RAF agradece a la Fundación Nacional de Ciencia (CHE-0844946) para el apoyo de este trabajo.

1. Síntesis de SmI 2 (0,1 M) <ol><li> Llama seco de 50 ml, matraz de fondo redondo y lávelo con argón. Añadir una barra de agitación y cubrir el recipiente con septos. Pesar samario metálico (0,2 g, 1,3 mmol) y se añade al matraz, de nuevo lavado del matraz con argón. </li><li> Añadir 10 ml seco, completamente desgasificada de tetrahidrofurano (THF), seguido de cristales de yodo (0,254 g, 2,0 mmol). Añadir un balón de argón a través del tabique, lo que mantiene una presión positiva de la atmósfera de Ar sobre la reacción. </li><li> Agitar la solución vigorosamente a temperatura ambiente durante más de 3 horas. Como SmI 2 se genera la solución pasa a través de una variedad de cambios de color naranja seguido por el amarillo (45 min), y verde (1 h) que eventualmente se convierte en azul. </li><li> La final de color azul marino es indicación de que simplemente ionizado samario se ha formado. Con el fin de asegurar la conversión completa, se agita la solución durante al menos 3 horas antes de utilizar SmI 2 en la síntesis. </li></ol> 2. Samarium Barbier-Reacción hexametilfosforamida (HMPA) Adición <ol><li> Para hacer que el SMI 2-HMPA complejo, tomar la recién preparada SmI 2 en atmósfera de argón (10 ml, 0,1 M, 1,0 mmol) y se añade 1,75 ml de HMPA (10 equiv., 10 mmol) mediante una jeringa, gota a gota, en atmósfera de argón. Se forma un color morado oscuro en color. </li><li> Por separado en un vial limpio y seco, en atmósfera de argón, se añade iodododecane (0,45 mmol, 110 l), 3-pentanona (0,45 mmol, 48 l) y 2 ml de THF seco. </li><li> Añadir la mezcla gota a gota solución de sustrato para el SMI 2 / HMPA complejo. </li><li> Dentro de 5 minutos de agitación, el color púrpura empezará a tener un aspecto turbio, lo que indica el final de la reacción. </li><li> Después de que la reacción es completa, exponer la solución a aire para extinguirlo; después de agitar los cambios de color adicionales a amarillo. </li><li> La reacción se elaboró ​​por lavado con cloruro de amonio acuoso saturado. Añadir la solución a un embudo de separación y añadir éter dietílico (5 ml). Después de una agitación vigorosa eliminarla capa orgánica superior, añadir más éter dietílico. Extracto de la capa acuosa dos veces más y entonces combinar todas las capas orgánicas. </li><li> Se lava la capa orgánica con una solución saturada de tiosulfato de sodio acuoso. Eliminar la capa acuosa inferior, seguido de lavado con agua y después lavado final con salmuera. Obtener la capa orgánica superior y añadir sulfato de magnesio para que absorba la última cantidad de agua presente en la solución. </li><li> Pasar la solución a través de un tapón de Florisil con el fin de eliminar el exceso de HMPA. </li><li> Se concentra la solución en un evaporador rotatorio para obtener Barbier producto. El producto se identificó por GCMS y RMN 1 H. 23 </li></ol> 3. Samario Barbier Reaction-Ni (acac) 2 Catalizador <ol><li> Pesar Ni (acac) 2 (1% en moles, 0,01 mmol, 0,0026 g) y se añade a un vial limpio y seco, que contiene 3 ml de THF desgasificado, en atmósfera de argón. Añadir el Ni (acac) 2 solución a través de una jeringa a una s recién preparadolución de 0,1 M SmI 2 (1,0 mmol, 10 ml). </li><li> Por separado en un vial limpio y seco, en atmósfera de argón, se añade iodododecane (0,45 mmol, 110 l), 3-pentanona (0,45 mmol, 48 l) y 2 ml de THF seco. </li><li> Añadir gota a gota la solución de sustrato para el SMI 2 / mezcla Ni. </li><li> A los quince minutos de agitación, el color azul se disipará para formar un color amarillo-verde que indica el final de la reacción. </li><li> Después de que la reacción es completa, exponer la solución a aire para extinguirlo; después de agitar los cambios de color adicionales a amarillo. Trabajo hasta la reacción por lavado con 0,1 M aq. El ácido clorhídrico (3 ml). Añadir la solución a un embudo de separación y añadir éter dietílico (5 ml). </li><li> Se lava la capa orgánica usando el protocolo descrito anteriormente con una solución acuosa de tiosulfato de sodio, agua y salmuera, y después se seca sobre sulfato de magnesio. Se concentra la solución para obtener Barbier producto. El producto puede ser identificado por GCMS y RMN 1 H. 28 </sup&gt; </li></ol>

