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Producción Científica, Developing new procedures for the synthesis of tetrahydropyrans in a very stereoselective manner is of great importance for the synthesis of THP-containing natural products. Here, we report an interesting protocol for the synthesis of polysubstituted halogenated tetrahydropyrans by silyl-Prins cyclization of vinylsilyl alcohols, in which the nature of the Lewis acid determines the outcome of the process. The methodology has been applied to the synthesis of a known antinociceptive., Junta de Castilla y León (VA294P18)

The introduction of thiophene rings to the helical structure of carbohelicenes has electronic effects that may be used advantageously in organic electronics. The performance of these devices is highly dependent on the sulfur atom topology, so a precise knowledge of the synthetic routes that may afford isomeric structures is necessary. We have studied the photocyclization pathway of both 2- and 3-styrylthiophenes on their way to thiahelicenes by experiment and theory. To begin with, the synthesis of stereochemically well-defined 2- and 3-styrylthiophenes allowed us to register first, and simulate later, the UV–vis electronic spectra of these precursors. This information gave us access through time-dependent density functional theory calculations to the very nature of the excited states involved in the photocyclization step and from there to the regio- and stereochemical outcome of the reaction. For the widely known case of a 2-styrylthiophene derivative, the expected naphtho[2,1-b]thiophene type of ring fusion was predicted and experimentally observed by synthesis. On the contrary, 3-styrylthiophene derivatives have been seldom used in synthetic photocyclizations. Among the two possible structural outcomes, only the naphtho[1,2-b]thiophene type of ring fusion was found to be mechanistically sound, and this was actually the only compound observed by synthesis. Financial support by the Spanish Ministerio de Economía y Competitividad (MAT2016-78625-C2-2-P), the Ministerio de Ciencia, Innovación y Universidades (PID2019-109539GB-C4 and PGC2018-096955-B-C44), the Generalitat Valenciana (PROMETEO/2017/139), and finally, the University of Alicante (VIGROB-285) is gratefully acknowledged. The computational resources provided by the Department of Applied Physics of the University of Alicante are greatly appreciated.

The synthesis of three novel families of pyrrolo[2,1-c][1,4]benzodiazepine-5-ones is described. The compounds were prepared according to a three-step sequence, involving an Ugi reaction, building of the pyrrolo nucleus, and reduction–cyclization to the corresponding diazepine. Depending on the amine employed in the synthesis of the Ugi adducts, different unsaturation degrees could be obtained in the pyrrolo ring (saturated or with endo or exo unsaturations), a key feature determining their biological activity, as it affects the affinity of the pyrrolobenzodiazepines toward DNA and thus their cytotoxicity. This synthetic methodology represents a significant improvement with respect to those described in the literature so far, as it uses inexpensive and commercially available starting materials without needing derivatization or the use of protecting groups., Consejería de Educación de la Junta de Castilla y León (project BU075G19)

Peptides are well-known to play a fundamental therapeutic role and to represent building blocks for numerous useful biomaterials. Stabilizing their active 3D-structure by appropriate modifications remains, however, a challenge. In this study, we have expanded the available literature information on the conformational propensities of a promising backbone change of a terminally blocked delta-amino acid residue, a dipeptide mimic, by replacing its central amide moiety with an (E) C(beta)=C(gamma) alkene unit. Specifically, we have examined by DFT calculations, X-ray diffraction in the crystalline state, and FT-IR absorption/NMR spectroscopies in solution the extended vs folded preferences of analogues of this prototype system either unmodified or possessing single or multiple methyl group substituents on each of its four -CH2-CH=CH-CH2- main-chain carbon atoms. The theoretical and experimental results obtained clearly point to the conclusion that increasing the number of adequately positioned methylations will enhance the preference of the original sequence to fold, thus opening interesting perspectives in the design of conformationally constrained peptidomimetics.

The photochemical behavior of several dienones was studied under aerobic conditions. 2-Allylidene-1,3-cycloalkanediones prepared via Knoevenagel-type condensation between simple readily available 1,3-dicarbonyl substrates and á,â-unsaturated aldehydes afforded 1,2,4-trioxane derivatives upon UVA irradiation in the presence of oxygen. This domino self-sensitized photooxygenation cascade of conjugated carbonyl systems proceeds stereoselectively and involves the formation of two new oxa-cycles, three new bonds (two C-O), and three stereocenters. Fil: Riveira, Martín Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Martiren, Nadia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Mischne, Mirta Paulina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina

The addition of 2-bromobenzylmagnesium bromide to chiral N-tert-butanesulfinyl imines derived from tetralone-type ketones proceeds with high levels of diastereocontrol. The resulting sulfinamide derivatives were transformed into dibenzoazaspiro compounds after a palladium-catalyzed intramolecular N-arylation. DFT calculations have been performed to rationalize the stereochemical course of the reaction. Similar results have been obtained considering either diethyl ether or toluene as a solvent, in both cases in an excellent agreement with experimental findings. NCI topological calculations have also been used to evidence crucial noncovalent interactions. In addition, the azaspiro compounds reduced the viability of chronic myeloid leukemia cells in the micromolar range. Notably, both the halogen-substituted (R)- and (S)-8g and -8h as well as (R)-8j were at least two times more effective on a multidrug-resistant derivative than on the parental cell line, exerting a collateral sensitivity effect. We acknowledge the continued financial support from the Spanish Ministerio de Economía y Competitividad (MINECO; project CTQ2014-53695-P, CTQ2014-51912-REDC, CTQ2016-81797-REDC, CTQ2016-76155-R, CTQ2017-85093-P), FEDER, the Generalitat Valenciana (PROMETEOII/2014/017), and the University of Alicante. We thankfully acknowledge the resources from the supercomputers “Memento” and “Cierzo” and technical expertise and assistance provided by BIFI-ZCAM (Universidad de Zaragoza, Spain). We also thank Prof. Vivian M. Rumjanek for providing FEPS cells and Prof. Adriano D. Andricopulo for the preliminary cytotoxicity screening. This study was also financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001.

