Réaction organique | EPFL Graph Search

Les réactions organiques sont des réactions chimiques impliquant des composés organiques. Les principaux types de réactions organiques sont l'élimination, l'addition, la substitution, le réarrangement et les réactions d'oxydoréduction impliquant des composés organiques. Ces réactions sont utilisées en synthèse organique pour construire de nouvelles molécules organiques. La production de nombreuses substances chimiques, comme les médicaments, les plastiques, les additifs alimentaires, etc., met en jeu des réactions organiques. Les plus anciennes réactions organiques réalisées par l'homme seraient la combustion de combustible et la saponification de corps gras pour obtenir du savon. La chimie organique moderne commence avec la synthèse de Wöhler en 1828. L'histoire des remises de prix Nobel en chimie est jalonnée de découvertes de réactions organiques particulières, comme la réaction de Grignard en 1912, celle de Diels-Alder en 1950, celle de Wittig en 1979 ou la métathèse des alcènes e

Rational Design of Pd-Based Catalysts for Selective Alkyne Hydrogenations

Rocio Micaela Crespo Quesada

Traditionally, the search for active and selective catalysts involved a rather tedious "hit-and-miss" approach in which hundreds, if not thousands catalysts were tested until the optimal substance was identified. With the advancing theoretical understanding of catalysis and the development of computational power, a new era of rational catalyst design is dawning. This approach, grounded on first principles, is based on new advances in synthesis, characterization and modeling with the ultimate aim of predicting the expected behavior of a catalyst based on chemical composition, molecular structure and morphology. The rational design of a catalyst is a complex process which spans across several levels of scale. In this thesis, the pursuit of a rational design for Pd-based catalysts effective in alkyne hydrogenations is presented. A multi-level integrated approach was thus applied ranging from the nano-scale design of the active sites for a specific reaction, taking into account its structure sensitivity, to the micro-scale design of the supported Pd nanoparticles including metal-additive and metal-support interactions as well as mass and heat transfer phenomena. In order to rationally design a catalyst at a nano-scale, i.e. a catalyst's active site, several methodologies have been hitherto applied, such as the study on single crystals or model catalysts. Here we present the use of metal nanoparticles with tuned sizes (5-30 nm) and shapes (cubes, octahedra and cube-octahedra) prepared via colloidal techniques. These nanoparticles can be tested per se and represent a new generation of model catalysts, complementing single crystal studies, which inherently lack the complexity of industrial catalysis. However, metal nanoparticles, especially those prepared in a controlled manner in order to tailor their shape and size, require the use of stabilizing and/or capping agents capable of directing their growth. These substances can mask the true catalytic behavior of the nanoparticles. Thus, it is of great importance to study the interactions of the active phase with the substances that are in close contact with it, in the so-called meso-scaled level of rational catalyst design. Therefore, the effect of the nature of the stabilizing agent on the catalytic response was studied, as well as the promoting effect of some of these substances. Finally, a methodology was developed capable of eliminating organic stabilizing agents from the surface of nanoparticles without compromising their morphological stability. The knowledge gathered in the first two levels can be applied further to reach the microscale rational catalyst design. In this thesis, a final catalyst consisting on well-defined stabilizer-free supported Pd nanoparticles was used in the hydrogenation of acetylene. This deep study of the catalytic behavior of well-defined Pd catalysts throughout several levels of scale and complexity have given us the tools needed to perform a rational catalyst design for alkyne hydrogenations. Depending on the specific reaction, the active phase can be optimized in terms of the desired activity and selectivity and can be tuned even further with the use of specific additives. Finally, the appropriate support also exerts a promoting effect on the nanoparticles and ensures their anchoring in addition to avoiding heat and mass transfer artifacts.

EPFL2011

Novel Applications of Nitrous Oxide and Transition Metals for C-C and C-N Bond Formation