<ol>
	<li>Girard, P., Namy, J. L., Kagan, K. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Divalent+lanthanide+derivatives+in+organic+synthesis.+1.+Mild+preparation+of+samarium+iodide+and+ytterbium+iodide+and+their+use+as+reducing+or+coupling+agents.">Divalent lanthanide derivatives in organic synthesis. 1. Mild preparation of samarium iodide and ytterbium iodide and their use as reducing or coupling agents.</a> J. Am. Chem. Soc. 102, 2693-2698 (1980).</li><li>Szostak, M., Spain, M., Procter, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preparation+of+samarium(II)+iodide:+quantitative+evaluation+of+the+effect+of+water,+oxygen,+and+peroxide+content,+preparative+methods,+and+activation+of+samarium+metal.">Preparation of samarium(II) iodide: quantitative evaluation of the effect of water, oxygen, and peroxide content, preparative methods, and activation of samarium metal.</a> J. Org. Chem. 77, 3049-3053 (2012).</li><li>Procter, D. J., Flowers, R. A., Skrydstrup, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Organic synthesis using samarium diiodide: a practical guide. , (2010).</li><li>Nicolaou, K. C., Ellery, S. P., Chen, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Samarium+diiodide+mediated+reactions+in+total+synthesis.">Samarium diiodide mediated reactions in total synthesis.</a> Angew. Chem. Int. Ed. 48, 7140-7165 (2009).</li><li>Flowers, R. A., Prasad, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Handbook on the physics and chemistry of rare earths. 36, 393-473 (2006).</li><li>Edmonds, D. J., Johnston, D., Procter, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Samarium(II)-iodide-mediated+cyclizations+in+natural+product+synthesis.">Samarium(II)-iodide-mediated cyclizations in natural product synthesis.</a> Chem. Rev. 104, 3371-3403 (2004).</li><li>Kagan, H. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Twenty-five+years+of+organic+chemistry+with+diiodosamarium:+an+overview.">Twenty-five years of organic chemistry with diiodosamarium: an overview.</a> Tetrahedron. 59, 10351-10372 (2003).</li><li>Steel, P. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+developments+in+lanthanide+mediated+synthesis.">Recent developments in lanthanide mediated synthesis.</a> J. Chem. Soc., Perkin Trans. 1, 2727-2884 (2001).</li><li>Molander, G. A., Harris, C. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sequencing+reactions+with+samarium(II)+iodide.">Sequencing reactions with samarium(II) iodide.</a> Chem. Rev. 96, 307-338 (1996).</li><li>Molander, G. A., Harris, C. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sequenced+reactions+with+samarium(II)+iodide.+Tandem+intramolecular+nucleophilic+acyl+substitution/intramolecular+Barbier+cyclizations.">Sequenced reactions with samarium(II) iodide. Tandem intramolecular nucleophilic acyl substitution/intramolecular Barbier cyclizations.</a> J. Am. Chem. Soc. 117, 3705-3716 (1995).</li><li>Molander, G. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Application+of+lanthanide+reagents+in+organic+synthesis.">Application of lanthanide reagents in organic synthesis.</a> Chem. Rev. 92, 29-68 (1992).</li><li>Souppe, J., Danon, L., Namy, J. L., Kagan, K. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Some+organic-reactions+promoted+by+samarium+diiodide.">Some organic-reactions promoted by samarium diiodide.</a> J. Organometal. Chem. 250, 227-236 (1983).</li><li>Flowers, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanistic+studies+on+the+roles+of+cosolvents+and+additives+in+samarium(II)-based+reductions.">Mechanistic studies on the roles of cosolvents and additives in samarium(II)-based reductions.</a> Synlett. 10, 1427-1439 (2008).</li><li>Hutton, T. K., Muir, K., Procter, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Samarium(II)-mediated+reactions+of+gamma,+delta-unsaturated+ketones.+Cyclization+and+fragmentation+processes.">Samarium(II)-mediated reactions of gamma, delta-unsaturated ketones. Cyclization and fragmentation processes.</a> Org. Lett. 4, 2345-2347 (2002).</li><li>Miller, R. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reactions+of+SmI2+with+alkyl+halides+and+ketones:+inner-sphere+vs+outer-sphere+electron+transfer+in+reactions+of+Sm(II)+reductions.">Reactions of SmI2 with alkyl halides and ketones: inner-sphere vs outer-sphere electron transfer in reactions of Sm(II) reductions.</a> J. Am. Chem. Soc. 122, 7718-7722 (2000).</li><li>Ito, Y., Takahashi, K., Nagase, H., Honda, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Integral+stereocontrolled+synthesis+of+a+spiro-norlignan,+sequosempervirin+A:+revision+of+absolute+configuration.">Integral stereocontrolled synthesis of a spiro-norlignan, sequosempervirin A: revision of absolute configuration.</a> Org. Lett. 13, 4640-4643 (2011).</li><li>Molander, G. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Toward+the+total+synthesis+of+Variecolin.">Toward the total synthesis of Variecolin.</a> Org. Lett. 3, 2257-2260 (2001).</li><li>Shabangi, M., Flowers, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrochemical+investigation+of+the+reducing+power+of+SmI2+in+THF+and+the+effect+of+HMPA+cosolvent.">Electrochemical investigation of the reducing power of SmI2 in THF and the effect of HMPA cosolvent.</a> Tetrahedron Lett. 38, 1137-1140 (1997).</li><li>Enenaerke, R. J., Hertz, T., Skrydstrup, T., Daasbjerg, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evidence+for+ionic+samarium(II)+species+in+THF/HMPA+solution+and+investigation+of+Their+electron-donating+properties.">Evidence for ionic samarium(II) species in THF/HMPA solution and investigation of Their electron-donating properties.</a> Chem. Eur. J. 6, 3747-3754 (2000).</li><li>Hou, Z., Zhang, Y., Wakatsuki, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+structures+of+HMPA-coordinated+samarium(II)+and+ytterbium(II)+iodide+complexes.+A+structural+basis+for+the+HMPA+effects+in+SmI2-promoted+reactions.">Molecular structures of HMPA-coordinated samarium(II) and ytterbium(II) iodide complexes. A structural basis for the HMPA effects in SmI2-promoted reactions.</a> Bull. Chem. Soc. Jpn. 70, 149-153 (1997).</li><li>Hou, Z., Wakatsuki, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=+Isolation+and+x-ray+structures+of+the+hexamethylphosphoramide+(hmpa)-coordinated+lanthanide(II)+diiodide+complexes+[SmI2(hmpa)4]+and+[Yb(hmpa)4(thf)2]I2."> Isolation and x-ray structures of the hexamethylphosphoramide (hmpa)-coordinated lanthanide(II) diiodide complexes [SmI2(hmpa)4] and [Yb(hmpa)4(thf)2]I2.</a> J. Chem. Soc., Chem Commun. 10, 1205-1206 (1994).</li><li>Sadasivam, D. V., Antharjanam, P. K. S., Prasad, E., Flowers, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanistic+study+of+samarium+diodide-HMPA+initiated+5-exo-trig+ketyl-Olefin+coupling:+the+role+of+HMPA+in+post-electron+transfer+steps.">Mechanistic study of samarium diodide-HMPA initiated 5-exo-trig ketyl-Olefin coupling: the role of HMPA in post-electron transfer steps.</a> J. Am. Chem. Soc. 130, 7228-7229 (2008).</li><li>Choquette, K. A., Sadasivam, D. V., Flowers, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Uncovering+the+mechanistic+role+of+HMPA+in+the+samarium+Barbier+reaction.">Uncovering the mechanistic role of HMPA in the samarium Barbier reaction.</a> J. Am. Chem. Soc. 132, 17396-17398 (2010).</li><li>Molander, G. A., Hu&#233;rou, V. L., Brown, G. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sequenced+reactions+with+samarium(II)+iodide.+Sequential+intramolecular+Barbier+byclization/Grob+fragmentation+for+the+synthesis+of+medium-sized+carbocycles.">Sequenced reactions with samarium(II) iodide. Sequential intramolecular Barbier byclization/Grob fragmentation for the synthesis of medium-sized carbocycles.</a> J. Org. Chem. 66, 4511-4516 (2001).</li><li>Molander, G. A., K&#246;llner, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+a+protocol+for+eight-+and+nine-membered+ring+synthesis+in+the+annulation+of+sp2,sp3-hybridized+organic+dihalides+with+keto+ester.">Development of a protocol for eight- and nine-membered ring synthesis in the annulation of sp2,sp3-hybridized organic dihalides with keto ester.</a> J. Org. Chem. 65, 8333-8339 (2000).</li><li>Molander, G. A., Alonso-Alija, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sequenced+reactions+with+samarium(II)+iodide.+Sequential+intermolecular+carbonyl+addition/intramolecular+nucleophilic+acyl+substitution+for+the+preparation+of+seven-,+eight-,+and+nine-membered+carbocycles.">Sequenced reactions with samarium(II) iodide. Sequential intermolecular carbonyl addition/intramolecular nucleophilic acyl substitution for the preparation of seven-, eight-, and nine-membered carbocycles.</a> J. Org. Chem. 63, 4366-4373 (1998).</li><li>Machrouhi, F., Hamann, B., Namy, J. L., Kagan, K. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+reactivity+of+diiodosamarium+by+catalysis+with+transition+metal+salts.">Improved reactivity of diiodosamarium by catalysis with transition metal salts.</a> Synlett. 7, 633-634 (1996).</li><li>Choquette, K. A., Sadasivam, D. V., Flowers, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Catalytic+Ni(II)+in+reactions+of+SmI2:+Sm(II)-+or+Ni(0)-+based+chemistry?.">Catalytic Ni(II) in reactions of SmI2: Sm(II)- or Ni(0)- based chemistry?.</a> J. Am. Chem. Soc. 133, 10655-10661 (2011).</li></ol>

