La catálisis es un campo de la ciencia que explora soluciones a los problemas ambientales como la contaminación, la eliminación de los residuos generados en el proceso de síntesis de materiales o la regeneración de los recursos naturales. En la presente Tesis, hemos reportado un estudio de cálculos DFT para la σ activación del enlace NH de amoníaco considerando las especies μ3-alquilidinos de titanio utilizando el complejo modelo [{Ti(η5-C5H5)(μ-O)}3(μ3-CH)]. Posteriormente, con el fin de analizar la hidroformilación asimétrica de estireno catalizada por complejos Rh-Binaphos, se han combinando estudios basados en la aproximación de la determinación del estado de transición y un análisis cualitativo a través de un descriptor molecular recién definido (volumen de distancia ponderada, VW). Usando nuestro conocimiento mecanicista anterior, hemos presentado un estudio QSPR para predecir la actividad y la enantioselectividad de la hidroformilación de estireno catalizada por complejos Rh-difosfinas. También, hemos desarrollado una nueva metodología 3D-QSSR para predecir la enantioselectividad basada en la cuantificación de la representación de diagramas por cuadrantes y aplicándola en el ciclopropanación asimétrica de alquenos catalizadas por complejos de cobre. / Catalysis is a field of science that explores solutions to environmental problems such as pollution, elimination of waste generated in the process of materials synthesis or regeneration of natural resources. In the present Thesis, we have reported a DFT study on the N-H σ-bond activation of ammonia by the µ3-alkylidyne titanium species using the [{Ti(η5-C5H5)(µ-O)}3(µ3-CH)] model complex. Afterwards, we have combined the TS-based approach and qualitative analysis through a newly defined molecular descriptor (distance-weighted volume, VW), in order to analyze the asymmetric hydroformylation of styrene catalyzed by Rh-binaphos complexes. Using our previous mechanistic knowledge, we have presented a QSPR study to predict the activity and the enantioselectivity in the hydroformylation of styrene catalyzed by Rh-diphosphane complexes. We have also developed a new methodology to predict enantioselectivity based on the quantitative quadrant-diagram representation of the catalysts and 3D-QSSR modeling; and we have applied it in the asymmetric cyclopropanation of alkenes catalyzed by copper complexes.

Cocatalyzed reactions using Brønsted acids and chiral N-heterocyclic carbenes to yield highly enantioselective products have been reported recently in many journals. The development of new chiral N-heterocyclic carbenes is a competitive field among synthetic chemist. In a recent study we found that conjugated trienes could be cyclized using Brønsted acids and chiral N-heterocyclic carbenes. The synthesis of novel chiral N-heterocyclic carbene precursors, and the precursors to novel conjugated trienes are reported herein.

This thesis describes an extensive investigation of the O- to C-carboxyl transfer of oxazolyl carbonates using isothioureas as Lewis base catalysts. The structural requirements of simple bicyclic amidines and isothioureas to promote this transformation have been investigated, showing that the catalytic efficiency and product distribution of these reactions are markedly affected by the catalyst structure. The optimal isothiourea catalyst was efficiently applied to the rearrangement of a wide range of oxazolyl, benzofuranyl and indolyl carbonates. The structural motif of tetrahydropyrimidine-based isothioureas has then been evaluated in order to develop an asymmetric variant of the O- to C-carboxyl transfer of oxazolyl carbonates. A number of chiral isothioureas bearing stereodirecting groups in C(2) and/or C(3) have been synthesised and used in this rearrangement, showing that a C(2)-stereodirecting unit is essential for high enantioselectivity, with an additional C(3)-substituent increasing the reactivity. The optimal chiral C(2)-substituted isothioureas identified are general and efficient asymmetric catalysts for O- to C-carboxyl transfer of oxazolyl carbonates, generating a quaternary stereocentre with high enantioselectivity (up to 94% ee). The origin of the enantioselectivity of this process has been probed mechanistically and rationalised computationally. Having gained an insight into the structural motifs of isothioureas required to impart good catalytic activity and asymmetric induction in the O- to C-carboxyl transfer of oxazolyl carbonates, the mechanism of this reaction was probed using kinetic and mechanistic experiments. ¹⁹F NMR spectroscopic analysis allowed the evolution of product, by-product and intermediate throughout the reaction to be monitored while a number of crossover and stability experiments gave additional information about the catalytic cycle. Extension to a related system has been demonstrated with the O- to C-carboxyl transfer of furanyl carbonates, producing a mixture of α- and γ-butenolides depending on the nature of the Lewis base employed. DMAP gives a mixture of both regioisomers with a preference for the α-regioisomer, while NHCs lead predominantly to the γ-regioisomer. Chiral isothioureas have been used to promote this rearrangement, giving the major α-regioisomer with good enantioselectivity (up to 83% ee). To quantify the different reactivities observed with these isothioureas, their nucleophilicities and Lewis basicities using the stopped-flow technique have been determined. Finally, model studies toward the synthesis of the natural product calcaridine A, using the methodology developed herein, have been investigated.

