver, and a formal catalytic cycle for the hydrogenation of carbon dioxide to formate derivatives is reported.

The combination of Lewis acidic f-block metals and a labile nucleophilic carbene can be an excellent means to activate small molecules such as silanes, CO2 and other traditionally inert substrates. Furthermore, bidentate alkoxy-NHC ligands have shown promise in the support of unusual high oxidation state organometallic complexes, including examples of CeIV, PdIV and UVI. In this thesis the synthesis and reactivity of a series of f-block metal NHC complexes is described. Chapter One introduces N-heterocyclic carbenes and their f-block metal complexes, in particular of cerium, praseodymium and uranium. Furthermore, it will give an overview of small molecule activation by NHCs, lanthanides and specifically [Ce(LAr)N"], (L = OC(CH3)2CH2(CNCH2CH2NMes) the magnetic properties and use of lanthanides e.g. as single molecule magnets and oxo-functionalisation of the uranyl moiety. Chapter Two describes the addition-elimination reaction chemistry of CeIII and UIV NHC complexes in which polar reagents add in a heterocyclic fashion across the MNHC bond. It also describes the synthesis of the lithium salt of the alkoxycarbene proligand [LiLAr]4 and its reactivity towards f-element halide and aryloxide salts. A series of reactions to target the formation of metal-metal bonds is described. Chapter Three focuses on the synthesis of novel cerium and praseodymium complexes [Pr(LAr)N"2], [Pr(LAr)2N"], [Pr(OAr2,6-tBu)3] and [Ce(OAr2,6-tBu)3] and their reactivity towards oxidants. A series of alkoxide bridged lanthanide dimers [(Cl)Ce(μ- LAr)2Ce(Cl)2], [N"(LAr)Ce(μ-OAr2,6-tBu)OAr2,6- 2Ce(LAr)N"] and [N"(Cl)Pr(μ LAr)2Pr(Cl)N"] have been made and characterised including by SQUID variable temperature magnetometry. Chapter Four evaluates the synthesis and reactivity of uranyl complexes [UO2(LAr)2], [UO2N"2(py)2] and [UO2(OAr2,6-tBu)2(py)2], specifically their reactivity towards haloboranes in different solvents. Additionally, the oxo-functionalisation of uranyl compounds with haloboranes is discussed. Chapter Five draws conclusions and provides a summary of the work presented. Chapter Six comprises the experimental details and analytical data.

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

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.