No hay conflictos de interés declarado.

Un procedimiento sencillo para la generación de SMI 2 solución y su aplicación en síntesis orgánica utilizando dos de los aditivos más comunes que se presentan aquí. Los dos ejemplos descritos retratar la importancia de comprender el mecanismo de la reacción para ajustar la reactividad de SMI 2. El conocimiento de la apuntalamiento del mecanismo de reacción permite que el uso de este reactivo a ser adaptado por los químicos sintéticos como por las necesidades de su reacción. Este único reductor homogénea de electrones es fácil de manejar y se pueden adquirir de fuentes comerciales. Mientras que el protocolo anterior es directa cuando se realiza bajo condiciones inertes, algunos de los procedimientos de resolución de problemas comunes son: (a) asegurarse de que el THF se desgasificó y se seca adecuadamente, (b) si el metal Sm ha tenido una exposición prolongada al aire que podría tener un oxida la capa exterior, moler el metal con un mortero y pestal para exponer la superficie metálica limpia, (c)llama secar el material de vidrio y enfriar en atmósfera de argón, (d) de argón se prefiere atmósfera inerte en nitrógeno, como la tarde se ha demostrado que interactúan con el metal, (e) La presencia de exceso de Sm-metal ayuda a mantener la concentración de SmI 2, (f) resublime los cristales de yodo.

