RAF remercie la National Science Foundation (CHE-0844946) pour le soutien de ce travail.

1. Synthèse des SmI 2 (0,1 M) <ol><li> Flamme sécher de 50 ml flacon à fond rond et le rincer avec de l&#39;argon. Ajouter une barre d&#39;agitation et de couvrir le ballon avec septa. Peser le samarium métallique (0,2 g, 1,3 mmol) et ajouter dans le ballon, le ballon de nouveau rinçage à l&#39;argon. </li><li> Ajouter 10 ml sec, soigneusement dégazé le tétrahydrofurane (THF), suivie par des cristaux d&#39;iode (0,254 g, 2,0 mmol). Ajouter un ballon d&#39;argon à travers la cloison, ce qui maintient une pression positive d&#39;une atmosphère d&#39;argon à la réaction. </li><li> Agiter la solution vigoureusement à température ambiante pendant plus de 3 heures. Comme SmI 2 est générée la solution passe par une série de modifications de la couleur jaune orange suivi d&#39;(45 min) et vert (1 h) qui se transformera en bleu. </li><li> La dernière couleur bleu marine est une indication que le samarium fois ionisé s&#39;est formé. Afin d&#39;assurer une conversion complète, agiter la solution pendant au moins 3 heures avant de l&#39;utiliser SmI 2 dans la synthèse. </li></ol> 2. SaMarium Barbier de réaction hexaméthylphosphoramide (HMPA) Addition <ol><li> Pour rendre le SmI 2-HMPA complexe, prendre le fraîchement préparée SmI 2 sous atmosphère d&#39;argon (10 ml, 0,1 M, 1,0 mmol) et ajouter 1,75 ml de HMPA (10 équiv., 10 mmol) par le biais d&#39;une seringue, goutte à goutte, sous argon. Il se forme une couleur pourpre profond. </li><li> Séparément dans un endroit propre, sec, flacon sous atmosphère d&#39;argon, ajouter iodododecane (0,45 mmol, 110 pl), 3-pentanone (0,45 mmol, 48 pl) et 2 ml de THF sec. </li><li> Ajouter le mélange de solution de substrat goutte à goutte au SmI 2 / HMPA complexe. </li><li> Dans les 5 minutes d&#39;agitation, la couleur pourpre va commencer à regarder nuageux, indiquant la fin de la réaction. </li><li> Après la réaction est terminée, exposer la solution à de l&#39;air pour la trempe; agitation sur les changements de couleur jaune pour d&#39;autres. </li><li> La réaction est ensuite traité par un lavage avec une solution aqueuse saturée de chlorure d&#39;ammonium. Ajouter la solution dans une ampoule à décanter et ajouter l&#39;éther diéthylique (5 ml). Après agitation vigoureuse retirerla couche organique supérieure, ajoutez plus de l&#39;éther diéthylique. Extraire à partir de la phase aqueuse deux fois plus, puis de combiner l&#39;ensemble des couches organiques. </li><li> Laver la phase organique avec une solution saturée de thiosulfate de sodium aqueux. Retirer la couche inférieure aqueuse, suivi d&#39;un lavage à l&#39;eau puis avec de la saumure lavage final. Obtenir la phase organique supérieure et d&#39;ajouter du sulfate de magnésium pour absorber toute quantité d&#39;eau présente dernier dans la solution. </li><li> Faire passer la solution à travers un bouchon de Florisil afin d&#39;éliminer l&#39;excès HMPA. </li><li> Concentrer la solution sur un évaporateur rotatif pour obtenir Barbier produit. Le produit a été identifié par GCMS et RMN 1 H 23. </li></ol> 3. Samarium Barbier de réaction Ni (acac) 2 Catalyst <ol><li> Peser Ni (acac) 2 (1% en mole, 0,01 mmol, 0,0026 g) et ajouter à un endroit propre, sec, flacon contenant 3 ml de THF dégazé sous argon. Ajouter le Ni (acac) 2 solution à travers une seringue à une s fraîchement préparélution de 0,1 M SmI 2 (1,0 mmol, 10 ml). </li><li> Séparément dans un endroit propre, sec, flacon sous atmosphère d&#39;argon, ajouter iodododecane (0,45 mmol, 110 pl), 3-pentanone (0,45 mmol, 48 pl) et 2 ml de THF sec. </li><li> Ajouter la solution de substrat goutte à goutte au SmI 2 / Ni mélange. </li><li> Dans les quinze minutes d&#39;agitation, la couleur bleue se dissipe pour former une couleur jaune-vert indiquant la fin de la réaction. </li><li> Après la réaction est terminée, exposer la solution à de l&#39;air pour la trempe; agitation sur les changements de couleur jaune pour d&#39;autres. Travailler jusqu&#39;à la réaction par lavage avec 0,1 M aq. L&#39;acide chlorhydrique (3 ml). Ajouter la solution dans une ampoule à décanter et ajouter l&#39;éther diéthylique (5 ml). </li><li> Laver la phase organique selon le protocole décrit précédemment par une solution aqueuse de thiosulfate de sodium, de l&#39;eau et de la saumure, puis séchée sur sulfate de magnésium. Concentrer la solution pour obtenir Barbier produit. Le produit peut être identifié par GCMS et RMN 1 H 28. </sup&gt; </li></ol>

<ol>
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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>

Aucun conflit d&#39;intérêt déclaré.

