Total synthesis of (±)-paroxetine by diastereoconvergent cobalt-catalysed arylation

A total synthesis of paroxetine is reported, with a diastereoselective and diastereoconvergent cobalt-catalysed sp3–sp2 coupling reaction involving a 3-substituted 4-bromo-N-Boc-piperidine (Boc = tert-butoxycarbonyl) substrate as a key step. A 9:1 diastereoselectivity was obtained, while a control experiment involving a conformationally locked 3-substituted 4-bromo-tert-butyl cyclohexane ring proceeded with essentially complete stereoselectivit

A sea spray generation function for fetch-limited conditions

International audienceThis paper presents a sea spray generation function for aerosols produced by bubbles bursting that accounts for the effects of fetch. This is achieved by introducing a fetch-dependent model for the whitecap fraction, which is valid for fetch-limited conditions, i.e. steady-state conditions of the wave field in the whitecap droplet flux derived by Monahan et al. (1986). The aerosol generation fluxes calculated by this method show an enhancement of the aerosol production with increasing fetch. However, the predicted generation fluxes are lower than those calculated by using the classical model for the whitecap fraction proposed by Monahan and O'Muircheartaigh (1980). The results are then compared to aerosol size distributions measured in a Mediterranean coastal site at various fetch lengths. The data confirm the role of fetch, through its influence on marine aerosol generation and subsequent particle dispersion. The aerosol size distributions are divided into "fine" and "coarse" fractions. Submicrometer particles decrease in concentration at larger fetch, while the concentrations of super micron aerosols increase with increasing fetch

Cleaning graphene : a first quantum/classical molecular dynamics approach

Graphene outstanding properties created a huge interest in the condensed matter community and unprecedented fundings at the international scale in the hope of application developments. Recently, there have been several reports of incomplete removal of the polymer resists used to transfer as-grown graphene from one substrate to another, resulting in altered graphene transport properties. Finding a large-scale solution to clean graphene from adsorbed residues is highly desirable and one promising possibility would be to use hydrogen plasmas. In this spirit, we couple here quantum and classical molecular dynamics simulations to explore the kinetic energy ranges required by atomic hydrogen to selectively etch a simple residue, a CH3 group, without irreversibly damaging the graphene. For incident energies in the 2-15 eV range, the CH3 radical can be etched by forming a volatile CH4 compound which leaves the surface, either in the CH4 form or breaking into CH3+H fragments, without further defect formation. At this energy, adsorption of H atoms on graphene is possible and further annealing will be required to recover pristine graphene.Comment: 9 figures, 27 page

Diversité génétique de l’allèle O dans des populations berbères

Nous avons analysé le polymorphisme de l’allèle O chez 33 individus non apparentés de phénotype O d’une population berbère de l’oasis de Siwa en Égypte. Malgré le faible nombre d’individus étudiés, les résultats montrent un polymorphisme important de l’allèle O. Cette population a probablement eu des contacts avec d’autres populations malgré son isolement géographique. Siwa fut une étape importante pour les caravanes parcourant le désert ; elle fut soumise à de nombreux raids et conflits. Les fréquences des allèles O01 et O02 sont similaires à celles retrouvées dans une population berbère de l’Atlas marocain (Amizmiz). Trois nouveaux allèles ont été mis en évidence dans la population de Siwa. Ces résultats confirment tout l’intérêt d’étudier le polymorphisme moléculaire de l’allèle O pour mieux comprendre l’histoire génétique des populations.We analysed the O allele polymorphism in a sample of 33 Berbers from the Siwa population, all of them of phenotype O and unrelated to one another. The results show an important genetic diversity considering the limited number of individuals under study. The population must have been in contact with other people in spite of the geographical and cultural isolation. Siwa was an important stopping place for caravans in the desert: it was subjected to many raids and armed conflicts. The frequencies of the O01 and O02 alleles are similar to those in the Amizmiz Berbers in Morocco. Three new alleles were discovered in the Siwa population. These results confirm the importance of studying the molecular polymorphism of the O allele to better understand the genetic history of populations