<table border="1"><tbody><tr><td> Nombre del reactivo </td><td> Empresa </td><td> Número de catálogo </td><td> Comentarios (opcional) </td></tr><tr><td> Samario metálico </td><td> Acros </td><td> 29478-0100 </td><td> Malla -40, 99,9% (base metales) </td></tr><tr><td> THF </td><td> OmniSolv </td><td> TX0282-1 </td><td> Purificada a través de sistema de purificación de Tecnologías Innovadoras solvente. Alternativamente, puede ser desgasificado mediante libre-bomba-descongelación </td></tr><tr><td> Yodo </td><td> Alfa Aesar </td><td> 41955-22 </td><td> Cristales resublimado, el 99,8% </td></tr><tr><td> Iodododecane </td><td> Acros </td><td> 25009-0250 </td><td> 98% </td></tr><tr><td> 3-pentanona </td><td> Alfa Aesar </td><td> AAA15297-AE </td><td> 99% </td></tr><tr><td> HMPA </td><td> Alderich </td><td> H11602 </td><td> 98%; Destilar de CaO en atmósfera de argón </td></tr><tr><td> Nii 2 </td><td> Alfa Aesar </td><td> 22893 </td><td> 99,5% (base de metales) </td></tr></tbody></table>

preparation and use of samarium diiodide (smi2) in organic synthesis: the mechanistic role of hmpa and ni(ii) salts in the samarium barbier reaction

Aunque al principio se considera un reactivo esotérico, SMI 2 se ha convertido en una herramienta común para los químicos orgánicos sintéticos. SmI 2 se genera a través de la adición de yodo molecular al samario metal en THF. 1,2-3 Se trata de un único electrón reductor suave y selectivo y su versatilidad es consecuencia de la capacidad de iniciar una amplia gama de reducciones incluyendo enlace CC- y formando cascada o reacciones secuenciales. SmI 2 puede reducir una variedad de grupos funcionales incluyendo sulfóxidos y sulfonas, óxidos de fosfina, epóxidos, haluros de alquilo y arilo, carbonilos, y dobles enlaces conjugados. 2-12 Una de las características interesantes de SMI-2-reacciones mediadas es la capacidad manipular el resultado de las reacciones mediante el uso selectivo de los codisolventes o aditivos. En la mayoría de casos, los aditivos son esenciales en el control de la tasa de reducción y las reacciones de quimio-o estereoselectividad de. 13-14 Aditivos commonly utilizado para ajustar la reactividad de SMI 2 pueden clasificarse en tres grupos principales: (1) bases de Lewis (HMPA, otros ligandos donadores de electrones, éteres quelantes, etc), (2) fuentes de protones (alcoholes, agua, etc ), y (3) los aditivos inorgánicos (Ni (acac) 2, FeCl 3, etc). 3 La comprensión del mecanismo de SMI 2 reacciones y el papel de los aditivos permite la utilización de todo el potencial del reactivo en síntesis orgánica. La reacción Sm-Barbier es elegido para ilustrar la importancia sintético y función mecánica de dos aditivos comunes: HMPA y Ni (II) en esta reacción. La reacción Sm-Barbier es similar a la tradicional reacción de Grignard con la única diferencia de que el alquilo haluro de carbonilo, y Sm reductor se mezclan simultáneamente en un solo recipiente. 1,15 ejemplos de reacciones mediadas por Barbier Sm con una variedad de asociados de acoplamiento se ha informado, 1,3,7,10,12 y han sido utilized en pasos clave de la síntesis de grandes productos naturales. 16,17 Estudios anteriores sobre el efecto de los aditivos en el SMI 2 reacciones han demostrado que HMPA aumenta el potencial de reducción de SmI 2 coordinando, en el centro de samario metal, produciendo una más potente, 13-14,18 estéricamente gravado reductor 19-21 y en algunos casos juegan un papel integral en puestos de transferencia de electrones que faciliten pasos subsiguientes forman el enlace de eventos. 22 En la reacción de Sm-Barbier, HMPA se ha demostrado que activar adicionalmente el haluro de alquilo mediante la formación de un complejo en una etapa de pre-equilibrio. 23 Ni (II) son las sales de un aditivo catalítico utilizado frecuentemente en Sm mediadas transformaciones. Aunque crítico para el éxito 24-27, la función mecánica de Ni (II) no era conocido en estas reacciones. Recientemente se ha demostrado que reduce SmI 2 Ni (II) a Ni (0), y la reacción se lleva a cabo a través de organometallic Ni (0) química 28. Estos estudios mecanísticos destacar que aunque el producto Barbier se obtiene la misma, el uso de aditivos diferentes en el SMI 2 reacción altera drásticamente el mecanismo de la ruta de la reacción. El protocolo para el funcionamiento de estos SmI 2-iniciados reacciones se describe.