Une procédure simple pour générer SmI 2 solution et son application en synthèse organique en utilisant deux des additifs les plus courants est présenté ici. Les deux exemples décrits dépeindre l&#39;importance de la compréhension des mécanismes de la réaction d&#39;affiner la réactivité de SmI 2. La connaissance du fondement du mécanisme de réaction permet l&#39;utilisation de ce réactif à être adapté par les chimistes de synthèse, conformément aux exigences de leur réaction. Ce single réducteur électronique homogène est facile à manipuler et peuvent être achetés auprès de sources commerciales. Bien que le protocole ci-dessus est simple lorsque vous avez terminé dans des conditions inertes, certaines des procédures de dépannage courantes sont les suivantes: (a) s&#39;assurer que le THF est correctement dégazée et sec, (b) si le métal Sm a eu une exposition prolongée à l&#39;air, il pourrait avoir un oxydé couche extérieure, meuler le métal avec un mortier et pestal pour exposer la surface métallique propre, (c)flamme sécher toute la verrerie et frais sous atmosphère d&#39;argon, (d) l&#39;argon est préférable atmosphère inerte d&#39;azote plus, comme l&#39;a par la suite été montré pour interagir avec le métal, (e) La présence d&#39;un excès de Sm-métal permet de maintenir la concentration de SmI 2, (f) resublime les cristaux d&#39;iode.

<table border="1"><tbody><tr><td> Nom du réactif </td><td> Entreprise </td><td> Numéro de catalogue </td><td> Commentaires (optionnel) </td></tr><tr><td> Samarium métallique </td><td> Acros </td><td> 29478-0100 </td><td> Maille -40, 99,9% (sur la base des métaux) </td></tr><tr><td> THF </td><td> OmniSolv </td><td> TX0282-1 </td><td> Purifiée par le système de purification Technologies innovantes solvant. Alternativement, il peut être dégazé par la méthode de libre-pompe-dégel </td></tr><tr><td> Iode </td><td> Alfa Aesar </td><td> 41955-22 </td><td> Cristaux Resublimed, 99,8% </td></tr><tr><td> Iodododecane </td><td> Acros </td><td> 25009-0250 </td><td> 98% </td></tr><tr><td> 3-pentanone </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%, Distiller de CaO sous argon </td></tr><tr><td> Nii 2 </td><td> Alfa Aesar </td><td> 22893 </td><td> 99,5% (sur la base des métaux) </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