Concepts, Capabilities, and Limitations of Global Models : A Review

International audienceFor researchers wishing to generate an understanding of complex plasma systems, global models often present an attractive first step, mainly due to their ease of development and use. These volume averaged models are able to give descriptions of plasmas with complex chemical kinetics, and without the computationally intensive numerical methods required for spatially resolved models. This paper gives a tutorial on global modeling, including development and techniques, and provides a discussion on the issues and pitfalls that researchers should be aware of. Further discussion is provided in the form of two reviews on methods of extending global modeling techniques to encompass variations in either time or space

Graphenes in the absence of metals as carbocatalysts for selective acetylene hydrogenation and alkene hydrogenation

Catalysis makes possible a chemical reaction by increasing the transformation rate. Hydrogenation of carbon-carbon multiple bonds is one of the most important examples of catalytic reactions. Currently, this type of reaction is carried out in petrochemistry at very large scale, using noble metals such as platinum and palladium or first row transition metals such as nickel. Catalysis is dominated by metals and in many cases by precious ones. Here we report that graphene (a single layer of one-atom-thick carbon atoms) can replace metals for hydrogenation of carbon-carbon multiple bonds. Besides alkene hydrogenation, we have shown that graphenes also exhibit high selectivity for the hydrogenation of acetylene in the presence of a large excess of ethylene.This study was financially supported by the Spanish Ministry of Economy and Competitiveness (Severo Ochoa and CTQ2012-32315); and Generalidad Valenciana (Prometeo 21/013) is gratefully acknowledged.Primo Arnau, AM.; Neatu, F.; Florea, M.; Parvulescu, V.; García Gómez, H. (2014). Graphenes in the absence of metals as carbocatalysts for selective acetylene hydrogenation and alkene hydrogenation. Nature Communications. 5:1-9. https://doi.org/10.1038/ncomms6291S195Dreyer, D. R. & Bielawski, C. W. Carbocatalysis: heterogeneous carbons finding utility in synthetic chemistry. Chem. Sci. 2, 1233–1240 (2011).Machado, B. F. & Serp, P. Graphene-based materials for catalysis. Catal. Sci. Technol. 2, 54–75 (2012).Schaetz, A., Zeltner, M. & Stark, W. J. Carbon modifications and surfaces for catalytic organic transformations. 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Reduced graphene oxide for catalytic oxidation of aqueous organic pollutants. ACS Appl. Mater. Interf. 4, 5466–5471 (2012).Dreyer, D. R., Jia, H. P. & Bielawski, C. W. Graphene oxide: a convenient carbocatalyst for facilitating oxidation and hydration reactions. Angew. Chem. Int. Ed. 49, 6813–6816 (2010).Dreyer, D. R., Jia, H. P., Todd, A. D., Geng, J. X. & Bielawski, C. W. Graphite oxide: a selective and highly efficient oxidant of thiols and sulfides. Org. Biomol. Chem. 9, 7292–7295 (2011).Hayashi, M. Oxidation using activated carbon and molecular oxygen system. Chem. Rec. 8, 252–267 (2008).Jia, H. P., Dreyer, D. R. & Bielawski, C. W. C-H oxidation using graphite oxide. Tetrahedron 67, 4431–4434 (2011).Kumar, A. V. & Rao, K. R. Recyclable graphite oxide catalyzed Friedel-Crafts addition of indoles to alpha, beta-unsaturated ketones. Tetrahedron Lett. 52, 5188–5191 (2011).Soria-Sanchez, M. et al. Carbon nanostructure materials as direct catalysts for phenol oxidation in aqueous phase. Appl. Catal. B Environ. 104, 101–109 (2011).Verma, S. et al. Graphene oxide: an efficient and reusable carbocatalyst for aza-Michael addition of amines to activated alkenes. Chem. Commun. 