Transition Metal Catalyzed Reductive Cyclization Reactions of Nitroarenes and Nitroalkenes

Nitroarenes are the entry point for the production of most nitrogen-containing aromatic compounds. Thus, any transformation that leads directly from them to the final product allows saving one or more synthetic steps. This review deals with homogeneously catalyzed reactions leading to the formation of N-heterocyclic compounds from nitroarenes or nitroalkenes in one pot. Reactions that lead to the intermediate formation of amines are not considered. Carbon monoxide is the most often employed reductant because it allows selective reactions, is cheap, and only produces CO2 as stoichiometric byproduct. However, the difficulty in handling pressurized CO has stimulated in recent years the development of CO-surrogates, that is molecules able to liberate CO during the reaction. The use of phosphines and diols has also been developed in conjunction with molybdenum catalysts. The review focusses in more detail on the literature in the period 2006\u20132018, but reference to earlier work is made when necessary to put recent results in a more general context

HOMOGENEOUS CATALYTIC REDUCTIVE CARBONYLATION OF ORGANIC NITRO COMPOUNDS: BIDENTATE NITROGEN LIGANDS AS A KEY POINT

The reductive carbonylation of nitro compounds is a process with a high potential synthetic and industrial interest, since many products can be obtained from nitro compounds and CO, including isocyanates, carbamates, ureas and heterocyclic compounds. The most active systems in this kind of reactions are based on the use of a transition metal catalyst and a nitrogen ligand. In this PhD thesis studies on reduction by carbon monoxide of palladium complexes relevant to the reaction of carbonylation of nitroarenes are reported. Moreover catalytic studies were conducted on the use of differently substituted nitrogen ligands in the palladium catalyzed synthesis of methyl N-phenylcarbamate. In particular the effect of non symmetric ligands on the activity of the catalytic system and the use of long alkyl chain substituted phenanthrolines for catalyst recycling are discussed. A system based on a palladium/phenanthroline complex was also investigated for the reductive cyclization of beta-nitrostyrenes to indoles: the optimization of the reaction and its scope are reported

Reduction of nitro compounds using 3d-non-noble metal catalysts

The reduction of nitro compounds to the corresponding amines is one of the most utilized catalytic processes in the fine and bulk chemical industry. The latest development of catalysts with cheap metals like Fe, Co, Ni, and Cu has led to their tremendous achievements over the last years prompting their greater application as "standard" catalysts. In this review, we will comprehensively discuss the use of homogeneous and heterogeneous catalysts based on non-noble 3d-metals for the reduction of nitro compounds using various reductants. The different systems will be revised considering both the catalytic performances and synthetic aspects highlighting also their advantages and disadvantages

Towards a sustainable synthesis of aromatic isocyanates : by the palladium diphosphane catalyzed reduction of nitrobenzene; a first step

Aromatic isocyanates are annually produced on the megaton scale from nitro arenes. A major problem with current synthetic strategies is that they utilize the extremely toxic phosgene to carbonylate a reduced nitroaromatic. More sustainable strategies have been known for decades, in particular the palladium catalyzed reductive carbonylation of nitro arenes with CO in methanol. The lack of a clear mechanistic understanding of this reaction, however, has thus far hampered the development of sufficiently active and selective catalysts; the generation of such understanding is therefore the prime aim of this thesis. Thus, the palladium catalyzed reductive carbonylation of nitrobenzene with CO in methanol was studied in detail, wherein palladium was supported by a variety of diphosphane ligands of different steric and electronic nature. The general mechanistic pictured that emerged form these studies, is that nitrobenzene reduction chemistry is catalytically coupled with methanol oxidation chemistry by a complex network of catalytic reactions that are centred around a palladium-imido complex (__P2Pd2+=NPh__). This catalytic coupling provided a unique opportunity to gather mechanistic insights for both reactions, but also makes the system needlessly complicated when only nitrobenzene carbonylation products are desired. Several other nucleophiles were considered and 2,2,2-trifluoroethanol was identified as promising alternative to methanol.UBL - phd migration 201

