[Rh(CO]2Cl]2 has been shown to catalyze sequential, mechanistically- distinct transformations in one pot. Tandem allylic alkylation/cycloisomerization sequences have been developed to access valuable, complex structures from relatively simple substrates. A methodology for the enantioselective conjugate addition of 2-heteroaryl nucleophiles to a variety of Michael acceptors has been developed. This method was used successfully in an ongoing approach to the synthesis of cortistatin A. 10 linear steps have been completed towards the synthesis of cortistatin A, including a highly regioselective propargylation to install a quaternary carbon and a diastereoselective intramolecular Diels-Alder reaction. / text

Thesis advisor: Marc L. Snapper / A catalyst of notoriety Decomposes with great variety. Transformations after metathesis Facilitate tandem catalysis. This reaction has a proclivity For new regioselectivity With methanolic modification: Tandem enyne hydrovinylation. From a diene protonation event, Unexpected reaction with solvent, During catalyst optimization: One-pot enyne hydroarylation. / Thesis (PhD) — Boston College, 2010. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

The ever-worsening environmental crisis has stimulated development of less wasteful “green” technologies. To this end, tandem catalysis enables multiple catalytic cycles to be performed within a single reaction vessel, thereby eliminating intermediate processing steps and reducing solvent waste. Assisted tandem catalysis employs suitable chemical triggers to transform the initial catalyst into new species, thereby providing a mechanism for “switching on” secondary catalytic activity. This thesis demonstrates the importance of highly productive secondary catalysts through a comparative hydrogenation study involving prominent hydrogenation catalysts of tandem ring-opening metathesis polymerization (ROMP)-hydrogenation, of which hydridocarbonyl species were proved superior. This thesis illuminates optimal routes to hydridocarbonyls under conditions relevant to our ROMP-hydrogenation protocol, using Grubbs benzylidenes as isolable proxies for ROMP-propagating alkylidene species. Analogous studies of ruthenium methylidenes and ethoxylidenes illuminate optimal routes to hydridocarbonyls following ring-closing metathesis (RCM) and metathesis quenching, respectively. The formation of unexpected side products using aggressive chemical triggers is also discussed, and emphasizes the need for cautious design of the post-metathesis trigger phase.

The ever-worsening environmental crisis has stimulated development of less wasteful “green” technologies. To this end, tandem catalysis enables multiple catalytic cycles to be performed within a single reaction vessel, thereby eliminating intermediate processing steps and reducing solvent waste. Assisted tandem catalysis employs suitable chemical triggers to transform the initial catalyst into new species, thereby providing a mechanism for “switching on” secondary catalytic activity. This thesis demonstrates the importance of highly productive secondary catalysts through a comparative hydrogenation study involving prominent hydrogenation catalysts of tandem ring-opening metathesis polymerization (ROMP)-hydrogenation, of which hydridocarbonyl species were proved superior. This thesis illuminates optimal routes to hydridocarbonyls under conditions relevant to our ROMP-hydrogenation protocol, using Grubbs benzylidenes as isolable proxies for ROMP-propagating alkylidene species. Analogous studies of ruthenium methylidenes and ethoxylidenes illuminate optimal routes to hydridocarbonyls following ring-closing metathesis (RCM) and metathesis quenching, respectively. The formation of unexpected side products using aggressive chemical triggers is also discussed, and emphasizes the need for cautious design of the post-metathesis trigger phase.

The ever-worsening environmental crisis has stimulated development of less wasteful “green” technologies. To this end, tandem catalysis enables multiple catalytic cycles to be performed within a single reaction vessel, thereby eliminating intermediate processing steps and reducing solvent waste. Assisted tandem catalysis employs suitable chemical triggers to transform the initial catalyst into new species, thereby providing a mechanism for “switching on” secondary catalytic activity. This thesis demonstrates the importance of highly productive secondary catalysts through a comparative hydrogenation study involving prominent hydrogenation catalysts of tandem ring-opening metathesis polymerization (ROMP)-hydrogenation, of which hydridocarbonyl species were proved superior. This thesis illuminates optimal routes to hydridocarbonyls under conditions relevant to our ROMP-hydrogenation protocol, using Grubbs benzylidenes as isolable proxies for ROMP-propagating alkylidene species. Analogous studies of ruthenium methylidenes and ethoxylidenes illuminate optimal routes to hydridocarbonyls following ring-closing metathesis (RCM) and metathesis quenching, respectively. The formation of unexpected side products using aggressive chemical triggers is also discussed, and emphasizes the need for cautious design of the post-metathesis trigger phase.