La Figura 1 ilustra la reacción de Barbier samario. Sin aditivos de la reacción Sm mediada toma 72 hr; dando 69% del producto deseado con los restantes son materiales de partida. Con la adición de 10 o más equiv. de HMPA la reacción es casi cuantitativa y completa en unos pocos minutos. 15,23 Con la adición de 1 mol% de Ni (acac) 2, la reacción se completa en 15 min, con un rendimiento de 97%. 28 Cuando se añade HMPA a SMI 2, los desplaza cosolventes El THF coordinado para formar SmI 2 - (HMPA) 4. Con la adición de incluso más HMPA (6-10 equiv.), Los iones de yoduro son desplazados a la esfera exterior (Figura 2). 19-21 Estudios mecanísticos indican que cuando HMPA se utiliza en la reacción de Sm-Barbier el codisolvente también interactúa con el haluro de alquilo sustrato formando un complejo que alarga el enlace carbono-haluro, la activación de la species haciéndola más susceptible a la reducción por Sm (Figura 3). A través de esta comprensión detallada de las funciones de HMPA, un mecanismo para la reacción de Barbier con Sm-HMPA fue propuesto (Figura 4). 23 El haluro de alquilo-HMPA complejo formado en una etapa de pre-equilibrio se reduce por Sm / HMPA para formar el radical en el paso determinante de la velocidad. El radical se somete a reducción adicional para formar una especie organosamarium que se acopla con el carbonilo y sobre los rendimientos de la protonación del producto final. En el caso de Ni (II) aditivo, SmI 2 reduce inicialmente Ni (II) a Ni (0) preferentemente con respecto a la reducción de cualquiera de los sustratos. Basado en los estudios cinéticos y mecanísticos el mecanismo se propuso el siguiente (Figura 5). 28 después de la reducción por SMI 2, el NI soluble (0) insertos especies en el enlace haluro de alquilo formando una especie organonickel. Impulsada por la naturaleza altamente oxófilo de Sm (III)<html> , Transmetalación para formar un intermedio organosamarium comunicados de Ni (II) de nuevo en el ciclo catalítico. El organosamarium entonces pareja con el carbonilo, y sobre la protonación forma el alcohol terciaria deseada. También se observó que el Ni (0) nanopartículas se forman a través de Sm-mediada por la reducción de Ni (II), sin embargo estas partículas resultaron ser inactivo y la fuente de la desactivación del catalizador. <img alt="Figura 1" fo:content-width="4in" fo:src="/files/ftp_upload/4323/4323fig1highres.jpg" src="/files/ftp_upload/4323/4323fig1.jpg" /> Figura 1. Samario Barbier reacción con iodododecane y 3-pentanona. <img alt="Figura 2" fo:content-width="4in" fo:src="/files/ftp_upload/4323/4323fig2highres.jpg" src="/files/ftp_upload/4323/4323fig2.jpg" /> Figura 2. SmI 2-HMPA complejo. ontenido &quot;fo: keep-together.within-page =&quot; always &quot;&gt; <img alt="Figura 3" fo:content-width="3.5in" fo:src="/files/ftp_upload/4323/4323fig3highres.jpg" src="/files/ftp_upload/4323/4323fig3.jpg" /> Figura 3. HMPA y complejo yoduro de alquilo. <img alt="Figura 4" fo:content-width="4.5in" fo:src="/files/ftp_upload/4323/4323fig4highres.jpg" src="/files/ftp_upload/4323/4323fig4.jpg" /> Figura 4. Mecanismo propuesto para la reacción de Barbier samario con HMPA exceso. <img alt="Figura 5" fo:content-width="4in" fo:src="/files/ftp_upload/4323/4323fig5highres.jpg" src="/files/ftp_upload/4323/4323fig5.jpg" /> Figura 5. Mecanismo propuesto para la reacción samario Barbier catalítico que contiene Ni (II).

Watch this Scientific Journal Video about Preparation and Use of Samarium Diiodide SmI2 in Organic Synthesis: The Mechanistic Role of HMPA and NiII Salts in the Samarium Barbier Reaction at JoVE.com

Preparation and Use of Samarium Diiodide SmI2 in Organic Synthesis: The Mechanistic Role of HMPA and NiII Salts in the Samarium Barbier Reaction

Un procedimiento sencillo para la preparación de samario diyoduro (SMI<sub&gt; 2</sub&gt;) En THF se describe. El papel de los dos aditivos principales, a saber hexametilfosforamida (HMPA) y Ni (acac)<sub&gt; 2</sub&gt; Sm en reacciones mediadas se demuestra en la reacción de Sm-Barbier.

Preparación y uso de samario diyoduro (SMI<sub&gt; 2</sub&gt;) En Síntesis Orgánica: La función mecánica de HMPA y sales de Ni (II) en la reacción de samario Barbier

Although initially considered an esoteric reagent, SmI2 has become a common tool for synthetic organic chemists. SmI2 is generated through the addition of ...

preparation-use-samarium-diiodide-smi2-organic-synthesis-mechanistic

Research

JoVE Journal

Chemistry

Preparation and Use of Samarium Diiodide (SmI2) in Organic Synthesis: The Mechanistic Role of HMPA and Ni(II) Salts in the Samarium Barbier Reaction

32.8K vistas.  Lehigh University. Un procedimiento sencillo para la preparación de samario diyoduro (SMI 2) En THF se describe. El papel de los dos aditivos principales, a saber hexametilfosforamida (HMPA) y Ni (acac) 2 Sm en reacciones mediadas se demuestra en la reacción de Sm-Barbier.

Video: Preparation and Use of Samarium Diiodide SmI2 in Organic Synthesis: The Mechanistic Role of HMPA and NiII Salts in the Samarium Barbier Reaction

Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library

Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid phase by using combinatorial chemistry. One of the most well studied classes of peptidomimetics is peptoids. Peptoids are easy to synthesize and have been shown to be proteolysis-resistant and cell-permeable. Over the past decade, many useful protein ligands have been identified through screening of peptoid libraries. However, most of the ligands identified from peptoid libraries do not display high affinity, with rare exceptions. This may be due, in part, to the lack of chiral centers and conformational constraints in peptoid molecules. Recently, we described a new synthetic route to access peptide tertiary amides (PTAs). PTAs are a superfamily of peptidomimetics that include but are not limited to peptides, peptoids and N-methylated peptides. With side chains on both &#945;-carbon and main chain nitrogen atoms, the conformation of these molecules are greatly constrained by sterical hindrance and allylic 1,3 strain. (Figure 1) Our study suggests that these PTA molecules are highly structured in solution and can be used to identify protein ligands. We believe that these molecules can be a future source of high-affinity protein ligands. Here we describe the synthetic method combining the power of both split-and-pool and sub-monomer strategies to synthesize a sample one-bead one-compound (OBOC) library of PTAs.