REDUCTIVE TRANSFORMATIONS OF THE NITRO GROUP: FROM HOMOGENEOUS TO HETEROGENEOUS CATALYSIS

This thesis focuses its attention into two different aspects of catalysis. In the first part, transition-metal complexes were used as homogeneous catalysts for the preparation nitrogen-containing heterocycles (especially indoles) using liquid sources of carbon monoxide. In the second part, in collaboration with Prof. Matthias Beller (Leibniz Institute for Catalysis-LIKAT, Rostock), doped-carbon heterogeneous non-noble metal catalysts were employed as catalytic materials in the hydrogenation of nitroaromatics. In both cases, nitro compounds were used as valuable starting materials corroborating their central role in organic chemistry. Equally, mechanistic aspects (especially kinetics) were taken into account showing how they can play a pivotal role in understanding not only the specific reaction mechanism but also how a catalytic system can be further improved

Catalytic transformation of oxygen containing compounds into valuables : effect of ceria redox properties

The focus of this thesis is the investigation of sustainable routes for the production of commercially valuable oxygen containing compounds through the application of ceria-based catalysts. The catalytic transformation of levulinic acid (to γ-valerolactone), CO2, methanol and nitrobenzene (to methyl-N-phenyl carbamate), 1butanol (to 1-butene) and 1,3-butanediol (to 3-buten-2-ol) have been examined. Taking the conversion of levulinic acid as a model system, it was established that the surface oxygen vacancies, formed during temperature programmed reduction of reducible oxides, activate levulinic acid for reaction. Process sustainability has been examined in terms of full hydrogen utilisation with 100% yield of the target γ-valerolactone under stoichiometric conditions over supported Au catalysts. The production of the carbamate directly from CO2 was initially optimised towards dimethyl carbonate formation as a reaction intermediate, where the highest reported rate has been achieved. It was shown that total surface area of CeO2 is not a determining parameter for catalytic performance, while a decrease in Ce3+ content upon calcination improves CO2 activation. Dehydration of 1-butanol/1,3-butanediol revealed the requirement for the strong Lewis acid sites on the surface of the catalyst to form an alkene. The results presented in this thesis demonstrate direct participation of the ceria in the catalytic dehydration and carboxylation reactions