The chemical industry is an essential part of modern society and therefore has a responsibility to develop solutions for the problems facing it. A major problem is continuing to match the material demands of a growing global population whilst simultaneously decreasing the consumption of finite natural resources and limiting the emissions of greenhouse gasses. An optimised catalytic system that shortens, or intensifies, the process chain for the production of chemicals can be an effective solution to this challenge. Auto-tandem catalysis is where a single metal-ligand complex facilitates two or more sequential transformations. For example: alkenes are hydroformylated into aldehydes which are then hydrogenated into alcohols. The alcohols have use as plasticisers or surfactants for metal extraction. A previously reported auto-tandem catalysis system was shown to be capable of sequential hydroformylation-hydrogenation of 1-octene to nonanol. It consisted of the neutral rhodium precursor [Rh(acac)(CO)2] and the bidentate ligand xantphos in 10% iPrOH/H2O co-solvent at temperatures of 160°C. Investigations, reported in this thesis, revealed that xantphos type ligands, with their large bite-angle, and high temperatures are required to generate the hydrogenation activity. However, in contrast to the previous system, water is not necessary; with the same results produced in toluene:iPrOH solutions and water:iPrOH solutions. It is proposed that the iPrOH or H2O has a direct influence in the catalytic cycle, either as a hydrogen-shuttle or generates a cationic rhodium species, known to be active in hydrogenation. High temperature NMR studies show the standard resting state of the hydroformylation catalyst is still predominant at high temperatures therefore the proposed catalytic cycle starts from this step. A recurring problem in the industrial process chain is the separation of the catalyst from the final products. Combing a TiO2 ceramic membrane with a POSS (polyhedral oligomeric silsesquioxane) modified tin catalyst and phosphonium iodide co-catalyst, for the coupling of epoxides and CO2 to make cyclic carbonates, was investigated. The catalyst system showed good substrate compatibility for a range of epoxides. In a prototype membrane set-up the system demonstrated a long catalyst life time, however significant leaching was also observed.

