Academic literature on the topic 'Decarboxylation reaction'

This thesis describes research efforts dedicated to the development of palladium(II)-catalyzed oxidative Heck and Heck/Suzuki domino reactions, and the applications of a new microwave heating technology, purpose-built for continuous flow in organic synthesis. Paper I describes the development of a ligand-modulated approach for attaching aryl groups to a chelating vinyl ether. By switching the ligand being used, selectivity for the arylation could be shifted to obtain three different outcomes: internal α- or terminal β-arylation, as well as a serendipitously discovered domino α,β-diarylation process. The latter was proposed to be an effect of para-benzoquinone, effectively acting as a stabilizing π-acidic ligand with the ability to suppress β-hydride elimination. Paper II explores the performance of a new microwave heating technology in combination with continuous flow. The novel nonresonant microwave applicator allowed rapid heating of common laboratory solvents and reaction mixtures above their boiling points with stable and reproducible temperature profiles. The technology was successfully applied to small-scale method development and subsequent scale-out of palladium-catalyzed reactions, heterocycle synthesis and classical organic transformations such as the Fischer indole synthesis. Paper III focuses on developing regioselective oxidative decarboxylative Heck reactions with electron-rich olefins. Successful internal α-arylations were achieved using various olefins and ortho-substituted aromatic acids. The mechanism was also studied by ESI-MS analysis. Key cationic organopalladium intermediates were identified, as well as an unexpected palladium(II)-complex which was isolated and characterized. Its experimentally deduced structure was in accordance with the lowest energy minimum found by DFT calculations. Preliminary findings suggested that the complex acts as a catalyst trap. Paper IV studies the mechanism of the reaction in Paper III by means of DFT calculations. Reductive elimination was identified as the rate-determining step when using a linear enamide as the olefin, due to its propensity to form low energy chelates. Its chelating properties also played a key role in the stability of the isolated palladium(II)-complex. The complex, which can act as a catalyst trap, was characterized by X-ray crystallography.

Aromatic rings are privileged structures found in a diverse range of natural and synthetic compounds, thus synthetic methods for their functionalisations are important in organic synthesis. Despite significant advancements made, especially in the field of transition metal catalysis, work still continues for the development of milder, more efficient, and more atom economical reactions. We describe here our efforts towards the development of decarboxylative/direct C(aryl)–N and C(aryl)–C bond forming reactions using aromatic carboxylic acids and unfunctionalised arenes as cheap and widely available aromatic sources. The investigations into copper-catalysed and copper/palladium-catalysed intermolecular and copper/silver/palladium-catalysed intramolecular decarboxylative amination of aromatic carboxylic acids are reported. A new approach to decarboxylation of benzoic acids is also described. The reaction uses silver (I) catalyst and peroxydisulfate salt to generate aryl radicals via oxidative decarboxylation. The applications of this approach in intra- and intermolecular decarboxylative C–H arylation, and protodecarboxylation are described. Also described is the development of silver-catalysed trifluoromethylation of simple arenes and heteroarenes. The reaction proceeds via radical trifluoromethylation using trimethyl(trifluoromethyl)silane as the trifluoromethyl radical source. This method has been applied to the trifluoromethylation of complex agrochemical molecules, proving its synthetic utility in late-stage functionalisation. Furthermore, we describe the exploitation of trifluoroacetate derivatives as cheap trifluoromethylating reagents in copper-mediated decarboxylative C–H trifluoromethylation of 2-phenylpyridine.

