Coupled domino processes: Synthesis of 3,5,8-trisubstituted coumarins from propargyl vinyl ethers

The generation of a small and representative library of 3,5,8-trisubstituted coumarins (21 compounds, 7 families, 3 groups) is described. The library was built from the corresponding propargyl vinyl ethers and three different 1,3-dicarbonyl derivatives using a one-pot coupled domino strategy. These coumarins constitute a novel chemotype defined by the presence of a chemical handle in the pyranone ring and a varied substitution pattern adorning the aromatic ring, which includes fluorine- or oxygen-containing functionalities. © 2013 American Chemical Society.This research was supported by the Spanish Ministerio de Economía y Competitividad (MICINN) and the European Regional Development Fund (CTQ2011- 28417-C02-02). L.C. thanks the Spanish MEC for an FPI grant.Peer Reviewe

A convenient domino access to substituted alkyl 1,2-dihydropyridine- 3carboxylates from propargyl enol ethers and primary amines

A convenient domino access to substituted alkyl 1,2-dihydropyridine-3- carboxylates from propargyl enol ethers and primary amines was reported. A solution of propargyl sinyl ether 1a and p-anisidine in toluene was placed in a microwave-special closed vial and the solution was irradiated for 30 minutes in a single-mode microwave oven. The reaction mixture was dried over anhydrous sodium sulfate and filtrated using dichloromethane as solvent. After removing the solvent at reduced pressure the products were purified by flash column chromatography. Accordingly, the microwave irradiation of an ethanolic mixture of propargyl enol ether 1 a and MeONH2.HCl in the presence of NaOAc yielded the methyl 2-phenyl-4-pyridinecarboxylate in a convenient 54% yield. These results seem to point out to a new reaction pathway involving different thermally-driven rearrangements of the 2,4-dienal 3 intermediate.This research was supported by the Spanish Ministerio de Ciencia e Innovación, the European Regional Development Fund (CTQ2005-09074-C02-02 and CTQ2008-06806-C02-02) and the Spanish MSC ISCIII (RETICS, RD06/0020/1046, and RD06/0020/0041), CSIC (Proyecto Intramural Especial 200719), FUNCIS (REDESFAC PI01/06 and 35/06) and the Fundación Instituto Canario de Investigación del Cancer (FICI-G.I.N808/2007). G.M.-A. thanks Spanish MEC for a FPU grant.Peer Reviewe

Web de apoyo a una aplicación Android de fisioterapia

Las aplicaciones de apoyo a la salud se están convirtiendo en herramientas necesarias en el día a día, tanto las destinadas a los profesionales sanitarios como las dirigidas solamente a los pacientes. Sin embargo, no todas las áreas de la medicina están suficientemente apoyadas por este tipo de aplicaciones. En concreto, la fisioterapia es uno de las áreas de la salud que necesita un mayor esfuerzo en este sentido. En este Trabajo Fin de Grado se propone el desarrollo de una Web que sirva de apoyo a la aplicación Android que ha sido desarrollada en conjunto con Jairo Méndez y Javier Mallo, gracias a ella se podrán realizar tareas de forma sencilla que con la aplicación resultarían complicadas y poco útiles. Con la versión Web se podrán realizar las mismas tareas que se realizaban con la aplicación Android (obtener información sobre las clínicas asociadas a la aplicación, realizar reservas, interactuar con su fisioterapeuta asignado pudiendo contactar con él y recibir consejos y ejercicios adecuados para su problema), a mayores de estas funcionalidades se podrán realizar otras, como bloquear unas determinadas horas de la clínica, para que no se puedan realizar reservas durante ese periodo, administrar y gestionar todos los productos y servicios ofrecidos (modificar, añadir o borrar los tratamientos o ejercicios), que la aplicación móvil no poseía, y que son necesarias para el efectivo funcionamiento del servicio.Grado en Ingeniería de Tecnologías Específicas de Telecomunicació

General synthesis of substituted 1,2-dihydropyridines

A general and practical metal-free protocol for the synthesis of 1,2-dihydropyridines with wide structural/functional diversity at the ring and featuring mono, double, or spiro substitution at the sp3 position is described. The protocol entails a microwave-assisted domino reaction of a propargyl vinyl ether (secondary or tertiary) and a primary amine (aliphatic or aromatic) in toluene or methanol. © 2014 American Chemical Society.This research was supported by the Spanish Ministerio de Economı́a y Competitividad (MICINN) and the European Regional Development Fund (CTQ2011-28417-C02-02). L.C. and G.M.-A. thank the Spanish MEC for FPI and FPU grants, respectively.Peer Reviewe

Merging domino and redox chemistry: Stereoselective access to di- and trisubstituted β,γ-unsaturated acids and esters

Merging is the game! The coupling of a domino reaction and an internal neutral redox reaction constitutes an excellent manifold for the stereoselective synthesis of di- and trisubstituted olefins featuring a malonate unit, an ester, or a free carboxylic acid as substituents at the allylic position (see scheme; MW=microwave). The reaction utilizes simple starting materials (propargyl vinyl ethers), methanol or water as solvents, and a very simple and bench-friendly protocol. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.This research was supported by the Spanish MICINN and the European RDF (CTQ2008–06806-C02–02), the Spanish MSC ISCIII (RETICS RD06/0020/1046), FUNCIS (REDESFAC PI01/06). G. M.-A. and L. C. thank Spanish MEC for FPU and FPI grants, respectively.Peer Reviewe