A simple one-pot protocol for the synthesis of fused pyrrolopiperazines with a complete diastereoselectivity has been developed. This novel methodology combined the Ugi reaction with a spontaneous enamine alkylation on a multicomponent domino reaction, starting from nonprotected diamines and arylglyoxals., Consejerıá de Educacioń de la Junta de Castilla y León (project BU075G19)

A DFT study of the mechanism of the Borono-Mannich reaction using benzylamine and piperidine as representative examples of primary and secondary amines with pinacol allenylboronate is presented. The study shows that both reactions progress through coordination between the boron and the phenolic oxygen. Ring size strain and hydrogen bond activation appear to determine the observed divergent regioselectivity. In the case of benzylamine, the eight-membered ring transition structure that leads to the propargylamine exhibits a hydrogen bond between the hydrogen attached to the nitrogen and the phenolic oxygen, whereas for piperidine a hydrogen bond between the hydrogen on the imine carbon and one of the oxygens of the pinacol group was observed in the six-membered ring transition structure toward the allenylamine. Fil: Simonetti, Sebastián Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Pellegrinet, Silvina Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina

Imidoyl sulfoxonium ylides are presented for the first time as potential precursors to generate α-imino metal-carbene intermediates and applied in direct C-H functionalization reactions catalyzed by [Ir(cod)Cl]2 (4 mol %) to provide 2-substituted indoles (up to 70% yield) in just one step. This class of sulfur ylide is successfully obtained from imidoyl chloride and dimethylsulfoxonium methylide (23 new examples in 45-85% yield) or by imino group formation from the corresponding β-keto sulfoxonium ylides and anilines in the presence of TiCl4 as a Lewis acid (9 examples in 33-94% yield).

The straightforward oxidation of electron-rich arenes, namely, phenols, naphthols, and anisole derivatives, under mild reaction conditions, is described by means of the use of an environmentally benign HFIP-UHP system. The corresponding quinones or hydroxylated arenes were obtained in moderate to good yields. We would like to thank the Spanish Ministerio de Economía, Industria y Competitividad (CTQ2015-66624-P and CTQ2017-88171-P), Spanish Ministerio de Ciencia, Innovación y Universidades (PGC2018-096616-B-I00), and the University of Alicante (UADIF17-27, VIGROB-285 and VIGROB-316) for the financial support.

A tandem process of ring-closing enyne metathesis (RCEYM)-reduction using modern ruthenium catalysts and a hydrogen donor is described. This straightforward methodology is useful for C(sp3) generation under mild reaction conditions. Variables such as solvent, catalyst, hydride source, and temperature were adjusted toward the exclusive formation of different products. Fil: Prada Gori, Denis Nihuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Permingeat Squizatto, Caterina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Cornier, Patricia Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Delpiccolo, Carina Maria Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina

[EN] Cholesterol (Ch) is an integral part of cell membrane, where it is prone to oxidation. In humans, oxidation of Ch is commonly linked to various pathologies like Alzheimer's disease, atherosclerosis, and even cancer, which proceed via mechanisms involving enzymatic and free radical pathways. The latter begin with hydrogen abstraction (HA) from Ch by a reactive free radical. It has been established that the most efficient HA from Ch occurs at C7, although HA from C4 by peroxyl radicals has recently been observed. Conversely, HA from Ch positions other than the thermodynamically preferred C7 or C4 has never been reported. We have designed a Ch derivative where a benzophenone moiety is linked to C7 by a covalent bond. This mirrors a specific orientation of Ch within a confined environment. Product analysis and time-resolved spectroscopic studies reveal an unprecedented HA from C15, which is a thermodynamically unfavorable position. This indicates that a specific topology of reactants is crucial for the reactivity of Ch. The relative orientation of the reactants can also be relevant in biological membranes, where Ch, polyunsaturated fatty acids, and numerous oxidizing species are confined in highly restricted and anisotropic environments., This work was supported by the Carlos III Institute of Health (Grants No. PII6/01877, "Miguel Servet fellowship" CPII16/00052 to I.A.), and by the Generalitat Valenciana (Prometeo 2017/075). We would like to thank Dr Fedora Grande for sending an exchange student (M.B.). D.N. and G.G. thank NAWI Graz for support.

[EN] An asymmetric catalytic reaction of hydroxyindoles with nitroalkenes leading to the Friedel-Crafts alkylation in the carbocyclic ring of indole is presented. The method is based on the activating/directing effects of the hydroxy group situated in the carbocyclic ring of the indole providing nitroalkylated indoles functionalizated at the C-4, C-5, and C-7 positions with high yield, regio-, and enantioselectivity. The optically enriched nitroalkanes were transformed efficiently in optically enriched 2-amino-1,1-diarylalkanes bearing a carbocyclic ring substituted indole., Financial support from the MINECO (Gobierno de Espana; CTQ2017-84900-P) is gratefully acknowledged. C.V. thanks MINECO for a JdC contract. J.R.-B. thanks the Ministry of Education for a Collaboration grant. Access to NMR, MS, and X-ray facilities from the Servei Central de Suport a la Investigacio Experimental (SCSIE)-UV is also acknowledged

The photolysis of triethylamine (1a) in the presence of carbon dioxide leads to the hydrogenation of CO2, the α-C-C coupling of triethylamine (1a), and the CO2-insertion into the α-C-H σ-bond of amine 1a. This reaction is proposed to proceed through the radical ion pair [R3N·+·CO2·-] generated by the photoionization of amine 1a and the electron capture by CO2. The presence of lithium tetrafluoroborate in the reaction medium promotes the efficient and stereoselective α-C-C coupling of 1a by enhancing the production of α-dialkylamino radicals and the isomerization of N,N,N',N'-tetraethylbutane-2,3-diamine (4a).