Basé sur les concepts de développement durable et de chimie verte, l’une des alternatives envisagées par les chimistes, pour une chimie plus propre, est de substituer les solvants organiques, pouvant être dangereux et toxiques, par des solvants plus verts. L’eau est un bon candidat pour cette substitution car c’est le solvant le moins cher dans nos contrées, et le plus sûr : il est non-toxique, ininflammable et non explosif. Afin de palier la faible solubilité de la majeure partie des composés organiques dans l’eau, les tensioactifs peuven têtre utilisés afin d’améliorer les rendements réactionnels. Les milieux ainsi obtenus sont difficilement recyclables car ils nécessitent une forte dilution afin de casser les agrégats et de récupérer les produits. C’est pourquoi, l’utilisation de tensioactifs photo-régulables est une bonne alternative car il est possible d’organiser/désorganiser les agrégats par irradiation lumineuse et ainsi récupérer les composés organiques en fin de réaction tout en recyclant le milieu réactionnel. Pour cela, nous avons synthétisé trois tensioactifs possédant une fonction azobenzène(anionique, cationique, non ionique), afin de les tester en catalyse micellaire. Certains de ces tensioactifs, après en avoir déterminé leurs propriétés physico-chimiques (cmc et spectre UV-Visible) ont été testés dans une réaction pallado-catalysée : la substitution allylique de Tsuji-Trost. Nous avons réussi à démontrer l’intérêt d’utiliser un tensioactif photo-régulable par rapport aux tensioactifs commerciaux en terme de rendement et de recyclabilité. D’autre part, la décarboxylation de Barton, décrite pour la première fois en 1983, permet la formation d’alcanes à partir d’acides carboxyliques en utilisant un dérivé d’étain comme donneur d’hydrogène. Depuis lors, cette réaction a toujours été utilisée comme étape clé en synthèse totale de composés naturels et en solvants organiques. De plus, cette réaction est historiquement réalisée par activation conventionnelle, thermique ou par irradiation ultra-violette. C’est pourquoi, nous avons décidé d’étudier cette décarboxylation radicalaire dans l’eau, en présence de tensioactifs et en utilisant des modes d’activation non conventionnels : les micro-ondes et les ultrasons. De plus, en lieu et place d’étain, nous avons préféré l’utilisation de N-phénylmaléimide, déjà connu et étudié comme piège à radicaux, afin d’obtenir des maléimides substitués par des chaînes carbonées. Les rendements obtenus en milieux micellaires se sont avérés être aussi bons, voire meilleurs qu’en solvants organiques<br>Based on concepts of sustainable development and green chemistry, one of the alternatives envisioned by chemists is to substitute organic solvents, which can be dangerous and toxic, for greener solvents. Water is the best candidate for this substitution because it is thesafest and cheapest solvent in our countries : this solvent is non-toxic, non-flammable and inexplosive. In order to overcome the low solubility of most of organic compounds in water, surfactants can be used to improve the reaction yields. Media thus obtained are difficult to recycle because they require high dilution in order to break aggregates and recover products. Therefore, using photo-switchable surfactants is a good alternative because they can organize/disorganize by light irradiation. Organic compounds could be recovered after reactions and the recyclability of the medium can be improved. For this purpose, we synthesized three surfactants having an azobenzene moiety (anionic,cationic, nonionic), to test them in micellar catalysis. Some of these surfactants, after determining their physicochemical properties (CMCs and UV-visible spectra) were studied in a pallado-catalyzed reaction, the allylic substitution of Tsuji-Trost. We have successfully demonstrated the value of using a photo-switchable surfactant compared to commercialones in terms of yields and recyclability. In other hand, Barton decarboxylation, described for the first time in 1983, permits the formation of alkanes from carboxylic acids, using tin derivatives as hydrogen donors. Since then, this reaction has always been used as a key step in total synthesis of natural compounds in organic solvents. In addition, historically, this reaction was carried out by conventional activation (heat or ultraviolet light). Therefore, we decided to study this radical decarboxylation in water, in the presence of surfactants and using unconventional activation modes : microwave and ultrasound. Moreover, instead of tin, we preferred the use of N-phenylmaleimide, already known and studied as a radical trap, to obtain maleimides substituted by carbon chains. Yields obtained in micellar media were found tobe at least as good as in organic solvents

Ascaris suum NAD-malic enzyme catalyzes the decarboxylation of oxalacetate and reduction of pyruvate. Thus, the present classification (E.C. 1.1.1.39) for this enzyme should be changed to E.C. 1.1.1.38. In the absence of nucleotide, both the chicken liver NADP-malic enzyme and Ascaris suum NAD-malic enzymes catalyze the decarboxylation of oxalacetate. A study of the pH dependence of kinetic parameters for oxalacetate decarboxylation and pyruvate reduction was carried out for the NAD(P)-malic enzyme with Mg^2+ and Mn^2+ in the presence and absence of nucleotide. In all cases, an enzyme residue is required in its protonated form for reaction while for oxalacetate decarboxylation the β-carboxyl of oxalacetate is required unprotonated. Of a number of inhibitory binding analogs of malate tested, oxalate is the tightest binding inhibitor for Ascaris suum enzyme.

Computational methods are very useful tools in the study of enzymatic reactions, as they can provide a detailed understanding of reaction mechanisms and the sources of various selectivities. In this thesis, density functional theory has been employed to examine four different enzymes of potential importance for biocatalytic applications. The enzymes considered are limonene epoxide hydrolase, soluble epoxide hydrolase, arylmalonate decarboxylase and phenolic acid decarboxylase. Besides the reaction mechanisms, the enantioselectivities in three of these enzymes have also been investigated in detail. In all studies, quite large quantum chemical cluster models of the active sites have been used. In particular, the models have to account for the chiral environment of the active site in order to reproduce and rationalize the experimentally observed selectivities. For both epoxide hydrolases, the calculated enantioselectivities are in good agreement with experiments. In addition, explanations for the change in stereochemical outcome for the mutants of limonene epoxide hydrolase, and for the observed enantioconvergency in the soluble epoxide hydrolase are presented. The reaction mechanisms of the two decarboxylases are found to involve the formation of an enediolate- or a quinone methide intermediate, supporting thus the main features of the proposed mechanisms in both cases. For arylmalonate decarboxylase, an explanation for the observed enantioselectivity is also presented. In addition to the obtained chemical insights, the results presented in this thesis demonstrate that the quantum chemical cluster approach is indeed a valuable tool in the field of asymmetric biocatalysis.<br><p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.</p><p> </p>