Rhodium-catalyzed hydroacylation is a powerful and atom-economical method for synthesizing ketones from aldehydes and olefins. Despite this, a narrow scope of reactive substrates has limited the utility and broad application of this transformation. Efforts towards the development of new classes of reactive substrates have focused on the use of oxygen- and sulfur-containing olefins, which have enabled various modes of reactivity and thus allowed access to novel types of hydroacylation products. In addition to reactivity, a key to the success of these transformations is the control of regio-, stereo-, and chemoselectivity. In combination with substrate structure, strategies in enantioselective catalysis and metal-organic cooperative catalysis have been applied to achieve requisite reactivity and selectivity when required. A variety of products, such as medium-sized heterocycles, branched sulfur-containing and β-hydroxy ketones, and ketones bearing quaternary carbon centres have been synthesized via hydroacylation using these strategies. A method for preparing polyelectrolyte-stabilized palladium nanoparticles and their use in Suzuki coupling reactions have also been developed.

Rhodium-catalyzed hydroacylation is a powerful and atom-economical method for synthesizing ketones from aldehydes and olefins. Despite this, a narrow scope of reactive substrates has limited the utility and broad application of this transformation. Efforts towards the development of new classes of reactive substrates have focused on the use of oxygen- and sulfur-containing olefins, which have enabled various modes of reactivity and thus allowed access to novel types of hydroacylation products. In addition to reactivity, a key to the success of these transformations is the control of regio-, stereo-, and chemoselectivity. In combination with substrate structure, strategies in enantioselective catalysis and metal-organic cooperative catalysis have been applied to achieve requisite reactivity and selectivity when required. A variety of products, such as medium-sized heterocycles, branched sulfur-containing and β-hydroxy ketones, and ketones bearing quaternary carbon centres have been synthesized via hydroacylation using these strategies. A method for preparing polyelectrolyte-stabilized palladium nanoparticles and their use in Suzuki coupling reactions have also been developed.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第19515号 / 理博第4175号 / 新制||理||1599(附属図書館) / 32551 / 京都大学大学院理学研究科化学専攻 / (主査)教授 丸岡 啓二, 教授 大須賀 篤弘, 教授 依光 英樹 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

There are numerous classes of N-heterocyclic carbenes (NHCs) that have been synthesized since the discovery of stable NHCs in 1988. Their application as ligands in metal complexes has received much attention because of their strong sigma-donor and poor pi-acceptor properties. Within these NHC metal complexes, we are interested in studying zirconium metal complexes with pincer NHC ligands. Recently, achiral CCC-NHC pincer zirconium complexes were synthesized and their catalytic activity in intramolecular hydroamination of aminoalkenes were reported. Herein is reported new reaction conditions which yield pure, chiral CCC-NHC Zr pincer mono(amido) dibromo complex. The enantiopure crystal structure of the same complex is reported. Attempts to synthesize chiral CCC-NHC Zr pincer bis- and tris- amido complexes with the iodo salt of the ligand precursor are summarized. Moreover, syntheses of chiral bis(imidazolinium) ligand precursors with different counter anions are reported with optimized reaction conditions.