Stimulated by its success in both bioconjugation and surface modification, we studied the strain-promoted oxidation-controlled cycloalkyne–1,2-quinone cycloaddition (SPOCQ) in three ways. First, the second-order rate constants and activation parameters (ΔH⧧) were determined of various cyclooctynes reacting with 4-tert-butyl-1,2-quinone in a SPOCQ reaction, yielding values for ΔH⧧ of 4.5, 7.3, and 12.1 kcal/mol, for bicyclo[6.1.0]non-4-yne (BCN), cyclooctyne (OCT), and dibenzoazacyclooctyne (DIBAC), respectively. Second, their reaction paths were investigated in detail by a range of quantum mechanical calculations. Single-configuration theoretical methods, like various DFT and a range of MP2-based methods, typically overestimate this barrier by 3–8 kcal/mol (after inclusion of zero-point energy, thermal, and solvation corrections), whereas MP2 itself underestimates the barrier significantly. Only dispersion-corrected DFT methods like B97D (yielding 4.9, 6.4, and 12.1 kcal/mol for these three reactions) and high-level CCSD(T) and multireference multiconfiguration AQCC ab initio approaches (both yielding 8.2 kcal/mol for BCN) give good approximations of experimental data. Finally, the multireference methods show that the radical character in the TS is rather small, thus rationalizing the use of single-reference methods like B97D and SCS-MP2 as intrinsically valid approaches.

Primary allylic amines with enantiomeric excesses from 97 to >99% were prepared by asymmetric transfer hydrogenation of α,β-unsaturated N-(tert-butylsulfinyl)ketimines followed by removal of the sulfinyl group. The effect caused by different substituents at the C═C bond and at the iminic carbon atom on the chemoselectivity of the reduction was studied. The desired enantiomer of the final allylic amine can be synthesized by choosing the sulfinyl group with the appropriate absolute configuration. This work was generously supported by the Spanish Ministerio de Ciencia e Innovación (MICINN; Grant CTQ2011-24151), the Spanish Ministerio de Economía, Industria y Competitividad (Grant CTQ2015-66624-P), and the University of Alicante. E.S. thanks the University of Alicante for a predoctoral fellowship. O.P. thanks the Spanish Ministerio de Educación for a predoctoral fellowship (Grant AP-2008-00989).

Diastereoselective multicomponent reactions of enantioenriched 4-nitroprolinates, obtained by enantiocatalyzed 1,3-dipolar cycloaddition (1,3-DC) of imino esters and nitroalkenes, with α,β-unsaturated aldehydes and electrophilic alkenes proceed with total periselectivity depending on the structure of the aldehyde employed. This process evolves through a [3 + 2] 1,3-DC when cinnamaldehyde is used in the presence of an azomethine ylide, giving the corresponding highly substituted pyrrolizidines with endo selectivity. However, in the case of the α,β-unsaturated aldehyde, which contains a hydrogen atom at the γ position, an amine–aldehyde–dienophile (AAD) [4 + 2] cycloaddition takes place by formation of an intermediate 1-amino-1,3-diene, affording highly functionalized cyclohexenes with high endo diastereoselectivity. This AAD process only occurred when a nitro group is bonded to the 4-position of the initial enantiomerically enriched pyrrolidine ring. DFT calculations have been carried out with the aim of explaining this different behavior between pyrrolidines with or without a nitro group, demonstrating the strong nitro-group-dependent periselectivity. The results of these computational studies also support the experimentally obtained absolute configuration of the final adducts. Financial support was provided by the Spanish Ministerio de Ciencia e Innovación (MICINN) (projects CTQ2010-20387, and Consolider Ingenio 2010, CSD2007-00006), the Spanish Ministerio de Economía y Competitividad (MINECO) (projects CTQ2013-43446-P and CTQ2014-51912-REDC), the Spanish Ministerio de Economía, Industria y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, EU) (projects CTQ2016-76782-P, CTQ2016-80375-P, and CTQ2016-81797-REDC), the Generalitat Valenciana (PROMETEO 2009/039 and PROMETEOII/2014/017), the University of Alicante, the Gobierno Vasco/Eusko Jaurlaritza (Grant IT673-13), and the University of the Basque Country UPV/EHU (UFI11/22 QOSYC). O.L. gratefully acknowledges the UPV/EHU for her postdoctoral grant.

The diastereoselective synthesis of cis and trans steroid-fulleropyrrolidines hybrids by reaction of N-metalated azomethine ylides [Cu(II) or Ag(I)] with the appropriate chiral ligand and C60 is described. The experimental findings reveal that the azomethine ylide stabilized by an allylic group cycloadds to [60]fullerene in an efficient manner and with a good diastereomeric excess. Furthermore, the new generated stereocenters are fully controlled by the catalytic systems used without being influenced by the chirality of the steroid. Interestingly, by this synthetic methodology the each one of the four possible stereoisomers have efficiently been obtained and characterized by CD spectra.

Palladium-catalyzed aminocarbonylation reactions have been used to directly convert a tetraiodocavitand intermediate into the corresponding carboxamides and 2-ketocarboxamides. When complex mixtures of the amine reactants are employed in competition experiments, no ‘mixed’ products possessing structurally different amide fragments are detected either by 1H or 13C NMR. Only highly symmetrical cavitands are sorted out of a large number of potentially feasible products, which represents a rare example of intramolecular, narcissistic self-sorting. The reactivity order of the amine reactants and the changes in the Gibbs energies calculated using the semiempirical PM6 model suggest that this self-sorting process is kinetically controlled.

Isatin in a solution of dry N,N-dimethylformamide/NaClO4 is electroreduced in the presence of CH3I. N-methylisatin (NMI) is obtained in quantitative molar yield and high current efficiency by controlled potential electrolysis (CPE). NMI and N-methylisatoic anhydride are the reaction products when CPE is performed in the absence of CH3I, but adding it once the CPE was completed. The water effect on the identity and yield of the reaction product(s) is investigated. Reaction pathways are proposed. Fil: Martinez Suarez, Jaime Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Caram, José Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina Fil: Echeverría, Gustavo Alberto. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina Fil: Piro, Oscar Enrique. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina Fil: Gennaro, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Física del Litoral. Universidad Nacional del Litoral. Instituto de Física del Litoral; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina Fil: Mirifico, Maria Virginia. Universidad Nacional de La Plata. Facultad de Ingenierí­a. Departamento de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina

[EN] The first enantioselective formal [3 + 2] cycloaddition between ¿-isocyanoesters and trifluoromethylketones to give 5-trifluoromethyl-2-oxazolines bearing two contiguous stereogenic centers, one of them being a quaternary stereocenter substituted with a CF3 group, has been developed. The reaction is based upon a multicatalytic approach that combines a bifunctional Brønsted base-squaramide organocatalyst and Ag+ as Lewis acid. The reaction could be achieved with a range of aryl and heteroaryl trifluoromethyl ketones, and the resulting oxazolines were obtained with good to excellent diastereo- and enantioselectivity., Financial support from the MINECO and FEDER (CTQ2017-84900-P). Access to NMR and MS facilities from SCSIE-UV. C.V. thanks the Spanish Government for a Ramon y Cajal contract (RyC-2016-20187). A.S.-M. thanks the Generalitat Valenciana and Fondo Social Europeo for a postdoctoral grant (APOST/2016/139).

The first catalytic enantioselective pinacol rearrangement was reported by Antilla and co-workers in 2010. The reaction was catalyzed by a chiral phosphoric acid and resulted in high levels of enantioselectivity (up to 96% ee). The present study uses density functional theory to investigate the mechanism and origins of stereoselectivity of this important reaction and to explain the difference in selectivity between different catalysts. An OH···O hydrogen bond between the intermediate indolyl alcohol and the phosphate group from the catalyst together with a CH···O hydrogen bond between the indole and the phosphate group were observed in the preferred activation mode for the stereodetermining [1,2]-aryl shift. A stronger CH···O interaction in the major transition state was found to contribute to the high levels of enantioselectivity. A more bulky catalyst (TRIP) was found to impede the formation of the key CH···O interaction, leading to lower levels of enantioselectivity. Fil: Falcone, Bruno Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina Fil: Grayson, Matthew N.. University Of Bath; Reino Unido Fil: Rodriguez, Juan Bautista. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina

[EN] Latent electrophiles are nowadays very attractive chemical entities for drug discovery, as they are unreactive unless activated upon binding with the specific target. In this work, the utility of 4-trifluoromethyl phenols as precursors of latent electrophiles, quinone methides (QM), for lysine-targeting is demonstrated. These Michael acceptors were photogenerated for specific covalent modification of lysine residues using human serum albumin (HSA) as a model target. The reactive QM-type intermediates I or II, generated upon irradiation of 4-trifluoromethyl-1-naphthol (1)@HSA or 4-(4-trifluorometylphenyl)phenol (2)@HSA complexes, exhibited chemoselective reactivity toward lysine residues leading to amide adducts, which was confirmed by proteomic analysis. For ligand 1, the covalent modification of residues Lys106 and Lys414 (located in subdomains IA and IIIA, respectively) was observed, whereas for ligand 2, the modification of Lys195 (in subdomain IIA) took place. Docking and molecular dynamics simulation studies provided an insight into the molecular basis of the selectivity of 1 and 2 for these HSA subdomains and the covalent modification mechanism. These studies open the opportunity of performing protein silencing by generating reactive ligands under very mild conditions (irradiation) for specific covalent modification of hidden lysine residues., Financial support from the Spanish Ministry of Economy and Competiveness [CTQ2016-78875-P, SAF2016-75638-R and BES-2014-069404 (predoctoral fellowship to O.M.-M.)], the Generalitat Valenciana (PROMETEO/2017/075), the Community of Madrid (2016-T1/AMB-1275), the Xunta de Galicia (Centro Singular de Investigacion de Galicia accreditation 2016-2019, ED431G/09 and postdoctoral fellowship to E.L.), and the European Union (European Regional Development Fund, ERDF) is gratefully acknowledged. The proteomic analysis was performed in the proteomics facility of SCSIE University of Valencia that belongs to ProteoRed PRB2-ISCIII and is supported by grant PT13/0001, of the PE I+D+i 2013-2016, funded by ISCIII and FEDER. We are grateful to the Centro de Supercomputacion de Galicia (CESGA) for use of the Finis Terrae computer.

The chemical fate of radical intermediates is relevant to understand the biological effects of radiation and to explain formation of DNA lesions. A direct approach to selectively generate the putative reactive intermediates is based on the irradiation of photolabile precursors. But, to date, radical formation and reactivity have only been studied in aqueous media, which do not completely mimic the micro environment provided by the DNA structure and its complexes with proteins. Thus, it is also important to evaluate the photogeneration of nucleoside-based radicals in nonaqueous media. The attention here is focused on the independent generation of 5,6-dihydropyrimidin-5-yl radicals in organic solvent through the synthesis of new lipophilic tert-butyl ketone precursors. Formation of 5,6-dihydro-2'-deoxyuridin-S-yl and 5,6-dihydrothymidin-5-yl radicals has first been confirmed by using a new nitroxide-derived profluorescent radical trap. Further evidence has been obtained by nanosecond laser flash photolysis through detection of long-lived transients. Finally, the experimental data are corroborated by multiconfigurational ab initio CASPT2//CASSCF methodology., Spanish Government (CTQ2012-32621, CTQ2015-70164-P, CTQ2014-58624-P, RIRAAF RETICS RD12/0013/0009, Severo Ochoa program/SEV-2012-0267, Maria de Maetzu program/MDM-2015-0538, BES-2011-048326 and BES-2013-066566, JCI-2012-13431) and Generalitat Valenciana (Prometeo 11/2013/005 and GV2015-057) are gratefully acknowledged. Dr. M. Luisa Marin is also acknowledged for her help during laser flash photolysis experiments.

