This work was supported by the UOIT start-up fund. We thank Mr. Matthew Baxter (UOIT) for his assistance in the laboratory.

1. Synthèse de Ynone <ol><li> En utilisant une balance analytique, peser 0,15 mmol de potassium souhaitée sel alkynyltrifluoroborate (1,5 équivalents) et ajouter dans un flacon propre équipé d&#39;une barre d&#39;agitation magnétique. </li><li> L&#39;utilisation d&#39;un piston de seringue en verre muni d&#39;une aiguille, ajouter 0,5 ml de DCM anhydre à la fiole pour donner une solution 0,3 M de trifluoroborate. NOTE: Comme il se agit d&#39;une nouvelle méthodologie, les réactions ont été réalisées pour la preuve de concept. Afin de réduire les déchets qu&#39;ils ont été effectués sur une petite échelle. La réaction peut être mise à l&#39;échelle pour produire des rendements plus élevés selon les besoins. </li><li> En utilisant une seringue en verre, ajouter 0,15 mmole d&#39;une solution 1,0 M de trichlorure de bore (1,5 équivalents) goutte à goutte 150 ul de la cuve de réaction à la température ambiante (20 ° C) sous agitation. Remettre le bouchon. Maintenir ou à fixer le récipient de réaction coiffé de telle sorte que la solution réactionnelle est inférieure à la ligne de flottaison dans le sonicateur. Soniquer la solution pendant 30 s à 20 ° C et une fréquence of 40 kHz. </li><li> Agiter la solution réactionnelle à la température ambiante (20 ° C) pendant 20 minutes supplémentaires. Selon la nature du matériau de départ alkynyltrifluoroborate, observer un changement de couleur. Un changement de couleur du blanc au beige ou brun foncé, rouge, ou pourpre est commun. </li><li> Ajouter 0,1 mmol du chlorure d&#39;acyle désiré (1,0 équivalent) dans le flacon à température ambiante (20 ° C) sous agitation. En variante, transférer le contenu du récipient de réaction dans un ballon chargé avec un barreau d&#39;agitation magnétique et 0,1 mmol de chlorure d&#39;acyle. Remettre le bouchon. Agiter la solution de réaction à température ambiante (20 ° C) pendant 30 min. NOTE: En règle générale, un changement à une couleur très sombre est une indication que la réaction se déroule. </li><li> L&#39;utilisation d&#39;une Chromatographie en couche mince (TLC) 34 surveiller la progression de la réaction par comparaison avec le standard de chlorure d&#39;acyle approprié. REMARQUE: Selon la nature des matériaux de départ, la réaction ne peut pas aller à son terme. L&#39;unchlorure cyl matériau de départ a été observé comme une tache de roulement plus élevé que le produit final pour tous les ynones préparés à ce jour en utilisant cette méthode. <ol><li> Préparer la norme de chlorure d&#39;acyle en diluant environ 10 mg du chlorure d&#39;acyle avec une matière de départ ml d&#39;acétate d&#39;éthyle dans un petit flacon. </li><li> L&#39;utilisation d&#39;un spotter TLC, repérer la solution de réaction et la norme sur la ligne de départ de la plaque TLC. Un co-spot à la fois la solution de réaction et de la norme peut être utile pour déterminer si il ya du matériel présent dans la solution de réaction encore partir. </li><li> Déterminer une phase mobile TLC appropriée par essais et erreurs. Pour la préparation des produits 1a, une phase mobile constituée de 1:30 acétate d&#39;éthyle: hexanes résultats en valeurs de Rf d&#39;environ 0,5 et 0,8 pour le produit de ynone et du chlorure de benzoyle matière de départ, respectivement. </li><li> Visualisez la plaque de CCM développé sous la lumière UV. Utilisez un crayon pour marquer toutes les taches visibles. </li></ol></li></ol> 2. Le traitement aqueux <ol><li> Stopper la réaction en ajoutant 1 ml d&#39;eau froide (environ 5 ° C) dans le récipient de réaction. En utilisant une pipette Pasteur, transférer la solution dans une ampoule à décanter propre. Diluer le contenu de l&#39;ampoule à décanter avec 10 ml d&#39;eau froide et extrait le produit une fois dans 15 ml d&#39;acétate d&#39;éthyle. </li><li> Jeter la couche aqueuse inférieure et laver la couche organique une fois avec 10 ml supplémentaires d&#39;eau et une fois avec 10 ml de saumure. Recueillir la phase organique dans un erlenmeyer propre et sèche avec du