Propargyl Claisen rearrangement: Allene synthesis and beyond

The propargyl Claisen rearrangement is a known protocol to gain access to functionalized allenes through the [3,3]-sigmatropic transformation of propargyl vinyl ethers. The correct use of appropriate propargyl vinyl ethers as starting materials coupled with suitable reaction conditions can aid in the development of new domino methodologies in which the allenes are valuable intermediates in route to a wide range of important classes of organic compounds. © The Royal Society of Chemistry 2013.This research was supported by the Spanish Ministerio de Economía y Competitividad and the European Regional Development Fund (CTQ2011-28417-C02-02). G.M.A. and L.C. thank the Spanish MEC for FPU and FPI grants, respectively.Peer Reviewe

The free-linking task: a graph-inspired method for generating non-disjoint similarity data with food products

"Free sorting", in which subjects are asked to sort a set of items into groups of "most similar" items, is increasingly popular as a technique for profiling sets of foods. However, free sorting implies an unrealistic model of sample similarity: that similarity is purely binary (is/is not similar) and that similarity is fully transitive (similarities {A, B} and {B, C} imply {A, C}). This paper proposes a new method of rapid similarity testing -- the "free-linking" task -- that solves both problems: in free linking, subjects draw a similarity graph in which they connect pairs of samples with a line if they are similar, according to the subject s individual criteria. This simple task provides a more realistic model of similarity which allows degrees of similarity through the graph distance metric and does not require transitive similarity. In two pilot studies with spice blends (10 samples, 58 subjects) and chocolate bars (10 samples, 63 subjects), free linking and free sorting are evaluated and compared using DISTATIS, RVb, and the graph parameters degree, transitivity, and connectivity; subjects also indicated their preferences and ease-of-use for the tasks. In both studies, the first two dimensions of the DISTATIS consensus were highly comparable across tasks; however, free linking provided more discrimination in dimensions three and four. RVb stability was equivalent for the two methods. Graph statistics indicated that free linking had greater discrimination power: on average subjects made similarity groupings with lower degree, lower transitivity, and higher connectivity for free linking in both studies. However, subjects did overall find free sorting easier and liked it more, indicating a higher cognitive difficulty of free linking. The free-linking task, therefore, provides more robust, realistic similarity maps at the cost of higher panelist effort, and should prove a valuable alternative for rapid sensory assessment of product sets.Agencia Estatal de Investigació

Tertiary skipped diynes: A pluripotent building block for the modular and diversity-oriented synthesis of nitrogen heterocycles

Dominos! The multivalent reactivity profile of tertiary skipped diynes has been conveniently exploited in the domino and diversity-oriented synthesis of fully substituted pyrazoles and 1, 4-diazepane derivatives (see scheme). The developed manifold is chemically efficient and simple to operate. In addition, the resulting Ncontaining heterocycles are obtained in a regio- and chemoselective manner. (Chemical Equation Presented) © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.This research was supported by the Spanish Ministerio de Ciencia e Innovación, the European Regional Development Fund (CTQ2008-06806-C02-02), the Spanish MSC ISCIII (RETICS RD06/0020/1046), FUNCIS (REDESFAC PI01/06) and the Fundación Instituto Canario de Investigación del Cancer (FICI-G.I.N808/2007). S.L.-T. thanks the Spanish MEC for an FPU grant. The authors thank technician Anna Jurado Varona for her experimental assistance.Peer Reviewe

Diverted domino reactivity in tertiary skipped diynes: A convenient access to polyfunctionalized cyclohexadienones and multivalent aromatic scaffolds

Diverting is the game! A new domino manifold has been implemented for the synthesis of cyclohexadienone-based scaffolds from tertiary skipped diynes and secondary amines. The manifold takes advantage of a new O-enolate-driven reactivity pattern discovered for these diynes. The scaffolds are conveniently transformed into the corresponding multivalent salicylate derivatives (see scheme). © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.This research was supported by the Spanish MICINN and the European RDF (CTQ2008–06806-C02–02), the Spanish MSC ISCIII (RETICS RD06/0020/1046), FUNCIS (PI 43/09). S. L.-T. thanks the Spanish MEC for a FPU grant. The authors thank technician Ms. Anna Jurado Varona for her experimental assistance.Peer Reviewe

From conjugated tertiary skipped diynes to chain-functionalized tetrasubstituted pyrroles

A novel and metal-free method for the synthesis of chain-functionalized tetrasubstituted pyrroles from easily accessible tertiary skipped diynes, was reported. The method involved modular synthesis of chain functionalized tetrasubstituted pyrroles from easily available alkyl porpiolates, acid chlorides, and primary amine. The method used a primary amine for the nitrogen source and utilized the reactivity profile of tertiary 1,4-diyne scaffolds. The synthetic manifold in the method operated in the absence of metals and accelerated by the nucleophilic addition of a primary amine on the alkynoate function. Anti-Michael ring-closing hydroamination and a [3,3]-sigmatropic rearrangement helped to complete the process of producing pyrrole. It was observed during the process that the enamine formation is more faster than the enamine cyclization.Authors thank the Spanish Ministerio de Educación y Ciencia and the European Regional Development Fund (CTQ2005-09074-C02-02), the Spanish MSC ISCIII (RETICS RD06/0020/1046), CSIC (Proyecto Intramural Especial 200719) and Fundación Instituto Canario de Investigación del Cáncer (FICI-G.I. No. 08/2007) for financial support. S.L.-T. Thanks MEC for a FPU grant.Peer Reviewe