Incorporation of silicon in the ligand backbone would yield electron-rich metal complexes upon coordination to transition metal complexes. The coordination chemistry of semirigid benzyl phosphines bearing a single or multiple phosphorus atoms and varying number of Si−H moieties has gained interest in recent years. This dissertation focuses on synthesizing silyl and germyl transition metal complexes of groups 9 and 10. Chapter II presents the synthesis of a family of four coordinated 14-electron rhodium complexes. The newly synthesized complexes were characterized in solution by multinuclear NMR spectroscopy and in the solid-state by single-crystal X-ray diffraction. These d6 complexes possess sawhorse geometry around the rhodium metal center. The catalytic activity of the synthesized Rh complexes and the analogous Ir complex towards hydrosilylation/ dehydrogenative silylation of alkenes is presented in this study. Importantly, it was observed that the selectivity of the catalytic reaction can modify the choice of the metal center, rendering hydrosilylation products upon the use of Rh or dehydrogenative silylated product upon the use of Ir. In chapter III, the results of our investigations on the catalytic activity in dehydrogenative silylation of alkenes by Rh2(OAc)4/ PPh3 system are presented. Sacrificial hydrogen acceptor, norbornene, and PPh3 play a key role in specificity favoring the dehydrogenative silylated product. The substrate scope and the possible mechanistic pathways are reviewed. Chapters IV and V present the synthesis of EP3-type (E = Si, Ge) tetradentate ligands. We describe the synthesis via E−H bond activation and characterization of their nickel and cobalt complexes by spectroscopic means. Additionally, the solid-state structures of the complexes were confirmed by X-ray crystallography. The catalytic activity of the synthesized nickel hydrides was investigated in the hydroboration of aldehydes by pinacolborane (HBpin). The catalytic activity of the synthesized cobalt(I) complex was studied in the presence of (EtO)3SiH with aldehydes and ketones bearing various functional groups under mild conditions. In Chapter VI, the syntheses of octahedral rhodium and iridium [(Ph2P-o-CH2-C6H4)3E]MClH (M = Rh, Ir: E = Si, Ge) complexes bearing EP3-type tetradentate ligands via EH bond activation are presented. We also describe the synthesis and characterization of platinum complexes supported by EP3-type tetradentate ligands.

In molecular transition metal catalyst architectures, ligand design plays a crucial role in enhancing the efficiency of catalytic reactions. Selected ligands can play a bifunctional role in ligand-assisted catalysis, providing first coordination sphere basic sites and facilitating formation of multinuclear species through monomer bridging, as well as through their electronic and steric effects. This research addresses the underutilization of SNS complexes in various catalytic cycles. Our aim is to expand their activity in different cycles, unlocking untapped reactivity. Specifically, we focus on SNS ligands with soft thiolate and hard amido donors, comparing their catalytic performance in diverse coupling reactions. This comparative study provides insights into the suitability of these ligands with different transition metals, contributing to the understanding of ligand-assisted catalysis. Chapter 1 introduces these concepts and outlines the relevant catalytic reactions studied herein. To gain a deeper understanding of the chemistry involved, a comparative analysis of the reactivity differences between transition metal complexes with similar coordination structures is conducted. This investigation is crucial as it provides valuable insights into the design of suitable ligands for transition metal catalysts. Specifically, Chapters 2 and 3 of this thesis delve into a comparison of the reactivity of coordination complexes with identical metal centers and similar ligands, or even the same molecular formula, in catalysis. In the second chapter, we introduce a new cobalt (II) complex bearing an (SNS) amido ligand for the bifunctional hydroboration of carbonyls. Following an unsuccessful attempt to mono-protonate the amido donor in the bis(amido) complex Co(SᴹᵉNSᴹᵉ)₂ (2.1) treatment with 1 equivalent of 1,3-bis(1-adamantyl)imidazolium chloride (IAd•HCl) resulted in the liberation of one protonated ligand, affording CoᴵᴵCl(SᴹᵉNSᴹᵉ)(a-IAd) (2.2) with an "abnormally" coordinated IAd ligand, i.e., specifically bound through C4 instead of C2 of the imidazole ring. Compound 2.2 exhibited excellent catalytic activity in the hydroboration of aldehydes, displaying high substrate tolerance under mild reaction conditions and short reaction times. Stoichiometric reactions of 2.2 with pinacolborane (HBpin) revealed a bifunctional catalyst activation step, generating free SNS-amine, ClBpin and the active cobalt dihydride catalyst. Generation of an analogous catalyst with a normally coordinated IAd ligand showed poor reactivity in the hydroboration of aldehydes and was unable to effect ketone hydroboration. In Chapter 3, two tetranuclear copper(I) complexes bearing thiolate [Cu(SNSᴹᵉ)]₄ (3.1) and amido [Cu(SNSᴹᵉ)]₄ (3.2) SNS ligands are synthesized and their catalytic activity in a base-free azide-alkyne cycloaddition is compared. Complex 3.1 (1 mol%) demonstrated excellent reactivity for performing this 'click' reaction in water, exhibiting a broad substrate scope and enabling the production of various triazole compounds, including bioactive compound 3.16, which holds potential as an anti-cancer drug. DFT calculations suggested a proton shuttle role for the thiolate donor in conversion of the Cu-coordinated terminal alkyne to the key Cu-alkynyl intermediate. On the other hand, complex 3.2 exhibited reactivity similar to copper chloride. This observation was attributed to the basic nature of the amido ligand, which undergoes protonation by the coordinated alkyne C-H bond, with subsequent dissociation of the SNS-amine from the copper. Without a ligand to stabilize the copper in the less stable +1 oxidation state, a disproportionation reaction occurs, leading to catalyst deactivation. Chapter 4 introduces two palladium(II) thiolate complexes: PdI(κ³-SNSᴹᵉ) (4.1) exhibits catalytic activity in promoting the Heck cross-coupling reaction, while Pd(κ²-SNSᴹᵉ)₂ (4.2) affords no coupling product. In concert with triethylamine base, catalyst 4.1 efficiently produces olefin products with excellent yields, even at low catalyst loadings, and exhibits broad substrate tolerance over a 5 h reaction period. In contrast, the limited catalytic activity of 4.2 can be rationalized by proposing the formation of a Pd(N₂S₂) complex through ligand imine coupling at elevated temperatures, a reaction reported previously for Ni and Co analogs. The tetra-coordinated ligand formed through this isomerization occupies critical coordination sites around the metal, thereby preventing oxidative addition of the organohalide substrate, a key step in the Heck reaction mechanism. This work sheds light on the divergent catalytic behaviors of these two intriguing complexes. Finally, in Chapter 5 we assess what has been learned and identify relevant implications for further work.

Polymer functional groups have critical impacts upon physical, chemical and mechanical properties, and thus affect the specific applications of the polymer. Functionalization of cellulose esters and ethers has been under extensive investigation for applications including drug delivery, cosmetics, food ingredients, and automobile coating. In oral delivery of poorly water-soluble drugs, amorphous solid dispersion (ASD) formulations have been used, prepared by forming miscible blends of polymers and drugs to inhibit crystallization and enhance bioavailability of the drug. The Edgar and Taylor groups have revealed that some cellulose omega-carboxyalkanoates were highly effective as ASD polymers, with the pendant carboxylic acid groups providing both specific polymer-drug interactions and pH-triggered release through swelling of the ionized polymer matrix. While a variety of functional groups such as hydroxyl and amide groups are also of interest, cellulose functionalization has relied heavily on classical methods such as esterification and etherification for appending functional groups. These methods, although they have been very useful, are limited in two respects. First, they typically employ harsh reaction conditions. Secondly, each