A successful combination of computational chemistry and total synthesis was explored to tentatively elucidate the absolute configuration of cryptomoscatone E3, a polyketide isolated from the Brazilian tree Cryptocarya mandiocanna. Two independent synthetic approaches are discussed based on asymmetric allylation, ring closing metathesis, and aldol reactions. Fil: Novaes, Luiz F. T.. Universidade Estadual de Campinas; Brasil Fil: Sarotti, Ariel Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Pilli, Ronaldo A.. Universidade Estadual de Campinas; Brasil

An efficient methodology for the synthesis of a series of new fused polyclyclic indoles has been developed by Brønsted acidcatalyzed intramolecular Friedel−Crafts reactions of properly designed indolyl alcohols., Ministerio de Economiá y Competitividad (MINECO) and FEDER (CTQ2013-48937- C2-1-P) and Junta de Castilla y León (BU237U13)

The transition-metal-catalyzed [2 + 2 + 2]-cycloaddition of alkynes has become a powerful atom-economical strategy for aromatic ring construction. Unfortunately, the control of the stereo-, regio-, and chemoselectivity of these processes is usually challenging, and these reactions can potentially lead to complex unuseful mixtures. While solid-phase chemistry has proven to be a successful tool for decreasing the number of cycloadducts formed and for facilitating the purification step, an integral use of the outcoming products in this complex reaction is described herein. By using an immobilized monoalkyne, the transition-metal-catalyzed [2 + 2 + 2]-cycloaddition with soluble 1,6-diyne-esters led to the simultaneous preparation of soluble and solid-supported phthalides, showing a new way to benefit from solid-phase synthetic methodologies. Fil: Riveira, Martín Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Diez, Cintia Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Mischne, Mirta Paulina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Mata, Ernesto Gabino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina

The photochemical one-electron oxidation of alkyl aryl selenides was studied by means of laser flash photolysis (355 nm). Quenching of the sensitizers in their excited state leads to selenide radical cation in the presence of selenium derivatives. The π-type dimer of methyl phenyl selenide radical cation was detected at 630 nm at expenses of the monomeric radical cation (530 nm). The effect of modification of the aryl and alkyl substituents was also studied, resulting that the formation of dimers depends on both, the electronic properties and steric hindrance of the substituents. Both effects, an increase in steric hindrance in the alkyl moiety or the presence of strongly electron donor groups in the aromatic substituent that stabilizes the radical cation, prevent the dimer formation. Fil: Bouchet, Lydia María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Argüello, Juan Elias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina

A practical, integrated and versatile U-4CR-based assembly of 1,4-benzodiazepin-2-ones exhibiting functionally, skeletally, and stereochemically diverse substitution patterns is described. By virtue of its convergence, atom economy, and bond-forming efficiency, the methodology documented herein exemplifies the reconciliation of structural complexity and experimental simplicity in the context of medicinal chemistry projects. This work was financially supported by the Galician Government (Spain), Projects: 09CSA016234PR and GPC-2014-PG037. J.A. thanks FUNDAYACUCHO (Venezuela) for a predoctoral grant and Deputación da Coruña (Spain) for a postdoctoral research grant. A.N.-V. thanks the Spanish government for a Ramón y Cajal research contract.

The reaction of chiral N-tert-butanesulfinyl aldimines with β-keto acids under basic conditions at room temperature proceeds with high levels of diastereocontrol, leading to β-amino ketones in high yields. Based on DFT calculations, an eight-membered cyclic transition state involving coordination of the lithium atom to the oxygens of carboxylate and sulfinyl units was proposed, being in agreement with the observed experimental diastereomeric ratios. The synthesis of the piperidine alkaloid (−)-pelletierine was successfully undertaken in order to demonstrate the utility of this methodology. We thank the continued financial support from our Ministerio de Ciencia e Innovación (MCINN; projects CTQ2010-20387, CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24165), the Ministerio de Economía y Competitividad (MINECO; projects CTQ2014-53695-P, CTQ2016-80375-P, CTQ2014-51912-REDC, CTQ2016-81797-REDC), FEDER, the Generalitat Valenciana (PROMETEO 2009/039, PROMETEOII/2014/017), Gobierno Vasco/Eusko Jaurlaritza (Grant IT-324-07), and the University of Alicante.

The scandium triflate-catalyzed cycloaddition reaction of polycyclic 1,2-dithiolethiones to maleimides is described. The reaction constitutes an easy approach to linear as well as branched oligomeric cis-fused dihydro[1,3]dithiolo[4,5-c]pyrrole-4,6-dione rings interconnected by 3,5-diylidenethiomorpholine-2,6-dithione or ylidene-6-thioxo[1,2]dithiolo[3,4-b][1,4]thiazin-3-one groups. The presence of highly colored, highly polarized push−pull α,β- unsaturated thione groups in their structures make these compounds sensitive to the presence of mercury(II) cation in organic or mixed organic/aqueous solvents., Ministerio de Economía y Competitividad, Spain (Project CTQ2012- 31611), Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (Project BU246A12-1), and the European Commission Seventh Framework Programme (Project SNIFFER FP7-SEC-2012-312411).

The diastereoselective addition of an allylic indium intermediate to chiral o-bromophenyl sulfinyl imine 4 proceeded with good levels of diastereoselectivity. The resulting homoallylic amine derivatives were transformed into lactams 7 and 12, which upon copper-mediated intramolecular N-arylation led to the formation of benzo-fused 1-azabicyclo[j.k.0]alkanes 8 and 13. Benzo-fused 2-allyl-substituted heterocycles 14 could also be prepared by means of a palladium-catalyzed N-arylation of the corresponding free amines. The synthesis of the alkaloid (−)-angustureine was easily accomplished from (S)-2-allyltetrahydroquinoline (14b). Spanish Ministerio de Ciencia e Innovación (Grants CTQ2007-65218, Consolider Ingenio 2010-CSD-2007-00006, and CTQ2011-24165), the Generalitat Valenciana (Grant PROMETEO/2009/039 and FEDER), and the University of Alicante.