Modern organic synthesis typically centers around the use of expensive, complex, homogeneous catalyst systems in organic solvents which often generate copious amounts of hazardous waste. Therefore, the development of water-tolerant catalysts capable of performing reactions in aqueous solutions has become a growing area of scientific inquiry. To this end, we have designed and optimized a water-stable catalyst (Mn[TMPyP4]I5) capable of generating aziridines from olefins in aqueous solutions. Aziridines are valuable synthetic building blocks that have been used to generate various biologically active compounds, though synthetic techniques for aziridine synthesis are not well-established. Our ultimate goal was developing a catalytic system, which could be paired with DNA in order to perform asymmetric transformation in aqueous solutions. Herein we report the optimization of reaction conditions using Mn[TMPyP4]I5 paired with various DNA types, in the hopes of generating chiral aziridines from several olefinic substrates.

Doctor of Philosophy / Department of Chemistry / Christopher J. Levy / Stepped helical salen complexes with vanadium as the central metal were synthesized and characterized. The helicity in these complexes arise from the fused phenyl rings (phenanthryl and benz[a]anthryl) as sidearms, whereas the chirality arises from the chiral cyclohexyl diamine or binaphthyl diamine backbones. These complexes showed good yields and moderate enantioselectivity in asymmetric sulfoxidation reactions with methylphenyl sulfide as the substrate and H2O2 or cumene hydroperoxide as the oxidants. To further improve the closed nature of these complexes with a tetradentate salen ligand, we synthesized and characterized vanadium complexes with tridentate (S)-NOBIN backbone Schiff base ligands with phenanthryl and benz[a]anthryl as the sidearms. After initial catalytic study, we concluded that these catalysts are too open in nature to impose face selection during asymmetric induction. We also synthesized and characterized vanadium and titanium salan complexes. These complexes can adopt β-cis geometry, thereby making the complex “chiral at metal” and they are known for better catalysts in terms of asymmetric induction than their unreduced counterparts. However, these complexes showed better catalytic activity than their unreduced counterparts in sulfoxidation reactions with methylphenyl sulfide as the substrate and H2O2 or cumene hydroperoxide as the oxidants. We also put an effort to synthesize mixed salen complexes with vanadium as the central metal. These complexes have two different sidearms attached to one backbone unit. However, our method did not work well to produce pure mixed salen ligands. The catalysis results for mixed salen vanadium complexes are also comparable to the unreduced vanadyl salen complexes. Lastly, we synthesized and characterized new helical titanium Schiff base complexes with (S)-NOBIN backbone and phenanthryl and benz[a]anthryl sidearms. Single crystal studies showed that these complexes exist in the M helical conformation in the solid state. These complexes showed moderate activity in asymmetric aldol addition reactions between 2-methoxy propene and different aldehydes.

Doctor of Philosophy / Department of Chemistry / Christopher J. Levy / The helix is an important chiral motif in nature, there is increasing development in field of helical transition metal complexes and related supramolecular structures. Hence, the goals of this work are to apply the principles of helicity in order to produce metal complexes with predictable molecular shapes and to study their properties as asymmetric catalysts. Computational studies suggest that the (1R,2R)-cyclobutyldiamine unit can produce highly twisted salen complexes with a large energy barrier between the M and P helical forms. To test this prediction, the tartrate salt of (1R,2R)-cyclobutyldiamine was synthesized and condensed with a series of saliclaldehydes to produce novel salen ligands. The salicylaldehydes chosen have extended phenanthryl or benz[a]anthryl sidearms to encourage formation of helical coordination complexes. These ligands were metallated with zinc, iron and manganese salts to produce salen metal complexes which were characterized by NMR analysis, high-resolution mass spectrometry, and IR spectroscopy. A second ligand type, neutral bis(pyridine-imine) has also been synthesized from (1R,2R)-cyclobutyldiamine and quinolylaldehydes. The synthesis of bis(pyridine-imine) ligands was conducted using greener method, solvent assisted grinding. These ligands, in-situ with nickel metal salts, showed good catalytic activity for asymmetric Diels-Alder reactions. The third ligand type studied was chiral acid-functionalized Schiff-base ligands. These were synthesized by the condensation of 3-formyl-5-methyl salicylic acid and (1R,2R)-cyclobutyldiamine. With this type of ligand, there is possibility of producing both mono and dinuclear metal complexes. In our studies, we were only able to synthesize mononuclear complexs. These were tested as catalysts for asymmetric direct Mannich-type reaction, but were found to be ineffective.