synthetic pathway is only applicable for one or a narrow group of functionalities due to restrictions imposed by the required reaction conditions. To this end, there is a great impetus to identify novel reactions in cellulose modification that are mild, efficient and ideally modular. In the initial effort to design and synthesize cellulose esters for oral drug delivery, we developed several new methods in cellulose functionalization, which can overcome drawbacks of conventional synthetic pathways, provide novel cellulose derivatives that are otherwise inaccessible, and present a platform for structure-property relationship study. Cellulose omega-hydroxyalkanoates were previously difficult to access as the hydroxyl groups, if not protected, react with carboxylic acid/carbonyl during a typical esterification reaction or ring opening of lactones, producing cellulose-g-polyester and homopolyester. We demonstrated the viability of chemoselective olefin hydroboration-oxidation in the synthesis of cellulose omega]-hydroxyesters in the presence of ester groups. Cellulose esters with terminally olefinic side chains were transformed to the target products by two-step, one-pot hydroboration-oxidation reactions, using 9-borabicyclo[3.3.1]nonane (9-BBN) as hydroboration agent, followed by oxidizing the organoborane intermediate to a primary alcohol using mildly alkaline H2O2. The use of 9-BBN as hydroboration agent and sodium acetate as base catalyst in oxidation successfully avoided cleavage of ester linkages by borane reduction and base catalyzed hydrolysis. With the impetus of modular and efficient synthesis, we introduced olefin cross-metathesis (CM) in polysaccharide functionalization. Using Grubbs type catalyst, cellulose esters with terminally olefinic side chains were reacted with various CM partners including acrylic acid, acrylates and acrylamides to afford families of functionalized cellulose esters. Molar excesses of CM partners were used in order to suppress potential crosslinking caused by self-metathesis between terminally olefinic side chains. Amide CM partners can chelate with the ruthenium catalyst and cause low conversions in conventional solvents such as THF. While the inherent reactivity toward CM and tendency of acrylamides to chelate Ru is influenced by the acrylamide N-substituents, employing acetic acid as a solvent significantly improved the conversion of certain acrylamides. We observed that the CM products are prone to crosslinking during storage, and found that the crosslinking is likely caused by free radical abstraction of gamma-hydrogen of the alpha, beta-unsaturation and subsequent recombination. We further demonstrated successful hydrogenation of these alpha, beta-unsaturated acids, esters, and amides, thereby eliminating the potential for radical-induced crosslinking during storage. The alpha, beta-unsaturation on CM products can cause crosslinking due to gamma-H abstraction and recombination if not reduced immediately after reaction. Instead of eliminating the double bond by hydrogenation, we described a method to make use of these reactive conjugated olefins by post-CM thiol-Michael addition. Under amine catalysis, different CM products and thiols were combined and reacted. Using proper thiols and catalyst, complete conversion can be achieved under mild reaction conditions. The combination of the two modular reactions creates versatile access to multi-functionalized cellulose derivatives. Compared with conventional reactions, these reactions enable click or click-like conjugation of functional groups onto cellulose backbone. The modular profile of the reactions enables clean and informative structure-property relationship studies for ASD. These approaches also provide opportunities for the synthesis of chemically and architecturally diverse cellulosic polymers that are otherwise difficult to access, opening doors for many other applications such as antimicrobial, antifouling, in vivo drug delivery, and bioconjugation. We believe that the cellulose functionalization approaches we pioneered can be expanded to the modification of other polysaccharides and polymers, and that these reactions will become useful tools in the toolbox of polymer/polysaccharide chemists. / Ph. D.