A convenient method for the preparation of synthetically useful 3- iodoindene derivatives has been developed. This protocol, based on the 5-endo iodocyclization reaction of o-(alkynyl)styrenes, represents one of the scarce examples of halocyclizations using olefins as nucleophilic counterparts and allows the synthesis of both 3-iodo-1H-indenes (from β-alkyl-β-alkyl/aryl-o-(alkynyl)styrenes) and 3-iodobenzofulvenes (from β,β-diaryl-o-(alkynyl)styrenes) in good yields under mild reaction conditions. In addition, related alkoxyiodocyclization processes are described, which are particularly interesting in their intramolecular version because they allow the synthesis of heteropolycyclic structures containing the indene core. Finally, the usefulness of the prepared 3-iodoindenes has been demonstrated by the synthesis of several polysubstituted indene derivatives through conventional palladium-catalyzed cross-coupling reactions and iodine−lithium exchange processes., Ministerio de Economiá y Competitividad (MINECO) and FEDER (CTQ2013-48937- C2-1P) and Junta de Castilla y León (BU237U13 and BU076U16)

The oxidation of triphenylphosphine in the presence of various photocatalytic systems (dicyanoanthracene/biphenyl, N-methylquinolinium, triphenylpyrylium, and thiatriphenylpyrylium tetrafluoroborate) was investigated by means of both steady state and laser flash photolysis experiments. The effect of different additives (including 1,4- benzoquinone, diphenylsulfoxide, tetramethylethylene, and sodium azide) on the photosensitized oxidation was investigated in order to fully characterize the involved intermediates. Photoinduced electron transfer and final regeneration of the catalyst occur when dicyanoanthracene and N-methylquinolinium are used, while in cage oxygen transfer to the photoexcited (thio)pyrylium derivatives have been characterized in the last two cases. Fil: Bonesi, Sergio Mauricio. PhotoGreen Lab; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina Fil: Protti, Stefano. PhotoGreen Lab; Italia Fil: Albini, Angelo. PhotoGreen Lab; Italia

Wet unsupported and supported 1,1′-binaphthalene-2,2′-diamine (BINAM) derived prolinamides are efficient organocatalysts under solvent-free conditions at room temperature to perform the synthesis of chiral tacrine analogues in good yields (up to 93%) and excellent enantioselectivies (up to 96%). The Friedländer reaction involved in this process takes place with several cyclohexanone derivatives and 2-aminoaromatic aldehydes, and it is compatible with the presence of either electron-withdrawing or electron-donating groups at the aromatic ring of the 2-aminoaryl aldehyde derivatives used as electrophiles. The reaction can be extended to cyclopentanone derivatives, affording a regioisomeric but separable mixture of products. The use of the wet silica gel supported organocatalyst, under solvent-free conditions, for this process led to the expected product (up to 87% enantiomeric excess), with its reuse being possible at least up to five times. This work was financially supported by the Ministerio de Ciencia e Innovación (MICINN: Projects: CTQ2010-20387 and Consolider Ingenio 2010 CSD2007-00006), the Generalitat Valenciana (Prometeo/2009/039, the University of Alicante and the EU (ORCA action CM0905). A.B.-C. thanks the Spanish MICINN for a predoctoral fellowship (FPU AP2009-3601).

The use of thiogalactofuranoside as donors for the construction of internal Galf containing oligosaccharide is limited, probably due to the difficulty to functionalize thiogalactofuranoside derivatives showing O-2, O-3, and O-5 with similar reactivity. An efficient method for complete regioselective 5-O-opening of conformationally restricted 3,5-O-di-tertbutylsilylene-D-galactofuranoside derivatives was developed. The use of a solution nBu4NF (1.1 equiv) in CH2Cl2 on 6 gave the 5-OH free derivative 10 as the only product (90%). 3-O-Di-tert-butylhydroxysilyl derivative 10 was stable upon purification and glycosylation reaction. Preactivation of conformationally restricted thioglycoside 6 employing p-NO2-benzensulfenyl chloride/AgOTf followed by condensation over the 5-OH thioglycoside acceptor 10 gave the corresponding disaccharide 12 without autocondensation byproduct. Regioselective 5-O-deprotection was also successfully performed over the (1→5)-β-D-galactofuranosyl di- and trisaccharide derivatives 12 and 13. This methodology allowed the differentiation between the secondary hydroxyl groups OH-3 and OH-5 of 1,2-cis or 1,2-trans D-galactofuranoside derivatives, and it still constitutes an innovative approach to access oligosaccharides of pharmacological importance. Fil: Tilve, Mariano Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina Fil: Cori Calizaya, Carmen Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina Fil: Gallo, Carola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina

A novel imide compound (C 16H 10ClNO 4) was synthesized in a single step by the reaction of 2-furoic acid with 4-chloroaniline in a 2:1 molar ratio using carbonyldiimidazole (CDI) in dry THF. The structure was supported by spectroscopic and elemental analyses and the single-crystal X-ray diffraction data. Crystallographic studies revealed that the compound crystallized in a monoclinic system with space group P2 1/c and unit cell dimensions a = 12.2575(5) Å, b = 7.7596(2) Å, c = 15.0234(7) Å, α = γ = 90°, β = 92.771(4)°, V = 1427.25(10) Å 3, Z = 4. The imide bond is twisted, and the O=C-N-C(O) units deviate significantly from planarity with dihedral angles around the imide group reaching ca. -150.3° (C1-N1-C2-O21 = -148.8° and C2-N1-C1-O11 = -151.9°). The nonplanarity of the imide moiety and the related conformational properties are discussed in a combined approach that includes the analysis of the vibrational spectra together with theoretical calculation methods, especially in terms of natural bond orbital (NBO) calculations. Fil: Saeed, Aamer. Quaid-I-Azam University; Pakistán Fil: Erben, Mauricio Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Bolte, Michael. Goethe Universitat Frankfurt; Alemania

A two-step synthesis of six-, seven-, eight-, and nine-member benzo-fused heterocycles in good to excellent yields is reported. The synthetic strategy involves the generation of a new intramolecular alpha-aryl ketone bond by the photostimulated SRN1 reaction of ketone enolate anions linked to a pendant haloarene as the key step. On the other hand, an intramolecular CAr-CAr coupling led to the formation of five- and six-member benzo-fused heterocycles (9H-carbazole and phenanthridine) when an aromatic amide anion is competitively formed Fil: Guastavino, Javier Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Investigaciones en Físicoquímica de Córdoba; Argentina. Universidad Nacional de Córdoba; Argentina Fil: Rossi, Roberto Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Investigaciones en Físicoquímica de Córdoba; Argentina. Universidad Nacional de Córdoba; Argentina