Amide Formation via Ni-Catalyzed Reductive Coupling Reactions with Isocyanates

Recentment, les reaccions d’acoblament creuat entre electròfils s’han posicionat com a potents alternatives a les reaccions clàssiques d’acoblament creuat entre electròfils orgànics i nucleòfils organometàl•lics. Aquests acoblaments reductius presenten nombrosos avantatges degut a que utilitzen compostos de partida simples i fàcilment assequibles que eviten la necessitat de sintetitzar espècies organometàl•liques sensibles a la humitat i a l’oxigen. Com a conseqüència, els protocols experimentals són pràctics i les condicions de reacció són suaus. A causa de la ubiqüitat de les amides en molècules biològicament actives tals com pèptids, agroquímics, productes farmacèutics o materials sintètics, s’ha impulsat un continu desenvolupament de nous mètodes eficients basats en la síntesis d’amides. La present tesis doctoral, està centrada en el desenvolupament de nous acoblaments reductius creuats catalitzats per níquel per la síntesis d’amides utilitzant isocianats com a sintons. Concretament, es presenta i es desenvolupa un nou protocol destinat a la síntesis d’amides alifàtiques a partir de bromurs d’alquil primaris, secundaris i terciaris combinats amb isocianats d’aril o d’alquil. Tanmateix, s’inclou el desenvolupament d’una metodologia per la hidroamidació altament diastereoselectiva d’alquins ans isocianats per la formació d’acilamides. Aquest protocol utilitza bromurs d’alquil com a font per la formació d’hidrurs in situ. Finalment, es presenta una discussió dels resultats preliminars sobre l’amidació regiodivergent, retentiva i remota de bromurs d’alquil secundaris inactius. Les transformacions desenvolupades aquí constitueixen nous mètodes per la síntesi d’amides mitjançant la formació d’enllaços C-C catalitzada per metalls i es caracteritza per les condicions suaus, l’ampli abast de la reacció, la seva excel•lent regioselectivitat i alta tolerància amb diversos grups funcionals.Recientemente, las reacciones de acoplamiento cruzado entre electrófilos se han posicionado como potentes alternativas a las reacciones clásicas de acoplamiento cruzado entre electrófilos orgánicos y nucleófilos organometálicos. Dichos acoplamientos reductivos ofrecen numerosas ventajas, ya que utilizan compuestos de partida simples y fácilmente asequibles que evitan la necesidad de sintetizar especies organometálicas sensibles a la humedad y al oxígeno. Debido a ello, los protocolos experimentales son prácticos y las condiciones de reacción suaves. La ubiquidad de las amidas en moléculas biológicamente activas tales como péptidos, agroquímicos y productos farmacéuticos, así como en materiales sintéticos, impulsa continuamente el desarrollo de nuevos métodos para la síntesis eficiente de amidas. La presente Tesis Doctoral, se centra en el desarrollo de nuevos acoplamientos reductivos cruzados catalizados por níquel para la síntesis de amidas, utilizando isocianatos como el sintón correspondiente a la amida. Específicamente, se presenta un nuevo protocolo para la síntesis de amidas alifáticas a partir de bromuros de alquilo primarios, secundarios y terciarios en combinación con isocianatos de arilo y alquilo. Asimismo, se incluye el desarrollo de una metodología para la hidroamidación altamente diastereoselectiva de alquinos con isocianatos para la formación de acrilamidas. Dicho protocolo utiliza bromuros de alquilo como fuentes suaves para la formación de hidruros in situ. Finalmente, se discuten resultados preliminares sobre la amidación regiodivergente, retentiva y remota, de bromuros de alquilo secundarios inactivados. Las transformaciones desarrolladas aquí constituyen nuevos métodos para la síntesis de amidas mediante la formación de enlaces C-C catalizada por metales y se caracterizan por sus condiciones suaves, su amplio alcance de reacción, su excelente regioselectividad y alta tolerancia a diversos grupos funcionales.Recently, cross-electrophile couplings have become powerful alternatives to classical cross-coupling reactions that are based on nucleophile/electrophile regimes. Starting from readily available building blocks, reductive couplings are practical and mild protocols that circumvent the use of moisture and air-sensitive organometallic species. The ubiquity of amides in biologically relevant molecules such as peptides, agrochemicals and pharmaceuticals, as well as in polymers, continually prompts the design of novel methods for amide synthesis. This Doctoral Thesis focuses on the development of novel nickel-catalyzed reductive protocols for the synthesis of amides using isocyanates as the amide synthon. Specifically, we have discovered a novel protocol for the synthesis of aliphatic amides from primary, secondary and tertiary alkyl bromides in combination with aryl and alkyl isocyanates. A methodology for the highly diastereoselective hydroamidation of alkynes with isocyanates to afford acrylamides has been developed, with alkyl bromides used as in situ and mild hydride sources. Finally, efforts towards the regiodivergent retentive and chain-walking amidation of unactivated acyclic secondary alkyl bromides are discussed. The transformations developed herein are characterized by their mild conditions, wide substrate scope and excellent chemo- and regioselectivity, and constitute novel methods for the formation of amides via metal-catalyzed C—C bond formation

I. Mechanistic significance of the Si-O-Pd linkage in the cross-coupling of organosilanolates; II. Applications of the water-gas shift reaction in organic synthesis