Gregor Kiefer

This thesis describes novel methods for and investigations into C–C and C–N bond formation reactions. Chapter 1 gives a very brief overview of established strategies for the formation of new C–C bonds in organic synthesis. In chapter 2, a multi‐step one‐pot synthesis is described. Arylalkynes and ethylene are converted to 2‐arylbutadienes by ruthenium catalyzed enyne metathesis. Upon addition of polyhalogenated substrates, the butadienes react in a 1,4‐atom transfer radical addition (ATRA) to yield 1,5‐dichloropen‐2‐enes. These form substituted vinylcyclopropanes via reductive 1,5 dechlorination with magnesium or manganese. Chapter 3 describes a study about two complex organometallic structures that form by reaction of rhodium(III) chloride with tert‐butylacetylene. The reaction products demonstrate the ability of rhodium to mediate various reactions of alkynes such as [2+2+1] cycloadditions, oxidative cleavages and others. Cobalt‐catalyzed reactions for C–C bond formation are reported in chapter 4. In the first part, the focus lies on the putative pre‐catalysts [CoX2(dppe)] (X = Cl, Br, I; dppe = diphenylphosphinoethane), which are used together with a reducing agent (e. g. zinc) in a wide range of C–C bond formation reactions. It is shown that they are, in reality, complex salts of the formula [CoX(dppe)2]2[X3Co(dppe)CoX3]. The second part describes the synthesis and characterization of the complexes [CoX(dppe)(PPh3)] and [CoX(dppe)(η4‐isoprene)]. Without addition of a reducing agent, these cobalt(I) complexes catalyze reactions that are usually accomplished with the catalyst system Co(II)/dppe/Zn. These results provide evidence that the active species in these reactions are indeed Co(I) complexes as supposed. In the fifth chapter, two methods for the use of nitrous oxide (N2O, laughing gas) in organic reactions are described. The challenge of using N2O in synthetic chemistry is to overcome its kinetic inertness. In the oxidative homo‐ and cross‐coupling of Grignard reagents, N2O takes the role of an oxidizing agent. The reactions proceed under mild conditions with copper, iron and cobalt salts as catalysts and exhibit high turnover numbers. The utilization of N2O has advantages compared to established methods with other oxidation agents such as oxygen. Furthermore, a procedure for the synthesis of triazenes from lithium dialkylamides, N2O and Grignard reagents is described. This method enables the synthesis of aryl and alkyl triazenes, but also alkenyl and alkynyl triazenes that are difficult to access via established procedures. Some alkynyl triazenes are selectively cytotoxic against certain cancer cell lines.

EPFL2015

Copper-catalyzed transformations of carboradicals generated by electrochemical and photochemical methods: oxidative amination and polyfluoroarylation

Xiangli Yi

Organic radicals are highly active species that can undergo various transformations. Electrochemistry and photochemistry are efficient methods for the generation of these species of high energy, through single electron transfer processes under mild conditions. These methods have been frequently used to form various carboradical intermediates, for example, via the addition of N-centered radicals to alkenes (Section 1.4). Copper is a versatile transition metal that can transform carboradicals for the formation of various chemical bonds (Section 1.6). Combining electrochemistry or photochemistry for the generation of carboradicals with the copper-catalyzed carboradical functionalization will potentially lead to a large chemical space of useful organic reactions. So far, this intersection of electrochemistry or photochemistry with copper chemistry is still highly underdeveloped. In this thesis, we have developed three useful reactions, testifying the practicability of this concept.In Chapter 2, we describe an intramolecular oxidative amination reaction by integrating electrochemical oxidation with Cu catalysis. Electrochemical oxidation facilely generates N-radical from N-H for the intramolecular cyclization to double bonds, and then the resultant carboradicals are transformed into a new double bond via copper-catalyzed oxidative elimination (Section 1.6.1). A wide range of 5-membered N-containing heterocycles bearing a pendant, functionalizable alkene moiety can be synthesized under mild conditions. Mechanistic studies revealed that direct oxidation on the electrode couldn't efficiently convert primary and secondary alkyl radical intermediates into alkenes, and that the assistance of copper was indispensable.In Chapter 3, an intermolecular oxidative amination reaction of unactivated alkenes by integrating photoredox with Cu catalysis is described. This method relied on photochemical reduction of a hydroxyamine derivative to generate amidyl radical which then adds to unactivated alkenes. The obained carboradicals are trapped by the copper catalyst to form allylic amines. The reaction exhibited a broad scope and excellent tolerance for functional groups including highly polar groups. In Chapter 4, we report a decarboxylative coupling reaction of aliphatic acids with polyfluoroaryl nucleophiles by integrating photoredox with copper catalysis. A set of polyfluoroaryl zinc reagents were prepared and applied to the coupling. The aliphatic esters of N-hydroxyphthalimide (NHPI esters) were transformed into alkyl radicals by photoreduction. Then, the trapping of the radical by the copper catalyst and subsequent reductive elimination render the alkyl polyfluoroarenes as products. This method allows the installation of polyfluoroaryls with variable F-content (2F -5F) and F-substitution patterns on primary or secondary alkyl groups, with good compatibility of functional groups. In summary, this thesis demonstrates the combination of electrochemistry and photochemistry with copper catalysis to construct useful synthetic methods. Considering the diversity of radicals that could be generated by electrochemical and photochemical methods, and the versatility of copper catalyzed functionalization of carboradicals, we believe that this combination has far more potential than these three reactions.

EPFL2021