47, 12673–12675 (2011).Yu, H. et al. Solvent-free catalytic dehydrative etherification of benzyl alcohol over graphene oxide. Chem. Phys. Lett. 583, 146–150 (2013).Holschumacher, D., Bannenberg, T., Hrib, C. G., Jones, P. G. & Tamm, M. Heterolytic dihydrogen activation by a frustrated carbene-borane Lewis pair. Angew. Chem. Int. Ed. 47, 7428–7432 (2008).Staubitz, A., Robertson, A. P. M., Sloan, M. E. & Manners, I. Amine- and phosphine-borane adducts: new interest in old molecules. Chem. Rev. 110, 4023–4078 (2010).Stephan, D. W. & Erker, G. Frustrated Lewis Pairs: Metal-free Hydrogen Activation and More. Angew. Chem. Int. Ed. 49, 46–76 (2010).Poh, H. L., Sanek, F., Sofer, Z. & Pumera, M. High-pressure hydrogenation of graphene: towards graphane. Nanoscale 4, 7006–7011 (2012).Sofo, J. O., Chaudhari, A. S. & Barber, G. D. Graphane: A two-dimensional hydrocarbon. J. Phys. Chem. B 75, 153401 (2007).Elias, D. C. et al. Control of graphene’s properties by reversible hydrogenation: evidence for graphane. Science 323, 610–613 (2009).Despiau-Pujo, E. et al. Elementary processes of H2 plasma-graphene interaction: a combined molecular dynamics and density functional theory study. J. Appl. Phys. 113, 114302 (2013).Xu, L. & Ge, Q. Effects of defects and dopants in graphene on hydrogen interaction in graphene-supported NaAlH4. Int. J. Hydrogen Energy 38, 3670–3680 (2013).Perhun, T. I., Bychko, I. B., Trypolsky, A. I. & Strizhak, P. E. Catalytic properties of graphene material in the hydrogenation of ethylene. Theor. Exp. Chem. 48, 367–370 (2013).Hummers, W. S. & Offeman, R. E. Preparation of graphitic oxide. J. Am. Chem. 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The roles of subsurface carbon and hydrogen in palladium-catalyzed alkyne hydrogenation. Science 320, 86–89 (2008).Bridier, B., Lopez, N. & Perez-Ramirez, J. Molecular understanding of alkyne hydrogenation for the design of selective catalysts. Dalton Trans. 39, 8412–8419 (2010).Flick, K., Herion, C. & Allmann, H. Palladium-haltiger Trägerkatalysator zur selektiven katalytischen Hydrierung von Acetylen in Kohlenwasserstoffströmen. EP764463-A; EP764463-A2; DE19535402-A1; JP9141097-A; CA2185721-A; KR97014834-A; MX9604031-A1; US5847250-A; US5856262-A; TW388722-A; MX195137-B; CN1151908-A; EP764463-B1; DE59610365-G; ES2197222-T3; KR418161-B; CN1081487-C; JP3939787-B2; CA2185721-C (1997).Gartside, R. J. et al. Improved olefin plant recovery system employing a combination of catalytic distillation and fixed bed catalytic steps. 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A short total synthesis of (±)-paroxetine and a formal asymmetric synthesis of (–)-paroxetine

Paroxetine, a selective serotonin reuptake inhibitor, is a potent drug used for the treatment of depression for more than 20 years. Although numerous syntheses have been reported for this molecule, the manufacturing process still uses a resolution step, as it remains the shortest way to access paroxetine on a large scale.Our synthesis of paroxetine offers an alternative solution, delivering the final compound in only six steps from commercially available material. This has been possible thanks to the use of both organo- and organometallic catalysis to introduce the two chiral centres. Formaldehyde has been used in a direct proline-catalysed aldol reaction, allowing the selective introduction of a hydroxymethyl group with good atom economy. Optimisation of a cobalt-catalysed Kumada-type Csp3-Csp2 cross coupling reaction on a secondary bromide enabled us to introduce the aryl substituent in the 4-position. Furthermore, the generation of a configurationally labile cobalt intermediate in the cross coupling reaction has been successfully exploited to develop a diastereoselective arylation. The use of methanol for the introduction of a hydroxymethyl group via transfer hydrogenative coupling has also been briefly investigated for incorporation in an asymmetric synthesis of abacavir