Les réactions de couplage métallocatalysées mises en avant par l'attribution du Prix Nobel de Chimie 2010 permettent la création de liaison C-C impossible par les réactions de type SN1 ou SN2. Or, les composés auxquels elles donnent accès sont très utilisés dans le domaine pharmaceutique, agrochimique ou encore dans celui de la chimie supramoléculaire. Si les réactions sont efficaces, les agents de couplages sont souvent peu accessibles et/ou peu éco(nomique/logique)-compatibles. Les triarylbismuthines lèvent en partie ces limitations, car tous les atomes de ces organométalliques participent aux processus et ces composés sont considérés comme non toxiques mais les réactions engageant ce type d'organométalliques souffrent de leur dimérisation. Afin de lever cette limitation, nous avons développé un système catalytique plus " vert" utilisant le PEPPSI comme pré-catalyseur sur une réaction test. Ces nouvelles conditions donnent généralement d'excellents rendements en série biarylique comme hétérobiarylique. La gamme des substituants sur le dérivé halogéné est très étendue mais plus limitée sur la bismuthine. Ce système catalytique a ensuite été utilisé sans modification dans les réactions domino d'élimination/couplage. Une étude cinétique comparative par GC/MS et RMN 13C a permis de montrer qu'une élimination d'ordre 2 avait lieu avant le couplage. De plus il y a un effet coopératif entre les ions fluorures et la bismuthine : celle-ci joue donc un double rôle : agent organométallique doux de couplage et base. L'ambiguïté mécanistique ainsi levée, il a été permis d'envisager une chimiosélectivité en fonction des divers états d'hybridation du carbone portant le brome au moment du couplage. Plusieurs méthodes d'accès à des molécules de structures Ar-Ar-C C-Ar à géométries variables peuvent être obtenues rapidement. Le système catalytique a également permet l'activation de liaison C-Br de bromocoumarines. Ainsi, il est possible de réaliser le couplage sur les positions 3-, 4- et 6-. L'ordre de réactivité a été déterminé ce qui a permis de réaliser des monocouplages parfaitement sélectifs sur les 3,4- ou 3,6- dibromocoumarines, dont les applications biologiques suscitent un grand intérêt. Le nouveau système catalytique a donc éliminé le problème de dimérisation des triarylbismuthines et donne potentiellement accès à des molécules intéressantes pour leurs propriétés physiques ou biologiques / Metallocatalysed crosscoupling reactions have been highlighted by the attribution of the 2010 Nobel Chemistry Price since they allow CC bond formation when classical SN1 or SN2 do not permit it. Furthermore, they give access to many pharmaceutics and agronomic compounds but also molecules used for their supramolecular properties. Nowadays, reactions are really efficient but reactants are not always readily accessible and can't be classified as green reagents. Since all its atoms act over the catalytic process and because they are not considered as toxic so far, triarylbismuthines may be a good alternative to circumvent the limitation described above. However, they suffer a main drawback, their reductive dimerisation. In order to avoid this side-reaction, a new greenest process has been developed on a benchmark reaction based on PEPPSI, an NHC/Pd catalyst. These conditions gave usually excellent yields, either for the biaryle or heterobiaryle crosscoupling reaction. The range of substituents is really wide on the aryle halide moiety but slightly more limited on the triarylbismuthine reagents. Then, this catalytic process has been applied without modification to an elimination/crosscoupling domino reaction. A GC/MS and 13C NMR supported comparative kinetic study showed that a 2nd order elimination take place before the C-C bond formation. Fluoride anion and triarylbismuthine act together. Therefore triarylbismuthine play a dual role: base and aryl transfer reagent. This mechanism study led to chimioselective reactions that allow many paths for the synthesis of Ar-Ar-C C-Ar containing compounds with a good control on geometry of this highly conjugated structure. This catalytic process allows also bromocoumarine C-Br bond activation. Thus, crosscoupling may be selectively performed at the 3-, 4- or 6- position of coumarines. The reactivity order difference of these positions even allow hightly selective mono crosscoupling reaction on 3,4- or 3,6-dibromocoumarines for further biological application. To conclude, our PEPPSI based greenest process avoid the dimerisation of bismuthines and give easy access to many compounds of great interest either for their biological or physical properties