The synthesis of multivalent glycoclusters, designed to be compatible with biological systems, is reported. A variety of 1-thio-β-d-galactosides linked to a terminal triple bond through oligoethyleneglycol chains of variable lengths has been synthesized. Also, azide-containing oligosaccharide scaffolds were prepared from trehalose, maltose, and maltotriose by direct azidation with NaN3/PPh3/CBr4. Click reaction between the thiogalactoside residues and the azide scaffolds under microwave irradiation afforded a family of glycoclusters containing 1 to 4 residues of 1-thio-β-D-galactose. The yields went from moderate to excellent, depending on the valency of the desired product. Deacetylation with Et 3N/MeOH/H2O led to the final products. Complete characterization of the products was performed by NMR spectroscopy and HR-MS techniques. Their activities as inhibitors of β-galactosidase from E. coli were determined by using the Lineweaver-Burk method. The use of hydrophilic carbohydrate scaffolds for the synthesis of multivalent galactosides represents an interesting approach to improve their pharmacokinetics and bioavailability. In addition, the presence of the thioglycosidic bond will improve their stability in biological fluids. Fil: Cagnoni, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina Fil: Varela, Oscar Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina Fil: Gouin, Sébastien G.. Université de Picardie Jules Verne; Francia Fil: Kovensky, José. Université de Picardie Jules Verne; Francia Fil: Uhrig, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina

Six novel monoterpene chromane esters were isolated from the aerial parts of Peperomia obtusifolia (Piperaceae) using chiral chromatography. This is the first time that chiral chromane esters of this kind, ones with a tethered chiral terpene, have been isolated in nature. Due to their structural features, it is not currently possible to assess directly their absolute stereochemistry using any of the standard classical approaches, such as X-ray crystallography, NMR, optical rotation, or electronic circular dichroism (ECD). Herein we report the absolute configuration of these molecules, involving four chiral centers, using vibrational circular dichroism (VCD) and density functional theory (DFT) (B3LYP/6-31G*) calculations. This work further reinforces the capability of VCD to determine unambiguously the absolute configuration of structurally complex molecules in solution, without crystallization or derivatization, and demonstrates the sensitivity of VCD to specify the absolute configuration for just one among a number of chiral centers. We also demonstrate the sufficiency of using the so-called inexpensive basis set 6-31G* compared to the triple-ζ basis set TZVP for absolute configuration analysis of larger molecules using VCD. Overall, this work extends our knowledge of secondary metabolites in plants and provides a straightforward way to determine the absolute configuration of complex natural products involving a chiral parent moiety combined with a chiral terpene adduct.

Tetrahydrofuran derivatives can be obtained by cyclofunctionalization of homoallylic alcohols bearing a terminal double bound by using [hydroxy(tosyloxy)iodo]benzene (HTIB, Koser's reagent) in the presence of a catalytic amount of I(2) (20 mol %) in MeOH under mild conditions. This transformation is an overall 5-endo-trig cyclization, which occurs by two different pathways. The first is a 4-exo-trig cyclization followed by ring expansion, whereas the second is an electrophilic addition followed by a 5-endo-tet cyclization.

The existence and stability of the aldehyde-hydrate form of imidazole-2-carboxaldehyde (4) were studied using FTIR together with solution- and solid-state NMR experiments. The results allowed us to conclude that the hydrate form was stable and precipitated at pH = 8.0 and that the aldehyde form was isolated at pH = 6.5 and 9.5. Moreover, the presence of the aldehyde-hydrate form was studied through NMR experiments in D2O at both alkaline and acidic pH. In addition, the tautomeric forms of the 2-substituted imidazole compounds were also analyzed to investigate the influence of the hybridization on the carbon adjacent to the imidazole ring, by 13C NMR in DMSO-d6, acetone-d6, and CDCl3. The presence of the syn- and anti-isomers of oxime 8 obtained from 4 were characterized by solid-state NMR and variable-temperature NMR experiments in acetone-d 6. Fil: Lazaro Martinez, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Romasanta, Pablo Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: Chattah, Ana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina Fil: Buldain, Graciela Yolanda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

The oxidation of aryl methyl sulfides containing electron withdrawing and electron donating groups (p-NO2, p-CHO, p-NCS, p-Br, H, p-CH3, p-OCH3) was carried out in homogeneous solution in acetonitrile in the presence of catalytic amounts of HNO3 and FeBr3. The FeBr3 is required for the reaction to proceed for compounds with strongly electron withdrawing groups (p-NO2 and p-CHO) but is not necessary in the case of all the other compounds, although in the latter cases the yield decreases considerably. The rate of the reaction was measured as a function of substrate, FeBr3 and HNO3 concentration. From the experimental data a mechanism is suggested where there are two reaction pathways, one involving the formation of a ternary complex between the substrate, FeBr3 and NO 3- and one involving a complex formed between the sulfide and the HNO3. From these complexes HNO2 is generated, which then combines with HNO3 to yield N2O4, initiating a catalytic cycle where the sulfide is oxidized and O2 from the air is stoichiometrically consumed. Fil: Kinen, Claudio Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Rossi, Laura Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Hoyos, Maria Rita Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina

The physical-chemical properties of several 1,3-dithiafulvene (DTF) derivatives having a donor and acceptor group in the molecule were studied. The synthesis of these compounds produces selectively the E isomer, but when the compound is dissolved in CHCl3 isomerization to the Z isomer takes place with a rate that depends on the substituents. The interconversion rate is slow on the NMR time scale; therefore, two separated signals are observed, and they are used to measure the rate constant of isomerization. The equilibrium constant is, in all cases, very close to 1, and this is coincident with the fact that theoretical calculations of the energy of the two isomers in the gas phase differ by less than 0.1 kcal/mol. The isomerization reaction is completely reversible, and the E isomer can be obtained in pure form by selective crystallization. The derivatives with fhioalkyl groups have a strong tendency to aggregate in CDCl3. The formation of the aggregates is evidenced from the changes in ID 1H NMR and DOSY spectra as a function of concentration. The compounds are highly delocalized, and this is reflected by the low activation energy for the isomerization Fil: Fracaroli, Alejandro Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Granados, Alejandro Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Hoyos, Maria Rita Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina

Recoverable (Sa)-binam-l-prolinamide in combination with benzoic acid is used as catalysts in the direct aldol reaction between cycloalkyl, alkyl, and α-functionalized ketones and aldehydes under solvent-free reaction conditions. Three different methods are assayed: simple conventional magnetic stirring, magnetic stirring after previous dissolution in THF and evaporation, and ball mill technique. These procedures allow one to reduce not only the amount of required ketone to 2 equiv but also the reaction time to give the aldol products with regio-, diastereo-, and enantioselectivities comparable to those in organic or aqueous solvents. Generally anti-isomers are mainly obtained with enantioselectivities up to 97%. The reaction can be carried out under these conditions also using aldehydes as nucleophiles, yielding after in situ reduction of the aldol products the corresponding chiral 1,3-diols with moderate to high enantioselectivities mainly as anti-isomers. The aldol reaction has been studied by the use of positive ESI-MS technique, providing the evidence of the formation of the corresponding enamine−iminium intermediates. This work was financially supported by the Dirección General de Investigación of the Ministerio de Educación y Ciencia of Spain (Grant CTQ2004-00808/BQU, CTQ2007-62771/BQU and Consolider Ingenio 2010 CSD2007-00006), the Generalitat Valenciana (Grants CTIOIB/2002/320, GRUPOS03/134, and GV05/157), and the University of Alicante (GRJ06-05).

The preparation of N-methylpyrazoles is usually accomplished through reaction of a suitable 1,3-diketone with methylhydrazine in ethanol as the solvent. This strategy, however, leads to the formation of regioisomeric mixtures of N-methylpyrazoles, which sometimes are difficult to separate. We have determined that the use of fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvents dramatically increases the regioselectivity in the pyrazole formation, and we have used this modification in a straightforward synthesis of fluorinated analogs of Tebufenpyrad with acaricide activity. Fil: Fustero, Santos. Universidad de Valencia; España Fil: Roman, Raquel. Universidad de Valencia; España Fil: Sanz Cervera, Juan F.. Universidad de Valencia; España. Centro de Investigaciones Principe Felipe; España Fil: Simon Fuentes, Antonio. Universidad de Valencia; España Fil: Cuñat, Ana. Universidad de Valencia; España Fil: Villanova, Salvador. Universidad de Valencia; España Fil: Murguia, Marcelo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Two efficient protocols are described for the transformation of a key chiral homoallyllic sulfinamine intermediate in four steps into enantioenriched 7-methoxycryptopleurine. While one of the protocols relied on a rhodium catalyzed linear hydroformylation process, the alternative approach was based on a ring-closing metathesis from the corresponding N-allyl-sulfinamine. The cytotoxic evaluation of both enantiomers of the target compound demonstrated that the (R)-compound is much more potent than its antipode against the four cancer cell lines examined. We thank the Spanish Ministerio de Ciencia e Innovación (CTQ2011-24165) for financial support. I.B. acknowledges the Generalitat Valenciana for a postdoctoral fellowship (ACIF/2011/159). C.A.-T. thanks the ISO for a grant.

Conformationally restrained substituted pregnane-20-one derivatives were obtained by an intramolecular nitrene addition onto a C-5/C-6 double bond involving a tethered C-19 sulfamoyl moiety. The resulting aziridine underwent regioselective nucleophilic ring opening at C-5 at room temperature with cyanide, fluoride, and acetate. In the isolated case of acetate, a reversal of regioselectivity was observed at higher temperatures, a result attributed to a rearrangement process involving aziridine ring opening at the C-5 position and subsequent migration of the acetyl meiety to C-6. Fil: Duran, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina Fil: Ghini, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina Fil: Dauban, Philippe. Centre National de la Recherche Scientifique; Francia Fil: Dodd, Robert H.. Centre National de la Recherche Scientifique; Francia Fil: Burton, Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina

A study on the addition of trineophyltin hydride (1) to alkynones under free radical (AIBN and Et3B) and palladium-catalyzed [(PPh3) 2PdCl2] conditions is reported. The results obtained indicate that the addition of 1 to eight ynones catalyzed by bis(triphenylphosphine)palladium(II) chloride led in all cases to addition products in very high yields (80-96%). These additions take place with excellent regio- and stereochemistry, leading to the α adducts as major products in seven out of the eight cases studied. Also the E adducts, resulting from a syn attack, were the only (seven cases) or the predominant (one case) products. The radical hydrostannations initiated by AIBN of ynones 2-5 with 1 led to addition products in good yields (60-88%); with the more hindered ketones 6 and 7-9 the yields obtained were lower. The radical additions initiated by triethylboron to ynones 2-6 follow a similar pattern but with lower yields; no addition products in the hydrostannation of ynones 7-9 were detected. The new acyl-substituted vinylstannanes, owing to their greater stability compared with that of their tributyl- and trimethylstannyl analogues, can be purified by column chromatography using neutral alumina (in all cases) or silica gel 60 (in most cases) as adsorbents. Full 1H, 13C, and 119Sn NMR data are given. Fil: Dodero, Veronica Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Koll, Liliana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Faraoni, María Belén. Universidad Nacional del Sur. Departamento de Química; Argentina Fil: Mitchell, Terence N.. Universität Dortmund; Alemania Fil: Podestá, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina

Producción Científica, Enantioenriched trisubstituted lactones were obtained in good yields and moderate to very good enantioselectivities in one-pot process, which implies a sequential organocatalyzed Michael addition of ketones to enals, followed by catalytic intramolecular diastereoselective Tishchenko reaction and lactonization. The final lactones were obtained as single diastereoisomers, demonstrating that the mixture of the anti and syn diastereomers epimerized to the syn hydroxy ester during the oxido-reduction step., Ministerio de Economía, Industria y Competitividad (CTQ 2011-28487), Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA064U13), Universidad de Valladolid for a pre-doctoral fellowships