Bien qu&#39;initialement considéré comme un réactif ésotérique, SmI 2 est devenu un outil commun pour la chimie organique de synthèse. SmI 2 est générée par l&#39;ajout d&#39;iode moléculaire au samarium métallique dans le THF. 1,2-3 Il s&#39;agit d&#39;un réducteur électronique doux et sélectif unique et sa polyvalence est le résultat de sa capacité à initier un large éventail de réductions, y compris liaison CC- et formant cascade ou réactions successives. SmI 2 peut réduire une variété de groupes fonctionnels y compris les sulfoxydes et sulfones, les oxydes de phosphines, les époxydes, les halogénures d&#39;alkyle et d&#39;aryle, les carbonyles, et doubles liaisons conjuguées. 12.02 Un des aspects les plus fascinants de SMI-2-réactions médiées est la capacité de manipuler le résultat de réactions par l&#39;utilisation sélective des co-solvants ou additifs. Dans la plupart des cas, les additifs sont essentiels pour contrôler le taux de réduction et les réactions de chimio-ou la stéréosélectivité d&#39;. 13-14 additifs commonly utilisé pour ajuster la réactivité de SmI 2 peuvent être classés en trois grands groupes: (1) des bases de Lewis (HMPA, d&#39;autres donneurs d&#39;électrons des ligands chélateurs, des éthers, etc), sources de protons (2) (alcools, l&#39;eau, etc ), et (3) des additifs inorganiques (Ni (acac) 2, FeCl 3, etc.) 3 Comprendre le mécanisme de SMI 2 réactions et le rôle des additifs permet une utilisation du plein potentiel du réactif en synthèse organique. La réaction Sm-Barbier est choisi pour illustrer l&#39;importance et le rôle de synthèse mécaniste de deux additifs communs: HMPA et Ni (II) dans cette réaction. La réaction Sm-Barbier est similaire à la réaction de Grignard traditionnelle avec la seule différence étant que l&#39;halogénure d&#39;alkyle, carbonyle et réducteur Sm sont mélangés simultanément dans un pot. 1,15 Des exemples de réactions Barbier Sm-médiation avec un éventail de partenaires de couplage ont été signalés, 1,3,7,10,12 et ont été utilized dans les étapes clés de la synthèse des grands produits naturels. 16,17 études antérieures sur l&#39;effet des additifs sur SMI 2 réactions ont montré que HMPA améliore le potentiel de réduction des SmI 2 en coordonnant, dans le centre de samarium métallique, produisant un plus puissant, 13-14,18 stériquement encombrée réducteur 19-21 et dans certains cas, jouent un rôle essentiel dans la post-transfert d&#39;électrons étapes suivantes facilitant formation de liaison des événements. 22 Dans la réaction Sm-Barbier, HMPA a été démontré que plus activer l&#39;halogénure d&#39;alkyle en formant un complexe à une étape de pré-équilibre. 23 Ni (II) les sels sont un additif catalytique utilisé fréquemment dans Sm-médiation transformations. 24-27 Bien que critique pour le succès, le rôle mécaniste de Ni (II) n&#39;était pas connu dans ces réactions. Récemment, il a été montré que SmI 2 réduit Ni (II) en Ni (0), et la réaction est alors réalisée par organometallic Ni (0) chimie 28. Ces études mécanistiques souligner que bien que le produit Barbier on obtient le même, l&#39;utilisation de différents additifs dans l&#39;SmI 2 réaction modifie radicalement la voie mécanistique de la réaction. Le protocole pour l&#39;exécution de ces SmI 2-initiés réactions est décrite.

La figure 1 illustre la réaction du samarium Barbier. En l&#39;absence d&#39;additifs, la réaction de Sm-médiation prend 72 heures, cédant 69% du produit désiré avec les restants étant des matières premières. Avec l&#39;ajout de 10 ou plus équivalent. de HMPA la réaction est presque quantitative et complète en quelques minutes. 15,23 Avec l&#39;ajout de 1 mol% Ni (acac) 2, la réaction est terminée en 15 minutes, avec un rendement de 97% 28. Lorsque HMPA est ajouté à SmI 2, les déplace cosolvant le THF coordonnés pour former SmI 2 - (HMPA) 4. Avec l&#39;addition d&#39;autant plus HMPA (6-10 éq.), Les ions iodure sont déplacées dans la sphère externe (figure 2). 19-21 études mécanistiques indiquent que lorsque HMPA est utilisé dans la réaction de Sm-Barbier le co-solvant interagit également avec un halogénure d&#39;alkyle du substrat formant un complexe qui allonge la liaison carbone-halogénure, l&#39;activation de l&#39;artpecies rendant plus sensible à la réduction de Sm (figure 3). Grâce à cette compréhension détaillée des rôles de HMPA, un mécanisme pour la réaction Sm-Barbier à HMPA a été proposé (figure 4). 23 L&#39;halogénure d&#39;alkyle-HMPA complexe formé dans une étape de pré-équilibre est réduite par Sm / HMPA pour former le radical dans l&#39;étape de détermination de taux. Le radical subit une réduction supplémentaire pour former une espèce qui organosamarium couple avec le groupe carbonyle et sur protonation conduit au produit final. Dans le cas de Ni (II) un additif, SmI 2 réduit initialement Ni (II) en Ni (0) de préférence à la réduction de l&#39;un des substrats. Basé sur des études cinétiques et mécanistiques le mécanisme suivant a été proposé (figure 5) 28. Après réduction par SmI 2, inserts espèces du Ni soluble (0) dans le lien halogénure d&#39;alkyle formant une espèce organonickel. Poussé par la nature hautement oxophile de Sm (III)<html> , Transmétallation pour former un intermédiaire organosamarium communiqués de Ni (II) dans le cycle catalytique. Le organosamarium puis les couples avec le groupe carbonyle, et après protonation forme l&#39;alcool désiré tertiaire. Il a également été observé que Ni (0) nanoparticules sont formées par Sm-médiation réduction de Ni (II), mais ces particules sont avérés inactifs et la source de la désactivation du catalyseur. <img alt="Figure 1" fo:content-width="4in" fo:src="/files/ftp_upload/4323/4323fig1highres.jpg" src="/files/ftp_upload/4323/4323fig1.jpg" /> Figure 1. Samarium Barbier réaction avec iodododecane et la 3-pentanone. <img alt="Figure 2" fo:content-width="4in" fo:src="/files/ftp_upload/4323/4323fig2highres.jpg" src="/files/ftp_upload/4323/4323fig2.jpg" /> Figure 2. SmI 2-HMPA complexe. ontenu &quot;fo: keep-together.within pages =&quot; always &quot;&gt; <img alt="Figure 3" fo:content-width="3.5in" fo:src="/files/ftp_upload/4323/4323fig3highres.jpg" src="/files/ftp_upload/4323/4323fig3.jpg" /> Figure 3. HMPA et complexe iodure d&#39;alkyle. <img alt="Figure 4" fo:content-width="4.5in" fo:src="/files/ftp_upload/4323/4323fig4highres.jpg" src="/files/ftp_upload/4323/4323fig4.jpg" /> Figure 4. Mécanisme proposé pour la réaction de samarium Barbier avec HMPA excès. <img alt="Figure 5" fo:content-width="4in" fo:src="/files/ftp_upload/4323/4323fig5highres.jpg" src="/files/ftp_upload/4323/4323fig5.jpg" /> Figure 5. Mécanisme proposé pour la réaction de samarium Barbier contenant du Ni catalytique (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 procédé simple pour la préparation de samarium diiodure (SMI<sub&gt; 2</sub&gt;) Dans du THF est décrit. Le rôle des deux principaux additifs savoir hexaméthylphosphoramide (HMPA) et Ni (acac)<sub&gt; 2</sub&gt; Sm dans les réactions à médiation se manifeste dans la réaction Sm-Barbier.