sulfate de magnésium. Filtrer la solution dans un ballon à fond rond propre en utilisant une filtration par gravité. </li></ol> 3. Purification de Ynone <ol><li> En utilisant la Chromatographie sur couche mince, déterminer une phase mobile appropriée pour Chromatographie éclair purification du produit. Un facteur de rétention (Rf) d&#39;environ 0,5 est généralement suffisante pour séparer le produit de départ tout en restanttion de matériaux et produits secondaires. NOTE: Dans le cas d&#39;une mauvaise séparation, un système solvant moins polaire peut être utilisé de telle sorte que le produit a une valeur Rf inférieure. En fonction de la polarité des matériaux de départ, un mélange hexanes: acétate d&#39;éthyle dans l&#39;intervalle de 30: 1 à 5: 1 est généralement approprié. </li><li> Préparer une colonne contenant de la silice humide avec la phase mobile appropriée. Ajouter une couche de sable au sommet de la colonne afin d&#39;éviter lors de l&#39;addition de la silice perturbateur du produit et éluant. </li><li> Evaporer la solution de traitement final au moyen d&#39;un évaporateur rotatif, la température du bain à 40 ° C et la rotation fixé à 120 tours par minute. Dissoudre le contenu de la fiole dans un 2 ml de phase mobile et soigneusement charger uniformément la solution sur la colonne. Assurez-vous que la silice est humide, mais la ligne de solvant ne dépasse pas la hauteur de la silice. Laisser un peu de solvant pour l&#39;élution de telle sorte que le produit se trouve sur la silice. Ajouter une petite quantité de phase mobile et répétez. </li><li> Remplissez le colUMN avec la phase mobile déterminé à l&#39;étape 3.1; dans le cas des produits 1a, à 30: 1 d&#39;hexanes: acétate d&#39;éthyle mélange est appropriée. On récupère les fractions dans des tubes à essai en utilisant une Chromatographie flash pour accélérer le processus de purification. Il suffit de brancher un adaptateur avec tube à une prise d&#39;air. Régler la pression d&#39;air de telle sorte que le flux d&#39;éluant à travers la colonne à un débit approprié. </li><li> Repérer chacune des fractions de colonne sur une plaque de CCM. Eventuellement, repérer la norme de chlorure d&#39;acyle comme référence. Développer le CCM en utilisant la phase mobile jugé approprié dans l&#39;étape 1.8. Marquez toutes les taches visibles sous lumière UV, notant que le produit devrait avoir un R f inférieure à la norme de chlorure d&#39;acyle. </li><li> Recueillir toutes les fractions contenant taches visibles dans un grand ballon à fond rond. Si plus d&#39;un spot avec un R f inférieure à celle du matériau de départ est présent, les recueillir dans des flacons séparés. On évapore le solvant en utilisant un évaporateur rotatif et on sèche la matière collectée under vide poussé pendant deux heures. </li><li> Si nécessaire, effectuer un lavage de pentane sur une petite colonne pour purifier en outre un produit de ynone préparé à partir d&#39;un matériau de départ pauvre en chlorure d&#39;acyle d&#39;électrons. A petite échelle, ceci peut être réalisé en utilisant une pipette Pasteur en tant que colonne. <ol><li> On dissout le produit dans un minimum de chloroforme, du DCM ou de l&#39;éther diéthylique et de la charge sur une colonne de silice par voie humide avec du pentane. Elute 1-2 longueurs de colonnes de pentane à travers la colonne et recueillir dans un bécher de déchets. </li><li> Éluer le produit de ynone pur de la colonne de pentane en utilisant de l&#39;éther diéthylique ou l&#39;acétate d&#39;éthyle. Recueillir éluant dans un ballon séparé, évaporer, et le placer sous vide poussé pendant un minimum de deux heures. Obtenir environ 10 mg de produit pour la caractérisation par spectroscopie RMN. </li></ol></li></ol> 4. Caractérisation des Ynone <ol><li> Caractériser et évaluer la pureté du produit final en utilisant 1 H et 13 spectroscopie RMN C. 34Typiquement, le déplacement chimique du carbone du groupe carbonyle apparaît près de 177 ppm sur le spectre 13 C-RMN. Les deux atomes de carbone du SP de la fonction ynone sont représentés par des pics caractéristiques proches de 87 et 93 ppm. </li><li> Utiliser la spectroscopie infrarouge 34 pour identifier le pic caractéristique du carbonyle du produit de ynone. Délocalisation d&#39;électrons à partir de la triple liaison adjacent provoque généralement le pic carbonyle apparaisse entre 1600 et 1650 cm -1, en ​​fonction des caractéristiques électroniques du composé. </li><li> Déterminer la masse moléculaire du produit et de valider davantage l&#39;identité en utilisant la spectrométrie de masse à haute résolution. 34 </li></ol>