Thesis advisor: Amir H. Hoveyda / Chapter 1. We have developed a single-vessel catalytic protocol for double protoboryl additions to terminal alkynes with B2(pin)2 promoted by Cu complex derived from chiral N-heterocyclic carbene (NHC), to achieve enantiomerically enriched versatile vicinal diborons. Since an alkenyl(pinacolato)boron, which was in situ generated by the first protoboration of a terminal alkyne, can serve as an effective substrate for the second protoboration (alkenylboron can allow delocalization of π electrons of olefin to a partially vacant p orbital on boron), single-vessel catalytic process with 2 equiv. of B2(pin)2 in the presence of sulfonate-bearing chiral NHC–Cu complex, affords enantiomerically enriched 1,2-diborons in up to 93% yield and 97.5:2.5 enantiomeric ratio (e.r.). Site-selective Pd-catalyzed cross-coupling with alkenyl bromide shows the versatility of the resulting diboron compounds, which delivers the coupling product efficiently. Interestingly, only the less hindered, primary C–B bond on vicinal diboron compound participates in the cross coupling. Chapter 2. Cu-catalyzed protocol for selective formation of α-alkenylborons has been demonstrated. With achiral NHC–Cu complex, readily prepared from commercially available imidazolinium salt, various terminal alkynes are converted to internal alkenylborons in up to 93% yield with high to exclusive α selectivity. Propargyl ethers, amides and aryl alkynes are proved to be suitable substrates. Utility of α-alkenylborons is demonstrated by conversion to methyl ketone and synthesis of cyclic alkenylboron compound. In addition, when Cu complex bearing a stronger electron-donating NHC is used, the site selectivity of protoboration reaction becomes reversed, which delivers the alternative isomer, β-alkenylboron efficiently. By altering the steric and electronic nature of NHC, site selectivity is dramatically changed. Mechanistic basis for site selectivity is presented. Chapter 3. Efficient and selective protocol for synthesis of enantiomerically enriched silylborons is described. In the presence of achiral NHC–Cu complex, site- and stereoselective protosilyl additions to terminal alkynes afford a wide range of alkyl- and aryl-substituted (E)-β-alkenylsilanes. Chiral monodentate NHC−Cu complex promotes enantioselective protoboration of alkyl- or alkenyl-bearing alkenylsilanes, delivering vicinal borosilanes with up to 96.5:3.5 e.r. When an alkene bearing both silyl and aryl groups is utilized, on the other hand, geminal silylboron is obtained with high enantio- (93:7–98.5:1.5 e.r.) and site selectivity (up to >98% geminal). In this case, we have reasoned that the electronic attribute of aryl unit is more dominant than the silyl group to control site selectivity. To demonstrate the utility of the Cu-catalyzed transformation, we have illustrated the formal synthesis of bruguierol A, natural product active against Gram-positive and also Gram-negative bacteria. The key intermediate geminal borosilane is provided by sequential NHC–Cu-catalyzed protosilylation and protoboration of terminal alkyne in 77% overall yield with 97.5:2.5 e.r. and 97% site selectivity. Additionally, stereochemical models to account for levels and trends in site- and enantioselectivity are proposed. Chapter 4. New methods for enantioselective protonation of 2-B(pin)-bearing allylcopper, which is in situ generated by site-selective Cu–B addition to 1,1-disubstituted allene, are presented. Transformations are promoted by a chiral NHC–Cu complex, affording an alkenylboron containing α-carbon stereogenic center. Enantiomerically enriched aryl-, heteroaryl- and silyl-bearing alkenylborons are generated in high yield (up to 98%) and selectivities (up to >98% site selectivity and 96.5:3.5 e.r.). To explore the utility of enantiomerically enriched alkenylborons, we have developed Cu-catalyzed enantioselective allylic alkenyl addition to allylic phosphate. A chiral NHC–Cu complex promotes the allylic substitution of enantiomerically enriched alkenylboronic acid with ally phosphate to deliver 1,4-diene in 62% yield with 96:4 d.r. (>98% stereoselectivity). Chapter 5. We have developed a single-vessel, multicomponent process to synthesize N-bearing quaternary carbon stereogenic centers with exceptional diastereo- (>98:2 d.r. for all cases) and high enantioselectivity (88:12 to >99:1 e.r. except one case). Especially, protecting group-free ketoimine (“N–H” ketoimine), which can be prepared by alkylation of a readily available nitrile, has been utilized for the study. The transformation of “N–H” ketoimine is very useful because the obtained amine has no protecting group, which allows us to avoid the deprotection step as well as to be able to choose appropriate protecting group for subsequent chemical reactions. By oxidation of α-tertiary carbamine with NaBO3, β-amino ketones (Mannich reaction product) are obtained in up to 83% yield. A stereochemical model to account for the level of diastereo- and enantioselectivity are presented using DFT calculations. To show the utility of the present method, we have synthesized a medicinally active compound, which was studied for Alzheimer’s disease. The Cu-catalyzed protocol delivers the core structure of the target molecule with exclusive diastereo- and enantioselectivity (>98:2 d.r. and 99.5:0.5 e.r.). / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

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.