Peptide tertiary amides (PTAs) are a superfamily of peptidomimetics that include but are not limited to peptides, peptoids and N-methylated peptides. Here we describe a synthetic method which combines&#160;both split-and-pool and sub-monomer strategies to synthesize a one-bead one-compound library of PTAs.

Síntesis Split-y-piscina y caracterización del péptido Terciario Amida Biblioteca

Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid ...

Investigación

Química

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Amide coupling reactions can be used to synthesize bispyridine-based ligands for use as bridging linkers in multinuclear platinum anticancer drugs. Isonicotinic acid, or its derivatives, are coupled to variable length diaminoalkane chains under an inert atmosphere in anhydrous DMF or DMSO with the use of a weak base, triethylamine, and a coupling agent, 1-propylphosphonic anhydride. The products precipitate from solution upon formation or can be precipitated by the addition of water. If desired, the ligands can be further purified by recrystallization from hot water. Dinuclear platinum complex synthesis using the bispyridine ligands is done in hot water using transplatin. The most informative of the chemical characterization techniques to determine the structure and gross purity of both the bispyridine ligands and the final platinum complexes is 1H NMR with particular analysis of the aromatic region of the spectra (7-9 ppm). The platinum complexes have potential application as anticancer agents and the synthesis method can be modified to produce trinuclear and other multinuclear complexes with different hydrogen bonding functionality in the bridging ligand.

This protocol describes the use of amide coupling reactions of isonicotinic acid and diaminoalkanes to form bridging ligands suitable for use in the synthesis of multinuclear platinum complexes, which combine aspects of the anticancer drugs BBR3464 and picoplatin.

Amida de reacción para la Síntesis de ligandos basados ​​en bispiridina y su complejación a Platinum como dinucleares Agentes anticancerígenos

Amide coupling reactions can be used to synthesize bispyridine-based ligands for use as bridging linkers in multinuclear platinum anticancer drugs. ...

Synthesis and Characterization of Functionalized Metal-organic Frameworks

Metal-organic frameworks have attracted extraordinary amounts of research attention, as they are attractive candidates for numerous industrial and technological applications. Their signature property is their ultrahigh porosity, which however imparts a series of challenges when it comes to both constructing them and working with them. Securing desired MOF chemical and physical functionality by linker/node assembly into a highly porous framework of choice can pose difficulties, as less porous and more thermodynamically stable congeners (e.g., other crystalline polymorphs, catenated analogues) are often preferentially obtained by conventional synthesis methods. Once the desired product is obtained, its characterization often requires specialized techniques that address complications potentially arising from, for example, guest-molecule loss or preferential orientation of microcrystallites. Finally, accessing the large voids inside the MOFs for use in applications that involve gases can be problematic, as frameworks may be subject to collapse during removal of solvent molecules (remnants of solvothermal synthesis). In this paper, we describe synthesis and characterization methods routinely utilized in our lab either to solve or circumvent these issues. The methods include solvent-assisted linker exchange, powder X-ray diffraction in capillaries, and materials activation (cavity evacuation) by supercritical CO2 drying. Finally, we provide a protocol for determining a suitable pressure region for applying the Brunauer-Emmett-Teller analysis to nitrogen isotherms, so as to estimate surface area of MOFs with good accuracy.

Synthesis, activation, and characterization of intentionally designed metal-organic framework materials is challenging, especially when building blocks are incompatible or unwanted polymorphs are thermodynamically favored over desired forms. We describe how applications of solvent-assisted linker exchange, powder X-ray diffraction in capillaries and activation via supercritical CO2 drying, can address some of these challenges.

Marcos de síntesis y caracterización de funcionalizado metal-orgánico

Metal-organic frameworks have attracted extraordinary amounts of research attention, as they are attractive candidates for numerous industrial and ...

Preparation and Use of Carbonyl-decorated Carbenes in the Activation of White Phosphorus

Here we present a protocol for the synthesis of two distinct carbonyl-decorated carbenes. Both carbenes can be prepared using nearly identical procedures in multi-gram scale quantities. The goal of this manuscript is to clearly detail how to handle and prepare these unique carbenes such that a synthetic chemist of any skill level can work with them. The two carbenes described are a diamidocarbene (DAC, carbene 1) and a monoamidoaminocarbene (MAAC 2). These carbenes are highly electron-deficient and as such display reactivity profiles that are atypical of more traditional N-heterocyclic carbenes. Additionally, these two carbenes only differ in their electrophilic character and not their steric parameters, making them ideal for studying how carbene electronics influence reactivity. To demonstrate this phenomenon, we are also describing the activation of white phosphorus (P4) using these carbenes. Depending on the carbene used, two very different phosphorus-containing compounds can be isolated. When the DAC 1 is used, a tris(phosphaalkenyl)phosphane can be isolated as the exclusive product. Remarkably however, when MAAC 2 is added to P4 under identical reaction conditions, an unexpected carbene-supported P8&#160;allotrope of phosphorus is isolated exclusively. Mechanistic studies demonstrate that this carbene-supported P8allotrope forms via a [2+2] cycloaddition dimerization of a transient diphosphene which has been trapped by treatment with 2,3-dimethyl-1,3-butadiene.