<ol>
	<li>Bannwarth, P., Valleix, A., Gr&#233;e, D., Gr&#233;e, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Flexible+Synthesis+of+Pyrimidines+with+Chiral+Monofluorinated+and+Difluoromethyl+Side+Chains.">Flexible Synthesis of Pyrimidines with Chiral Monofluorinated and Difluoromethyl Side Chains.</a> J. Org. Chem. 74, 4646-4649 (2009).</li><li>Karpov, A. S., Merkul, E., Rominger, F., M&#252;ller, T. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Concise+Syntheses+of+Meridianins+by+Carbonylative+Alkynylation+and+a+Four&#8208;Component+Pyrimidine+Synthesis.">Concise Syntheses of Meridianins by Carbonylative Alkynylation and a Four&#8208;Component Pyrimidine Synthesis.</a> Angew. Chem. Int. Ed. 44, 6951-6956 (2005).</li><li>Arcadi, A., Aschi, M., Marinelli, F., Verdecchia, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pd-catalyzed+regioselective+hydroarylation+of+&#945;-(2-aminoaryl)-&#945;,+&#946;-ynones+with+organoboron+derivatives+as+a+tool+for+the+synthesis+of+quinolines:+experimental+evidence+and+quantum-chemical+calculations.">Pd-catalyzed regioselective hydroarylation of &#945;-(2-aminoaryl)-&#945;, &#946;-ynones with organoboron derivatives as a tool for the synthesis of quinolines: experimental evidence and quantum-chemical calculations.</a> Tetrahedron. 64, 5354-5361 (2008).</li><li>Lee, C. G., Lee, K. Y., Lee, S., Kim, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chemical+transformation+of+Baylis&#8211;Hillman+adducts:+the+reaction+of+methyl+3-arylamino-2-methylene-3-phenylpropanoates+in+polyphosphoric+acid.">Chemical transformation of Baylis&#8211;Hillman adducts: the reaction of methyl 3-arylamino-2-methylene-3-phenylpropanoates in polyphosphoric acid.</a> Tetrahedron. 61, 1493-1499 (2005).</li><li>Kirkham, J. D., Edeson, S. J., Stokes, S., Harrity, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+Ynone+Trifluoroborates+toward+Functionalized+Pyrazoles.">Synthesis of Ynone Trifluoroborates toward Functionalized Pyrazoles.</a> Org. Lett. 14, 5354-5357 (2012).</li><li>Mohamed Ahmed, M. S., Kobayashi, K., Mori, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=One-pot+construction+of+pyrazoles+and+isoxazoles+with+palladium-catalyzed+four-component+coupling.">One-pot construction of pyrazoles and isoxazoles with palladium-catalyzed four-component coupling.</a> Org. Lett. 7, 4487-4489 (2005).</li><li>Awuah, E., Capretta, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Access+to+Flavones+via+a+Microwave-Assisted,+One-Pot+Sonogashira&#8722;+Carbonylation&#8722;+Annulation+Reaction.">Access to Flavones via a Microwave-Assisted, One-Pot Sonogashira&#8722; Carbonylation&#8722; Annulation Reaction.</a> Org. Lett. 11, 3210-3213 (2009).</li><li>She, Z., 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=Synthesis+of+Trisubstituted+Isoxazoles+by+Palladium+(II)-Catalyzed+Cascade+Cyclization&#8211;Alkenylation+of+2-Alkyn-1-one+O-Methyl+Oximes.">Synthesis of Trisubstituted Isoxazoles by Palladium (II)-Catalyzed Cascade Cyclization&#8211;Alkenylation of 2-Alkyn-1-one O-Methyl Oximes.</a> J. Org. Chem. 77, 3627-3633 (2012).</li><li>Corey, E., Helal, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Novel+electronic+effects+of+remote+substituents+on+the+oxazaborolidine-catalyzed+enantioselective+reduction+of+ketones.">Novel electronic effects of remote substituents on the oxazaborolidine-catalyzed enantioselective reduction of ketones.</a> Tetrahedron Lett. 36, 9153-9156 (1995).</li><li>Matsumura, K., Hashiguchi, S., Ikariya, T., Noyori, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Asymmetric+transfer+hydrogenation+of+&#945;,+&#946;-acetylenic+ketones.">Asymmetric transfer hydrogenation of &#945;, &#946;-acetylenic ketones.