Nanosecond time-resolved resonance Raman spectroscopy (ns-TR3), nanosecond transient absorption (ns-TA) and femtosecond transient absorption (fs-TA) were utilized to investigate the photochemistry of ketoprofen (KP), ketoprofen-purine dyads, fenofebric acid (FA) in different solutions. For KP, the rate constant and reaction mechanism of KP are strongly dependent on the concentration of water. In neat acetonitrile and acetonitrile-rich solutions (water:acetonitrile?1:1, v:v), KP exhibits mostly benzophenone-like photochemistry to give rise to triplet state which in turn transforms to ketyl radical intermediate by hydrogen abstraction reaction. However, in aqueous solutions with higher water ratios (water:acetonitrile?80%) or acidic solutions, fs-TA studies found that after the irradiation of KP the singlet state will transform into the triplet state with a high efficiency through an intersystem crossing and a triplet state mediated decarboxylation reaction of KP is confirmed in water-rich and acidic solutions as well as the triplet state KP- anion generating a KP carbanion through a decarboxylation reaction. Triplet state ketoprofen (3KP) is firstly observed by ns-TR3 experiments and then excited triplet state intramolecular proton transfer (ESIPT) induces 3KP to facilely undergo the decarboxylation reaction to generate a triplet protonated carbanion biradical (3BCH) species, this observation is also confirmed by the results from density functional theory (DFT) calculations. For solutions with higher water concentrations (such as between 50% and 90% water by volume), the hydrogen abstraction and decarboxylation processes are two competitive pathways with different rate constants. For KP-purine dyads, intramolecular hydrogen abstraction has been proposed to form ketyl-C1 biradical in acetonitrile solvent. Fs-TA study on KP-purine nucleoside dyads reveals that 3KP of cisoid dyads decays faster than 3KP of transoid dyads obtained in acetonitrile-water mixtures. Ns-TR3 experiments and DFT calculations suggest that ketyl-C1 biradical intermediate is generated with a higher efficiency for the 5-KP-dG dyad than for the 5-KP-dA and 5-KPGly-dA dyads. There is no ketyl-C1 biradical observed in ns-TR3 experiments for the 3-KP-dA dyad with transoid structure due to a steric effect. For FA, a solvent dependent photochemistry is observed. A typical nπ* triplet state FA (3FA) is evolved by a high efficient intersystem crossing in acetonitrile-rich solutions and subsequently 3FA promptly abstracts a hydrogen from water molecule to generate a ketyl radical intermediate. In contrast, an inversion of the hydrogen abstraction and decarboxylation reactions of nπ* 3FA is rationalized with the assistance of water molecules when going from acetonitrile-rich to water-rich mixtures. However, in 50% PBS solution, FA carbanion is observed from the picosecond to nanosecond times and the cleavage of FA carbanion gives rise to the enolate 3- anion at later nanosecond delay times.<br>published_or_final_version<br>Chemistry<br>Doctoral<br>Doctor of Philosophy

Palladium complexes have the ability to catalyse cross-coupling of two organic moieties through the formation of transient metal-carbon bonds, thus bringing them closer to each other to facilitate the formation of a new bond. Palladium-catalysed coupling reactions are one of the most important carbon-carbon forming reactions available to organic chemists and many of these reactions rely on the reactivity of aryl-palladium complexes. The investigation of new aryl-palladium precursors is thus of great interest, especially as more sustainable and economic methods can be developed. This thesis describes the use of carboxylic acids and sodium arylsulfinates as such new arylating agents. Protocols for microwave-assisted palladium(II)-catalysed decarboxylative synthesis of electron-rich styrenes and 1,1-diarylethenes were developed. However, these transformations had very limited substrate scopes which prompted the investigation of sodium arylsulfinates as alternative arylating agents. These substrates were employed in the microwave-assisted palladium(II)-catalysed desulfitative addition to nitriles, and the substrate scope was demonstrated by combining a wide array of sodium arylsulfinates and nitriles to yield the corresponding aryl ketones. The application of the desulfitative reaction in a continuous flow setup was demonstrated, and aluminium oxide was identified as safe alternative to borosilicate glass as a reactor material. The mechanisms of the decarboxylative and desulfitative transformations were investigated by density functional theory (DFT) calculations. The desulfitative reaction was also investigated by direct electrospray ionization mass spectrometry (ESI-MS), providing further mechanistic insight. Finally, a protocol for the safe and convenient synthesis of a wide range of sodium arylsulfinates was developed.