The first half of the present dissertation describes the mechanistic investigation of the palladium-catalyzed cross-coupling reaction of alkenyl- and arylsilanolates. The combination of reaction kinetics (both stoichiometric and catalytic), solution and solid state characterization of arylpalladium(II) organosilanolate complexes, and computational analysis, enabled the formulation of a detailed mechanistic picture for the cross-coupling of these classes of nucleophiles. The intermediacy of covalent adducts containing Si-O-Pd linkages in the cross-coupling reactions of organosilanolates has been unambiguously established. From such intermediates, two mechanistically distinct transmetalation pathways have been demonstrated: (1) transmetalation via a neutral 8-Si-4 intermediate (thermal transmetalation); (2) transmetalation via an anionic 10-Si-5 intermediate (activated transmetalation). In general, potassium salts of alkenylsilanolates react via neutral intermediates (8-Si-4), whereas the enhanced nucleophilicity of cesium alkenylsilanolates allows for the reaction to access the 10-Si-5 intermediate and proceed via the anionically-activated pathway. However, if the direct transmetalation is slower, as in the case of arylsilanolates (which require interruption of aromaticity), then anionic activation via the 10-Si-5 intermediate is predominant, regardless of the cation employed. These conclusions mandate a revision of the paradigm that organosilicon compounds must be anionically activated to engage in transmetalation processes (Hiyama-Hatanaka paradigm). Through the agency of the critical Si-O-Pd linkage, direct transmetalation of silicon to palladium can be achieved under mild conditions without anionic activation. The thorough mechanistic understanding of the transmetalation step for organosilanolates was leveraged in the study of the cross-coupling of γ-disubstituted allenylsilanolates. For the cross-coupling reaction of this class of nucleophiles, it was concluded that the transmetalation pathway (activated vs. thermal) dictates which isomer is accessed (α vs. γ). The second half of this dissertation details the efforts made toward the application of the Water-Gas Shift Reaction (WGSR) in the catalysis of fundamental C-C bond forming reactions. To this end, three strategies were envisioned and investigated. In a first approach, the CO/H2O couple was exploited as the terminal reducing agent for a metal catalyst that is directly involved in the formation of a new C-C bond. This strategy was studied in the context of carbonyl addition and reductive homocoupling reactions. The multiple conditions that must be strictly met for this approach to be successful (ranging from electrochemical requirements to properly balanced bond enthalpies of the complexes along the catalytic pathway) made the development of new, WGSR-based catalytic methods quite challenging. In a second approach, the CO/H2O couple provides reducing equivalents for an organocatalyst that is implicated in the C-C bond formation. This second strategy poses fewer challenges because it consists of two independent catalytic processes: a metal-catalyzed one for the WGSR, and an organo-catalyzed one for the formation of the C-C bond. This strategy was used in the development of a catalytic, Wittig-type olefination reaction. It was demonstrated that the use of tributylstibine enabled catalytic turnover under WGSR conditions. A third, simpler approach to engage the WGSR in C-C bond formation relies on the well-established capacity of CO/H2O to act as a H2 surrogate. In this approach, an independent C-C bond forming event leads to a functional group that can be reduced (hydrogenated) by CO/H2O. The metal catalyst for the WGSR is not involved in the formation of the C-C bond, but only in the generation of a metal-hydride species that will hydrogenate the substrate. The outcome is an overall reductive, tandem transformation that combines two steps in one, therefore enhancing step- and redox economy. This strategy has been successfully illustrated in the tandem Knoevenagel condensation/reduction reaction, in which an alkene formed by Knoevenagel condensation is readily reduced under WGSR conditions. The compatibility with several classes of electrophiles and nucleophiles under mild conditions has been demonstrated, resulting in a method that is comparable and, for certain aspects, even superior to established alkylation or reductive alkylation protocols

Towards sustainability in hydrogenation and hydroformylation reactions

The work focuses on the usage of the base-metal cobalt in order to endeavor a replacement of noble-metal based industrial and academic systems. An earlier published system for the cobalt-based hydrogenation of carbon dioxide was improved by ligand-modification to a 2.5-fold turnover number. Also, the activity of this system in the hydrogenation of organic carbonates to the corresponding alcohols was demonstrated for the first time. Besides, supported cobalt nanoparticles have been proven to be active for selective olefin hydrogenations and investigated for heterogeneous hydroformylations.Diese Arbeit befasst sich mit der Anwendung des günstigen, unedlen Metalls Kobalt in industriellen und akademischen Systemen. Die Produktivität eines bekannten, Kobalt-basierten Systems für die homogene Hydrierung von CO2 wurde durch Modifizierung des Liganden mehr als verdoppelt. Des Weiteren wurde die homogene Hydrierung cyclischer und acyclischer Carbonate zu den entsprechenden Alkoholen erstmals mit Kobalt ermöglicht. Ferner wurden Kobalt-Nanopartikel auf anorganischen Trägern oder Kohle in der selektiven Olefin-Hydrierung angewandt und für die heterogene Hydroformylierung getestet