[ES] El actual enfoque hacia la desfosilización de la industria química acentúa la necesidad de desarrollar procesos químicos medioambientalmente más sostenibles. El diseño de sistemas catalíticos en tándem para llevar a cabo reacciones mecanísticamente desacopladas en un solo reactor, representa una estrategia prometedora para potencialmente reducir el tamaño de las instalaciones y alcanzar mayores eficiencias energéticas y económicas. El gas de síntesis y sus derivados directos C1 (metanol, DME) representan una atractiva fuente de carbono no derivada del petróleo para la producción de productos químicos. La propagación selectiva de cadena desde compuestos C1 hasta específicamente productos sigue siendo un desafío importante en el campo de la catálisis heterogénea. En esta tesis, se presenta cómo el diseño racional de un sistema catalítico en tándem, multifuncional y heterogéneo, proporciona una ruta novedosa y alternativa para la síntesis directa de productos C3 de interés a partir de compuestos C1. En este trabajo, se ha estudiado la integración en tándem de la reacción de carbonilación de compuestos metoxi (DME) con CO, con la posterior cetonización de los productos carboxílicos C2 intermedios correspondientes en un sistema catalítico multifuncional. La integración de los catalizadores Ag/MOR y Pd/ZrCeOx respectivamente, permite la síntesis directa de acetona a partir de mezclas de DME/gas de síntesis a 548 K y 20 bares. La incorporación de H-FER nanocristalina en un catalizador multifuncional metal/óxido/zeolita Pd/ZrCeOx:FER, como funcionalidad específica de hidrólisis del acetato de metilo, ha permitido la obtención de rendimientos a acetona hasta tres veces mayores en comparación con los obtenidos utilizando solamente el catalizador metal/óxido. La funcionalidad específica de hidrólisis se ha incorporado en base a los resultados de estudios cinéticos realizados para las etapas de reacción por separado, que revelan una limitación general de la velocidad de cetonización a partir del paso de hidrólisis ácida del intermedio acetato de metilo. A una distancia intercatalítica en el rango de micrómetros, se ha mantenido una conversión de DME estable (superior al 94%), junto con una selectividad de acetona del 65-70% (entre los productos orgánicos) durante al menos 10 días de operación continua. Además, la atmósfera de gas de síntesis a alta presión permite la integración de la hidrogenación de grupos carbonilo, abriendo la puerta para la producción de 2-propanol en un solo reactor. En particular, la incorporación del catalizador de hidrogenación Ag-Pt/¿-Al2O3 ha permitido alcanzar una selectividad de 2-propanol del 51% dentro de la fracción de productos C3. Finalmente, el concepto de conversión en tándem mencionado anteriormente se ha extendido a la conversión directa de mezclas de DME/gas de síntesis a propileno. Con este fin, se han desarrollado catalizadores basados en Ag/SiO2 como una funcionalidad de hidrodeshidratación de acetona y se han acoplado al sistema catalítico multifuncional en tándem desarrollado para la producción de acetona. A una temperatura de reacción en el rango de 548-578 K y una presión total de 15 bares, el sistema catalítico en tándem proporciona ratios propileno-a-etileno en el rango 6-9, y selectividades de propileno de hasta el 40%, para una conversión de DME >97%, demostrando que esta ruta de producción es intrínsecamente más selectiva hacia propileno que la mayoría de los procesos de metanol-a-propileno reportados. Además, la temperatura de reacción relativamente suave y el carácter reductor de la atmósfera de gas de síntesis inhiben la deposición de coque, proporcionando un comportamiento estable durante períodos de operación superiores a 214 horas. Aunque se requiere mayor optimización en cuanto al rendimiento a propileno, los resultados abren la puerta a un nuevo proceso para la producción de propileno a partir de materias primas C1, alternativo a los procesos de metanol-a-hidrocarburos. / [CA] L'actual enfocament cap a la desfossilització de la indústria química accentua la necessitat de desenvolupar processos químics mediambientalment més sostenibles. En aquest context, el disseny de sistemes catalítics en tàndem per a dur a terme reaccions mecanísticamente desacoblades en un sol reactor, representa una estratègia prometedora per potencialment reduir la grandària de les instal·lacions i aconseguir majors eficiències energètiques i econòmiques. El gas de síntesi i els seus derivats directes C1 (metanol, DME) representen una atractiva font de carboni no derivada del petroli. La propagació selectiva de cadena des de compostos C1 fins específicament productes C3 continua sent un desafiament important en el camp de la catàlisi heterogènia. En aquesta tesi, es presenta com el disseny racional d'un sistema catalític en tàndem, multifuncional i heterogeni, proporciona una ruta nova i alternativa per a la síntesi directa de productes C3 d'interés a partir de compostos C1. En aquest treball, s'ha estudiat la integració en tàndem de la reacció de carbonilació de compostos metoxi (DME) amb CO, amb la posterior cetonització dels productes carboxílics C2 intermedis corresponents en un sistema catalític multifuncional. La integració dels catalitzadors Ag/MOR i Pd/ZrCeOx respectivament, permet la síntesi directa d'acetona a partir de mescles de DME/gas de síntesi a 548 K i 20 bars. La incorporació d'H-FER nanocristalina en un catalitzador multifuncional metall/òxid/zeolita Pd/ZrCeOx:FER, com a funcionalitat específica d'hidròlisi de l'acetat de metil, intermedi en el procés global, ha permés l'obtenció de rendiments a acetona fins a tres vegades majors en comparació amb els obtinguts utilitzant solament el catalitzador metall/òxid, Pd/ZrCeOx. La funcionalitat específica d'hidròlisi s'ha incorporat sobre la base dels resultats d'estudis cinètics realitzats per a les etapes de reacció per separat, que revelen una limitació general de la velocitat de cetonització a partir del pas d'hidròlisi àcida de l'intermediari acetat de metil. A una distància intercatalítica en el rang de micròmetres, s'ha mantingut una conversió de DME estable (superior al 94%), juntament amb una selectivitat d'acetona del 65-70% (entre tots els productes orgànics) durant almenys 10 dies d'operació contínua. A més, l'atmosfera de gas de síntesi a alta pressió permet la integració de la hidrogenació de grups carbonil, obrint la porta per a la producció no sols d'acetona, sinó també de 2-propanol en un sol reactor. En particular, la incorporació del catalitzador d'hidrogenació Ag-Pt/¿-Al2O3 ha permés aconseguir una selectivitat de 2-propanol