Ce travail de recherche est consacré au développement de catalyseurs à base de métaux de transition abondants de la première rangée du tableau périodique, tels que Mn, Fe, et Ni, pour les réactions d'hydro-élémentation. Tout d'abord, l'hydrosilylation de cétones et d'aldéhydes a été accomplie en utilisant un système catalytique simple Ni(OAc)₂ 4H2O/PCy₃ avec le PMHS, silane peu coûteux et stable en tant que source d'hydrure. L'amination réductrice d'aldéhydes avec des amines a également été réalisée avec le même système catalytique et le TMDS, comme silane. Deuxièmement, l’efficacité des complexes de manganèse demi-sandwich CpMn(CO)₂(IMes) a été prouvée pour la réduction des aldéhydes et des cétones en présence de Ph₂SiH₂ (1,5 équiv.) sous irradiation UV. La transformation difficile d'acides carboxyliques en aldéhydes a été effectuée à l'aide de Mn₂(CO)₁₀ et de Et3SiH. Troisièmement, la méthylation des amines secondaires avec le carbonate de diméthyle en tant que source C1 a été démontrée dans des conditions catalytique douces avec [CpFe(CO)₂(IMes)]I. Ensuite, l'hydroboration d'alcènes et d'alcynes fonctionnalisés a été réalisée en présence d’un complexe de fer (0), Fe(CO)₄(IMes) sous irradiation UV. Enfin, la réaction d'hydroboration a été étendue avec succès à la réduction de CO₂ en methoxyboranes avec Fe(CO)₃[P(OPh)₃]₂ en tant que catalyseur et les diverses sources de borane, tels que HBpin, HBcat ou 9-BBN. / This research work deals with the use of the catalysts based on the earth-abundant transition metals of the first row of the periodic table, such as Mn, Fe, and Ni, for hydroelementation reactions. First of all, the hydrosilylation of aldehydes and ketones was accomplished using a simple Ni(OAc)₂ 4H₂O/PCy₃ catalytic system with the inexpensive and stable silane PMHS as the hydride source. The reductive amination of aldehydes with amines was also achieved with the same catalytic system and TMDS, as the silane. Second, the efficiency of manganese half-sandwich complex CpMn(CO)₂(IMes) was exemplified for the reduction of aldehydes and ketones in the presence of Ph ₂ SiH ₂ (1.5 equiv.) under UV irradiation at room temperature. Still with manganese, the challenging transformation of carboxylic acids to aldehydes was performed using commercial Mn₂ (CO)₁₀ and Et₃SiH. Third, the methylation of the secondary amines with dimethyl carbonate as an alternative and safe C1 source was demonstrated under mild conditions with [CpFe(CO)₂(IMes)]I as the catalyst. Then, the hydroboration of functionalized alkenes and alkynes was catalyzed by an iron(0) carbonyl complex Fe(CO)₄(IMes) under UV irradiation. Finally, the hydroboration reaction was successfully extended to the reduction of CO₂ to methoxyboranes with Fe(CO)₃[P(OPh)₃]₂ as the catalyst and the borane sources, such as HBpin, HBcat or 9-BBN.

Les amphidinolides C et F sont des macrocycles isolés de dinoflagellés Amphidinium sp. vivant en symbiose avec des plathelminthes Amphiscolops sp.. Ces amphidinolides ont montrés des activités cytotoxiques importantes sur des lignées de cellules KB et L1210. Au vu du potentiel thérapeutique intéressant et de l’architecture complexe de ces substances naturelles, un programme de synthèse totale a été initié. Dans ce manuscrit, différentes approches pour la construction de ces produits naturels sont détaillées, les principaux défis étant la création efficace de motifs 2,5-Trans THF, l’incorporation de motifs diénique par des méthodes catalytiques et le contrôle des centres asymétriques grâce à des époxydes chiraux. / Amphidinolides C and F are macrocyles isolated from dinoflagellates Amphidinium sp., which are living in symbiosis with marine flatworms Amphiscolops sp.. Those amphidinolides had shown an important cytotoxic activity against KB and L1210 cell lines. Due to promising therapeutical potential and complex framework of these natural products, a total synthesis program had been initiated. In this manuscript, different approaches for the construction of these natural targets are detailed. The main challenges were the efficient formation of 2,5-Trans THF, incorporation of dienic moieties by catalytic processes and the installation of chiral centers through chiral epoxyde chemistry.

In the context of ongoing efforts toward C-aryl glycoside synthesis, a recently developed approach to form C-aryl glycals from 2-deoxysugar lactones was expanded to form novel substrates. This approach has been applied to the synthesis of various furyl glycals, allowing access to C-aryl glycals via a benzyne furan (4+2) cycloaddition methodology. The hydroboration-oxidation of said C-aryl glycals has allowed access to C(2)-oxygenated C-aryl glycosides via the benzyne cycloaddition approach. An approach to the total synthesis of 5-hydoxyaloin A is detailed, in which regioselective benzyne furan (4+2) cycloadditions were achieved via the use of a silicon tether. Two approaches to the anthrone core have been applied; one in which an unsymmetrically-substituted aryl ring is first constructed by means of a silicon tether, and one in which the unsymmetrically-substituted ring is formed last, also utilizing a silicon tether. The latter approach has allowed access to the anthrone core of 5-hydroxyaloin A, and only a final desulfurization remains in order to access the natural product. / text

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