</a> J. Am. Chem. Soc. 119, 8738-8739 (1997).</li><li>Midland, M. M., McDowell, D. C., Hatch, R. L., Tramontano, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduction+of.+alpha.,.+beta.-acetylenic+ketones+with+B-3-pinanyl-9-borabicyclo+[3.3.+1]+nonane.+High+asymmetric+induction+in+aliphatic+systems.">Reduction of. alpha.,. beta.-acetylenic ketones with B-3-pinanyl-9-borabicyclo [3.3. 1] nonane. High asymmetric induction in aliphatic systems.</a> J. Am. Chem. Soc. 102, 867-869 (1980).</li><li>Logue, M. W., Moore, G. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cuprous+trimethylsilylacetylide.+Preparation+and+reaction+with+acid+chlorides.">Cuprous trimethylsilylacetylide. Preparation and reaction with acid chlorides.</a> J. Org. Chem. 40, 131-132 (1975).</li><li>Normant, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Organocopper+(I)+Compounds+and+Organocuprates+in+Synthesis.">Organocopper (I) Compounds and Organocuprates in Synthesis.</a> Synthesis. , 63-80 (1972).</li><li>Logue, M. W., Teng, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Palladium-catalyzed+reactions+of+acyl+chlorides+with+(1-alkynyl)+tributylstannanes.+A+convenient+synthesis+for+1-alkynyl+ketones.">Palladium-catalyzed reactions of acyl chlorides with (1-alkynyl) tributylstannanes. A convenient synthesis for 1-alkynyl ketones.</a> J. Org. Chem. 47, 2549-2553 (1982).</li><li>Nahm, S., Weinreb, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=N-Methoxy-N-methylamides+as+effective+acylating+agents.">N-Methoxy-N-methylamides as effective acylating agents.</a> Tetrahedron Lett. 22, 3815-3818 (1981).</li><li>Baba, T., Kizuka, H., Handa, H., Ono, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reaction+of+ketones+or+aldehydes+with+1-alkynes+over+solid-base+catalysts.">Reaction of ketones or aldehydes with 1-alkynes over solid-base catalysts.</a> Appl. Catal., A. 194, 203-211 (2000).</li><li>Brown, H. C., Garg, C. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+simple+procedure+for+the+chromic+acid+oxidation+of+alcohols+to+ketones+of+high+purity.">A simple procedure for the chromic acid oxidation of alcohols to ketones of high purity.</a> J. Am. Chem. Soc. 83, 2952-2953 (1961).</li><li>Nishimura, T., Onoue, T., Ohe, K., Uemura, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Palladium+(II)-catalyzed+oxidation+of+alcohols+to+aldehydes+and+ketones+by+molecular+oxygen.">Palladium (II)-catalyzed oxidation of alcohols to aldehydes and ketones by molecular oxygen.</a> J. Org. Chem. 64, 6750-6755 (1999).</li><li>Pu, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Asymmetric+alkynylzinc+additions+to+aldehydes+and+ketones.">Asymmetric alkynylzinc additions to aldehydes and ketones.</a> Tetrahedron. 59, 9873-9886 (2003).</li><li>Kim, W., Park, K., Park, A., Choe, J., Lee, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pd-Catalyzed+Selective+Carbonylative+and+Non-carbonylative+Couplings+of+Propiolic+Acid:+One-Pot+Synthesis+of+Diarylalkynones.">Pd-Catalyzed Selective Carbonylative and Non-carbonylative Couplings of Propiolic Acid: One-Pot Synthesis of Diarylalkynones.</a> Org. Lett. 15, 1654-1657 (2013).</li><li>Kobayashi, T., Tanaka, M., Sakakura, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Palladium(ii)+Complex-catalysed+Formation+of+a-Keto+Acids+via+Double+Carbonylation+of+Organic.">Palladium(ii) Complex-catalysed Formation of a-Keto Acids via Double Carbonylation of Organic.</a> Halides J. Chem. Soc., Chem. Commun. , 837-838 (1985).</li><li>Mohamed Ahmed, M. S., Mori, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Carbonylative+Sonogashira+coupling+of+terminal+alkynes+with+aqueous+ammonia.">Carbonylative Sonogashira coupling of terminal alkynes with aqueous ammonia.</a> Org. Lett. 5, 3057-3060 (2003).</li><li>Vieira, A. 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=Nucleophilic+Addition+of+Potassium+Alkynyltrifluoroborates+to+d-Glucal+Mediated+by+BF3&#183;+OEt2:+Highly+Stereoselective+Synthesis+of+&#945;-C-glycosides.">Nucleophilic Addition of Potassium Alkynyltrifluoroborates to d-Glucal Mediated by BF3&#183; OEt2: Highly Stereoselective Synthesis of &#945;-C-glycosides.