Préparation et utilisation de samarium diiodure (SMI<sub&gt; 2</sub&gt;) In Organic Synthesis: Le rôle mécanistique de HMPA et Ni (II) Sels dans la réaction Samarium Barbier

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

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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

32.6K vues.  Lehigh University. Un procédé simple pour la préparation de samarium diiodure (SMI 2) Dans du THF est décrit. Le rôle des deux principaux additifs savoir hexaméthylphosphoramide (HMPA) et Ni (acac) 2 Sm dans les réactions à médiation se manifeste dans la réaction Sm-Barbier.

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

Synthesis, Cellular Delivery and In vivo Application of Dendrimer-based pH Sensors

The development of fluorescent indicators represented a revolution for life sciences. Genetically encoded and synthetic fluorophores with sensing abilities allowed the visualization of biologically relevant species with high spatial and temporal resolution. Synthetic dyes are of particular interest thanks to their high tunability and the wide range of measureable analytes. However, these molecules suffer several limitations related to small molecule behavior (poor solubility, difficulties in targeting, often no ratiometric imaging allowed). In this work we introduce the development of dendrimer-based sensors and present a procedure for pH measurement in vitro, in living cells and in vivo. We choose dendrimers as ideal platform for our sensors for their many desirable properties (monodispersity, tunable properties, multivalency) that made them a widely used scaffold for several biomedical devices. The conjugation of fluorescent pH indicators to the dendrimer scaffold led to an enhancement of their sensing performances. In particular dendrimers exhibit reduced cell leakage, improved intracellular targeting and allow ratiometric measurements. These novel sensors were successfully employed to measure pH in living HeLa cells and in vivo in mouse brain.

Synthesis, Cellular Delivery and In vivo Application of Dendrimer-based pH Sensors

Fluorescence sensors are powerful tools in life science. Here we describe a methodology to synthesize and use dendrimer-based fluorescent sensors to measure pH in living cells and in vivo. The dendritic scaffold enhances the properties of conjugated fluorescent dyes leading to improved sensing properties.

Synthèse, Livraison cellulaire et<em&gt; In vivo</em&gt; Utilisation de capteurs de pH à base de dendrimères

The development of  fluorescent indicators represented a revolution for life sciences. Genetically  encoded and synthetic fluorophores with sensing ...

Recherche

Chimie

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.

Amide Réaction de couplage pour la synthèse de ligands à base de bispyridine et leur complexation Platinum comme dinucléaires agents anticancéreux

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.

Cadres de synthèse et la caractérisation de fonctionnalisé métal-organique

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.

Préparation et utilisation des carbènes carbonyle décorées dans l&#39;activation de phosphore blanc

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.

Synthèse sans métal de Ynones de Acyl chlorures et du potassium Alkynyltrifluoroborate Sels

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.

Synthèse et Réaction Chimie des nanoparticules monosodique titanate

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.

Synthèse et caractérisation de supramoléculaires Colloids

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.

Synthèse des bioconjugués protéiques<em&gt; via</em&gt; Cystéine-maléimide 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 ...

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.

Synthèse des polymères cycliques et caractérisation de leur mouvement Diffusive dans l&#39;État Melt à la molécule unique 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 ...

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.

Palladium<em&gt; N</em&gt; - Complexes de carbène hétérocyclique: synthèse des sels de benzimidazolium et activité catalytique dans les réactions de formation de liaison carbone-carbone

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