Thesis advisor: Amir H. Hoveyda / Chapter 1. In this chapter, the ability of chiral bidentate N-heterocyclic carbenes (NHCs) to activate alkylmetal reagents directly in order to promote C&#8210;C bond forming reactions in the absence of a Cu salt is presented. Highly regio- and enantioselective Cu-free allylic alkylation reactions of di- and trisubstituted allylic substrates with organomagnesium, organozinc, and organoaluminum reagents are demonstrated. Chiral bidentate sulfonate-bearing NHC-Zn and NHC-Al complexes are isolated and fully characterized. Based on crystal structures of these catalytic complexes, mechanistic details regarding Cu-free allylic alkylations with alkylmetal reagents are proposed. Chapter 2. New methods for efficient and highly enantioselective Cu-catalyzed allylic alkylation reactions of a variety of trisubstituted allylic substrates with alkylmagnesium and alkyl-, aryl-, 2-furyl-, and 2-thiophenylaluminum reagents are presented. Transformations are promoted by a chiral NHC complex in the presence of commercially available, inexpensive and air stable CuCl2*H2O. Enantiomerically enriched compounds containing difficult-to-access all-carbon quaternary stereogenic centers are obtained. Chapter 3. New methods for highly site- and enantioselective Cu-catalyzed allylic alkylation reactions of allylic phosphates with vinylaluminum reagents are presented. The requisite vinylaluminums are prepared by reaction of readily accessible terminal alkynes with DIBAL-H and used directly without further purification. Vinyl additions are promoted in the presence of a chiral bidentate sulfonate-based NHC complex and a Cu salt. The desired SN2' products are obtained in >98% E selectivities, >98% SN2' selectivities, >98% group selectivities (<2% i-Bu addition) and high enantioselectivities. The enantioselective total synthesis of the natural product bakuchiol highlights the versatility of the one-pot hydroalumination/Cu-catalyzed enantioselective allylic vinylation process. Chapter 4. Efficient and highly site-selective Cu-catalyzed hydroboration reactions of 1,2-disubstituted aryl olefins with bis(pinacolato)diboron (B2(pin)2) are presented. Transformations are promoted by an NHC-Cu complex in the presence of MeOH, affording only secondary &#946;-boronate isomers. A Cu-catalyzed method for the synthesis of enantiomerically enriched secondary alkylboronates promoted by chiral NHC complexes is disclosed. Chapter 5. A new method for efficient and site-selective tandem Cu-catalyzed copper-boron additions to terminal alkynes with B2(pin)2 in the presence of an NHC-Cu complex is demonstrated. In a one-pot process, Cu-catalyzed hydroboration of alkynes provides vinylboronates in situ, which undergo a second site-selective hydroboration to afford vicinal diboronates. Highly Enantiomerically enriched diboronates obtained through Cu-catalyzed enantioselective dihydroboration in the presence of chiral bidentate sulfonate-based NHC-Cu complex are obtained. The control of site selectivity in the first-stage hydroboration of alkynes is critical for efficient and highly enantioselective reactions in the tandem dihydroboration. Functionalizations of the vicinal diboronates described herein underline the significance of the current method. / Thesis (PhD) — Boston College, 2010. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

N-Heterocyclic carbenes (NHCs) are good ligands to most transition metals forming stable complexes. Many of the NHC-metal complexes are now widely used catalysts. However, the usage of these catalysts encounters the general problems associated with homogeneous catalysis: the purification of the catalysis reaction products is often time-consuming and generates large amounts of waste. Moreover, the toxic or expensive catalysts are difficult to be separated, recycled, and reused. Chapters II and III of this dissertation focus on addressing these problems through the development of an easier and “greener” process to improve the usage of some NHC-metal complexes. Polymer-supported catalysts and polymer-supported sequestrants were prepared and used to facilitate the separation/recycling of catalysts and the purification of products. These polymer-supported ligands, catalysts, and sequestrants showed comparable reactivity to their low molecular weight counterparts and had different solubility properties due to the nature of polymers. Using these materials with the corresponding operations provides simple methods to separate deeply colored, metal-containing by-products from the reaction mixtures. Chapter IV of this dissertation aims at solving a fundamental question about the nature of NHC-silver(I) complexes. The NHC-silver(I) complex is an important synthetic intermediate as it can be used to prepare other NHC-metal complexes through transmetallation. The carbene carbon of an NHC-silver(I) complex in 13C NMR spectra was usually reported as a doublet of doublets or as a singlet in different cases. This phenomenon was explained with a ligand exchange mechanism proposed twelve years ago. However, few reports are available in the literature about the mechanism of the NHC ligand exchange processes at silver. In order to facilitate the study of the solution behaviors of NHC-silver(I) complexes, 13C-labeled NHC-silver(I) complexes were prepared and studied using variable temperature 13C NMR spectroscopy. This study could be useful for future applications of ligand transferring from silver to other metals for the preparation of NHC-metal complexes.