Here, we present a protocol for the synthesis of two carbonyl-decorated carbenes. The protocol makes these interesting compounds readily available to chemists of all skill levels. In addition to the synthesis of these two carbenes, their use in the activation of white phosphorus is also described.

Preparación y Uso de Carbenos carbonilo decorados en la activación de fósforo blanco

Here we present a protocol for the synthesis of two distinct carbonyl-decorated carbenes. Both carbenes can be prepared using nearly identical procedures ...

Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts

Ynones are a valuable functional group and building block in organic synthesis. Ynones serve as a precursor to many important organic functional groups and scaffolds. Traditional methods for the preparation of ynones are associated with drawbacks including harsh conditions, multiple purification steps, and the presence of unwanted byproducts. An alternative method for the straightforward preparation of ynones from acyl chlorides and potassium alkynyltrifluoroborate salts is described herein. The adoption of organotrifluoroborate salts as an alternative to organometallic reagents for the formation of new carbon-carbon bonds has a number of advantages. Potassium organotrifluoroborate salts are shelf stable, have good functional group tolerance, low toxicity, and a wide variety are straightforward to prepare. The title reaction proceeds rapidly at ambient temperature in the presence of a Lewis acid without the exclusion of air and moisture. Fair to excellent yields may be obtained via reaction of various aryl and alkyl acid chlorides with alkynyltrifluoroborate salts in the presence of boron trichloride.

The goal of this manuscript is to demonstrate a straightforward method for the preparation of ynones from acyl chloride and potassium alkynyltrifluoroborate salt starting materials. The one-pot reaction proceeds rapidly in the presence of boron trichloride without exclusion of air and moisture.

Sin metal Síntesis de Ynones de Acil cloruros y potasio Alkynyltrifluoroborate Sales

Ynones are a valuable functional group and building block in organic synthesis. Ynones serve as a precursor to many important organic functional groups ...

Synthesis and Reaction Chemistry of Nanosize Monosodium Titanate

This paper describes the synthesis and peroxide-modification of nanosize monosodium titanate (nMST), along with an ion-exchange reaction to load the material with Au(III) ions. The synthesis method was derived from a sol-gel process used to produce micron-sized monosodium titanate (MST), with several key modifications, including altering reagent concentrations, omitting a particle seed step, and introducing a non-ionic surfactant to facilitate control of particle formation and growth. The resultant nMST material exhibits spherical-shaped particle morphology with a monodisperse distribution of particle diameters in the range from 100 to 150&#160;nm. The nMST material was found to have a Brunauer-Emmett-Teller (BET) surface area of 285 m2g-1, which is more than an order of magnitude higher than the micron-sized MST. The isoelectric point of the nMST measured 3.34 pH units, which is a pH unit lower than that measured for the micron-size MST. The nMST material was found to serve as an effective ion exchanger under weakly acidic conditions for the preparation of an Au(III)-exchange nanotitanate. In addition, the formation of the corresponding peroxotitanate was demonstrated by reaction of the nMST with hydrogen peroxide.

The surfactant mediated sol-gel synthesis of nanosized monosodium titanate is described, along with preparation of the corresponding peroxide modified material. An ion-exchange reaction with Au(III) is also presented.

Síntesis y Reacción Química de tamaño nanométrico monosódico titanato

This paper describes the synthesis and peroxide-modification of nanosize monosodium titanate (nMST), along with an ion-exchange reaction to load the ...

Synthesis and Characterization of Supramolecular Colloids

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical properties for applications in photonics, drug delivery and coating technology. Here we present a new family of colloidal building blocks, coined supramolecular colloids, whose self-assembly is controlled through surface-functionalization with a benzene-1,3,5-tricarboxamide (BTA) derived supramolecular moiety. Such BTAs interact via directional, strong, yet reversible hydrogen-bonds with other identical BTAs. Herein, a protocol is presented that describes how to couple these BTAs to colloids and how to quantify the number of coupling sites, which determines the multivalency of the supramolecular colloids. Light scattering measurements show that the refractive index of the colloids is almost matched with that of the solvent, which strongly reduces the van der Waals forces between the colloids. Before photo-activation, the colloids remain well dispersed, as the BTAs are equipped with a photo-labile group that blocks the formation of hydrogen-bonds. Controlled deprotection with UV-light activates the short-range hydrogen-bonds between the BTAs, which triggers the colloidal self-assembly. The evolution from the dispersed state to the clustered state is monitored by confocal microscopy. These results are further quantified by image analysis with simple routines using ImageJ and Matlab. This merger of supramolecular chemistry and colloidal science offers a direct route towards light- and thermo-responsive colloidal assembly encoded in the surface-grafted monolayer.

A protocol for the synthesis and characterization of colloids coated with supramolecular moieties is described. These supramolecular colloids undergo self-assembly upon the activation of the hydrogen-bonds between the surface-anchored molecules by UV-light.

Síntesis y caracterización de supramoleculares Coloides

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical ...