del 51% dins de la fracció de productes C3 (és a dir, acetona, 2-propanol, propà i propilé). Finalment, el concepte de conversió en tàndem esmentat anteriorment s'ha estés a la conversió directa de mescles de DME/gas de síntesi a propilé. A aquest efecte, s'han desenvolupat catalitzadors basats en Ag/SiO2 com una funcionalitat de hidro-deshidratació d'acetona i s'han acoblat al sistema catalític multifuncional en tàndem desenvolupat per a la producció d'acetona. A una temperatura de reacció en el rang de 548-578 K i una pressió total de 15 bars, el sistema catalític multifuncional en tàndem proporciona ràtios propilé-a-etilé en el rang 6-9, i selectivitats de propilé de fins al 40%, per a una conversió de DME >97%, demostrant que aquesta ruta de producció és intrínsecament més selectiva cap a propilé que la majoria dels processos de metanol-a-propilé reportats. A més, la temperatura de reacció relativament suau i el caràcter reductor de l'atmosfera de gas de síntesi inhibixen la deposició de coc, proporcionant un comportament estable durant períodes d'operació superiors a 214 hores. Encara que es requereix una major optimització quant al rendiment a propilé, els resultats obrin la porta a un nou procés per a la producció de propilé a partir de matèries primeres C1, alternatiu als processos de metanol-a-hidrocarburs. / [EN] The present focus on advancing towards a defossilized chemical industry underscores the need for developing more environmentally sustainable chemical processes. In this context, the design of tandem-catalytic systems to steer mechanistically decoupled reactions in a cascade fashion, in a single reactor, represents a promising strategy for potentially reduce the installed size of chemical processes and attain higher energy- and cost-efficiencies. Synthesis gas and its direct C1 derivatives (methanol, DME), represent an attractive non-petroleum derived carbon source for the production of commodity chemicals. The selective chain propagation from C1 building blocks to specifically C3 compounds has been demonstrated through biocatalytic routes, however it remains an important challenge for heterogeneous catalysis. In this thesis, we report how the design and engineering of a multifunctional, heterogeneous tandem-catalytic system provides a novel and alternative route for the direct synthesis of C3 compounds from C1 building blocks. The selective obtention of C2+ products with specific chain lengths, surpassing the inherently non-selective C-C chain propagation characteristic of Fischer-Tropsch polymerization reactions, poses a significant challenge. In this work, the tandem integration of the reaction of carbonylation of methoxy compounds (DME) with CO, with subsequent ketonisation of the corresponding C2 carboxylic intermediate products on a multifunctional catalytic system is reported. The integration of an optimized Ag/MOR and Pd/ZrCeOx catalysts, respectively, allows the direct synthesis of acetone from DME/syngas mixtures at 548 K and 20 bar. Enhanced acetone time-yields, i.e. by a factor greater than three, have been obtained by incorporation of nanosized H-FER, as a specific ester hydrolysis functionality in a Pd/ZrCeOx:FER metal/oxide/zeolite multifunctional ketonisation composite catalyst. The specific hydrolysis functionality was implemented based on insights from kinetic studies on the individual reaction steps revealing overall ketonisation rate limitation from the methyl acetate intermediate acid-catalysed hydrolysis step. At the micro-meter range carbonylation/ketonisation intercatalysts spacing, a noticeably stable DME conversion (of >94%), alongside ca. 65-70% acetone selectivity (within all organic products) has been sustained for at least 10 days on-stream. Furthermore, the high-pressure syngas atmosphere allows integrating the hydrogenation of carbonyl groups therefore opening the door for the production of not only acetone but also 2-propanol in a single reactor. Particularly, Ag-Pt/¿-Al2O3 hydrogenation catalyst afforded reaching a 2-propanol selectivity of 51% within the C3 products fraction (i.e. acetone, 2-propanol, propane and propylene). Finally, the above tandem conversion concept has been extended to the direct conversion of DME/syngas mixtures to propylene. To this end, Ag/SiO2 catalysts have been developed as an acetone hydrodehydration functionality and coupled to the multifunctional catalytic-tandem system developed for acetone production from DME/syngas mixtures. At a reaction temperature in the range of 548-578 K and a total pressure of 15 bar, the multifunctional catalytic system affords a remarkably high propylene-to-ethylene molar ratio of 6-9 and overall propylene selectivities up to 40%, at essentially full DME conversion (>97%), proving this production route intrinsically more selective to propylene than most of methanol-to-propylene processes. Moreover, the comparatively mild reaction temperature and the reducing character of the syngas atmosphere inhibit coke deposition, leading to stable performance for times-on-stream in excess of 214 hours. While future improvements in propylene time-yield will be required, the results open the door to a new process for propylene production from C1 feedstocks, alternative to methanol-to-hydrocarbons processes. / I would like to thank the Spanish Ministry of Science, Innovation and Universities (MCIU) for my FPU fellowship (FPU17/04751) and the European Research Council (ERC) under the Horizon 2020 research and innovation program (ERC-CoG- TANDEng; grant agreement 864195), which have made possible the realization of this thesis. BASF SE (Ludwigshafen, Germany) is gratefully acknowledged for their support to fundamental research efforts in catalysis, a portion of which has contributed to the outcomes presented in this PhD thesis. I would also like to thank the Spanish Research Council (CSIC) and, particularly, the Institute of Chemical Technology (ITQ), for providing the infrastructure where I have developed my PhD work. Next, I want to thank the Massachusetts Institute of Technology (MIT) for giving me access to their facilities during my short PhD research stay, and to the ALBA synchrotron, especially to the CLÆSS beamline, for the several beamtimes granted. Finally, I would like to thank the department of Chemical and Nuclear Engineering (DIQN) of the Polytechnic University of Valencia (UPV), for hosting me as a teaching assistant over these years / Andrés Marcos, E. (2024). Tandem Catalysis for Selective C1-to-C3 Chain Propagations towards Platform Chemicals Production [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/204891