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the development of antibody drug conjugates (ADCs) and nanomedicine, fluorescent microscopy and systems chemistry. For many of these applications, specificity of the bioconjugation method used is of prime concern. The Michael addition of maleimides with cysteine(s) on the target proteins is highly selective and proceeds rapidly under mild conditions, making it one of the most popular methods for protein bioconjugation.
We demonstrate here the modification of the only surface-accessible cysteine residue on yeast cytochrome c with a ruthenium(II) bisterpyridine maleimide. The protein bioconjugation is verified by gel electrophoresis and purified by aqueous-based fast protein liquid chromatography in 27% yield of isolated protein material. Structural characterization with MALDI-TOF MS and UV-Vis is then used to verify that the bioconjugation is successful. The protocol shown here is easily applicable to other cysteine - maleimide coupling of proteins to other proteins, dyes, drugs or polymers.

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

This protocol details the important steps required for the bioconjugation of a cysteine containing protein to a maleimide, including reagent purification, reaction conditions, bioconjugate purification and bioconjugate characterization.

Síntesis de Proteínas bioconjugados<em&gt; vía</em&gt; Química cisteína-maleimida

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the ...

Synthesis of Cyclic Polymers and Characterization of Their Diffusive Motion in the Melt State at the Single Molecule Level

We demonstrate a method for the synthesis of cyclic polymers and a protocol for characterizing their diffusive motion in a melt state at the single molecule level. An electrostatic self-assembly and covalent fixation (ESA-CF) process is used for the synthesis of the cyclic poly(tetrahydrofuran) (poly(THF)). The diffusive motion of individual cyclic polymer chains in a melt state is visualized using single molecule fluorescence imaging by incorporating a fluorophore unit in the cyclic chains. The diffusive motion of the chains is quantitatively characterized by means of a combination of mean-squared displacement (MSD) analysis and a cumulative distribution function (CDF) analysis. The cyclic polymer exhibits multiple-mode diffusion which is distinct from its linear counterpart. The results demonstrate that the diffusional heterogeneity of polymers that is often hidden behind ensemble averaging can be revealed by the efficient synthesis of the cyclic polymers using the ESA-CF process and the quantitative analysis of the diffusive motion at the single molecule level using the MSD and CDF analyses.

A protocol for the synthesis and characterization of diffusive motion of cyclic polymers at the single molecule level is presented.

Síntesis de polímeros cíclicos y caracterización de su movimiento difusivo en el estado fundido en la molécula de un solo nivel

We demonstrate a method for the synthesis of cyclic polymers and a protocol for characterizing their diffusive motion in a melt state at the single ...

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from benzimidazolium salts. Detailed and generalized protocols are also presented for testing the catalytic activity of such complexes in arylation and Suzuki-Miyaura cross-coupling reactions. Representative results are shown for the catalytic activity of the four complexes in arylation and Suzuki-Miyaura type reactions. For each of the reactions investigated, at least one of the four complexes successfully catalyzed the reaction, qualifying them as promising candidates for catalysis of many carbon-carbon bond-forming reactions. The protocols presented are general enough to be adapted for the synthesis, purification and catalytic activity testing of new palladium N-heterocyclic carbene complexes.

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from benzimidazolium salts. The complexes were tested for catalytic activity in arylation and Suzuki-Miyaura reactions. For each reaction investigated, at least one of the four complexes successfully catalyzed the reaction.

Paladio<em&gt; N</em&gt; -Heterocíclicos de los complejos de carburo: Síntesis a partir de sales de benzimidazolio y actividad catalítica en las reacciones de formación de enlaces carbono-carbono

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from ...

Preparación y uso de samario diyoduro (SMI

Resumen

Explorar más videos

Capítulos en este video

Síntesis Split-y-piscina y caracterización del péptido Terciario Amida Biblioteca

Amida de reacción para la Síntesis de ligandos basados en bispiridina y su complejación a Platinum como dinucleares Agentes anticancerígenos

Marcos de síntesis y caracterización de funcionalizado metal-orgánico

Preparación y Uso de Carbenos carbonilo decorados en la activación de fósforo blanco

Sin metal Síntesis de Ynones de Acil cloruros y potasio Alkynyltrifluoroborate Sales

Síntesis y Reacción Química de tamaño nanométrico monosódico titanato

Síntesis y caracterización de supramoleculares Coloides

Síntesis de Proteínas bioconjugados

Síntesis de polímeros cíclicos y caracterización de su movimiento difusivo en el estado fundido en la molécula de un solo nivel

Paladio

Preparación y uso de samario diyoduro (SMI

Resumen

Explorar más videos

Capítulos en este video

Síntesis Split-y-piscina y caracterización del péptido Terciario Amida Biblioteca

Amida de reacción para la Síntesis de ligandos basados ​​en bispiridina y su complejación a Platinum como dinucleares Agentes anticancerígenos

Marcos de síntesis y caracterización de funcionalizado metal-orgánico

Preparación y Uso de Carbenos carbonilo decorados en la activación de fósforo blanco

Sin metal Síntesis de Ynones de Acil cloruros y potasio Alkynyltrifluoroborate Sales

Síntesis y Reacción Química de tamaño nanométrico monosódico titanato

Síntesis y caracterización de supramoleculares Coloides

Síntesis de Proteínas bioconjugados

Síntesis de polímeros cíclicos y caracterización de su movimiento difusivo en el estado fundido en la molécula de un solo nivel

Paladio

Amida de reacción para la Síntesis de ligandos basados en bispiridina y su complejación a Platinum como dinucleares Agentes anticancerígenos