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第20404号 / 工博第4341号 / 新制||工||1673(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 澤本 光男, 教授 中條 善樹, 教授 竹中 幹人 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

La tuberculose est une maladie causant encore aujourd'hui plus d'un million de mort chaque année. De nouvelles solutions vaccinales sont nécessaires pour enrayer cette épidémie. Les sulfoglycolipides, trouvés chez Mycobacterium tuberculosis, se sont révélés capables d'activer le système immunitaire et pourraient ainsi représenter une solution thérapeutique intéressante dans la création d'un nouveau vaccin. Dans ce cadre, nous avons souhaités élaborer de nouveaux analogues de sulfoglycolipides. Pour cela, nous avons employé une méthode de protection régiosélective par catalyse tandem au chlorure de fer(III) hexahydrate précédemment développée au laboratoire pour préparer les cœurs glycosidiques des différents mimes. La méthode d'alkylation asymétrique développée par Myers a également été utilisée pour la préparation des acides polydéoxypropionates portés par les différents analogues. / Tuberculosis is still responsible for more than one million deaths each year. New therapeutic solutions are needed to fight this disease. Sulfoglycolipids, found in Mycobacterium tuberculosis's cell wall, seem to be able to activate immune system and could represent an interesting therapeutic solution for the development of a new vaccine. In this context, we wished to elaborate new sulfoglycolipid analogues. For the synthesis of the glycoside moieties of these analogues, we have used a tandem regioselective protection catalyzed by iron(III) chloride, previously developed in our laboratory. Myers's asymmetric alkylation has also been used for the synthesis of polydéoxypropionate chains.

L’accès par voie chimique à des oligosaccharides nécessite souvent le recours à de nombreuses étapes de protection-déprotection. Au cours de ce projet de thèse, une méthodologie pour la protection régiosélective et orthogonale des fonctions alcool de disaccharides dérivant de la biomasse a tout d’abord été développée. Les glycopyranosides protégés ont été préparés par catalyse tandem au FeCl3∙6H2O en réalisant dans le même pot des réactions d’acétalation, d’éthérification réductrice, d’acétylation et/ou d’ouverture réductrice régiosélective d’acétals. Dans un second temps, une stratégie de synthèse flexible, rapide et performante pour accéder à des sulfoglycolipides diacylés et tétraacylés comportant un cœur tréhalose a été mise au point. Ces molécules sont produites par Mycobacterium tuberculosis, l’agent pathogène responsable de la tuberculose, et les sulfoglycolipides diacylés pourraient permettre l’élaboration d’un nouveau vaccin contre cette maladie. Des sulfoglycolipides diacylés et tétraacylés comportant des chaînes monométhylées chirales ont été obtenus. Les précurseurs des acides gras chiraux utilisés au cours de la synthèse ont été analysés par spectroscopie RMN du deutérium en abondance naturelle dans des cristaux liquides chiraux. / The synthesis of oligosaccharides often requires long sequences of protection-deprotection steps. For a rapid access to suitably protected glycopyranosides, we have developed a one-pot regioselective protection strategy based on FeCl3∙6H2O-tandem catalyzed reactions (acetalation, acetylation, reductive etherification, regioselective ring opening of acetal). This procedure was applied to persilylated disaccharides derived from biomass. This methodology allowed the development of a fast, efficient and flexible access to diacylated and tetraacylated sulfoglycolipids based on a trehalose core. These molecules are found in the cell wall of Mycobacterium tuberculosis and the diacylated sulfoglycolipids appear to be promising candidates for the development of a new tuberculosis vaccine. Synthetics diacylated and tetraacylated sulfoglycolipids bearing chiral monomethylated fatty chains were produced. The chiral fatty-acid precursors, used in the procedure, were synthetized and analyzed by NMR spectroscopy of natural abundance deuterium in chiral liquid crystals.