</a> Org. Lett. 10, 5215-5218 (2008).</li><li>Darses, S., Genet, J. -. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Potassium+organotrifluoroborates:+new+perspectives+in+organic+synthesis.">Potassium organotrifluoroborates: new perspectives in organic synthesis.</a> Chem. Rev. 108, 288-325 (2008).</li><li>Darses, S., Genet, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Potassium+trifluoro+(organo)+borates:+new+perspectives+in+organic+chemistry.">Potassium trifluoro (organo) borates: new perspectives in organic chemistry.</a> Eur. J. Org. Chem. 2003, 4313-4327 (2003).</li><li>Molander, G. A., Ellis, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Organotrifluoroborates:+Protected+Boronic+Acids+That+Expand+the+Versatility+of+the+Suzuki+Coupling+Reaction.">Organotrifluoroborates: Protected Boronic Acids That Expand the Versatility of the Suzuki Coupling Reaction.</a> Acc. Chem. Res. 40, 275-286 (2007).</li><li>Stefani, H. A., Cella, R., Vieira, A. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+advances+in+organotrifluoroborates+chemistry.">Recent advances in organotrifluoroborates chemistry.</a> Tetrahedron. 63, 3623-3658 (2007).</li><li>Matteson, D. S., Kim, G. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Asymmetric+alkyldifluoroboranes+and+their+use+in+secondary+amine+synthesis.">Asymmetric alkyldifluoroboranes and their use in secondary amine synthesis.</a> Org. Lett. 4, 2153-2155 (2002).</li><li>Dumas, A. M., Bode, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Synthesis of Acyltrifluoroborates. Org. Lett. 14, 2138-2141 (2012).</li><li>Dumas, A. M., Molander, G. A., Bode, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amide&#8208;Forming+Ligation+of+Acyltrifluoroborates+and+Hydroxylamines+in+Water.">Amide&#8208;Forming Ligation of Acyltrifluoroborates and Hydroxylamines in Water.</a> Angew. Chem. Int. Ed. 51, 5683-5686 (2012).</li><li>Mitchell, T. A., Bode, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+Dialkyl+Ethers+from+Organotrifluoroborates+and+Acetals.">Synthesis of Dialkyl Ethers from Organotrifluoroborates and Acetals.</a> J. Am. Chem. Soc. 131, 18057-18059 (2009).</li><li>Vo, C. -. V. T., Mitchell, T. A., Bode, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expanded+substrate+scope+and+improved+reactivity+of+ether-forming+cross-coupling+reactions+of+organotrifluoroborates+and+acetals.">Expanded substrate scope and improved reactivity of ether-forming cross-coupling reactions of organotrifluoroborates and acetals.</a> J. Am. Chem. Soc. 133, 14082-14089 (2011).</li><li>Zeng, J., Vedachalam, S., Xiang, S., Liu, X. -. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+C-Glycosylation+of+Organotrifluoroborates+with+Glycosyl+Fluorides+and+Its+Application+to+the+Total+Synthesis+of+(+)-Varitriol.">Direct C-Glycosylation of Organotrifluoroborates with Glycosyl Fluorides and Its Application to the Total Synthesis of (+)-Varitriol.</a> Org. Lett. 13, 42-45 (2010).</li><li>Lehman, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+student's+lab+companion:+laboratory+techniques+for+organic+chemistry:+standard+scale+and+microscale.">The student's lab companion: laboratory techniques for organic chemistry: standard scale and microscale.</a> Pearson College Div. , (2008).</li><li>Molander, G. A., Cavalcanti, L. N., Canturk, B., Pan, P. -. S., Kennedy, L. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficient+Hydrolysis+of+Organotrifluoroborates+via+Silica+Gel+and+Water.">Efficient Hydrolysis of Organotrifluoroborates via Silica Gel and Water.</a> 74, 7364-7369 (2009).</li><li>Molander, G. A., Ellis, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Organotrifluoroborates:+protected+boronic+acids+that+expand+the+versatility+of+the+Suzuki+coupling+reaction.">Organotrifluoroborates: protected boronic acids that expand the versatility of the Suzuki coupling reaction.</a> Acc. Chem. Res. 40, 275-286 (2007).</li><li>Calloway, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Friedel-Crafts+Syntheses.">The Friedel-Crafts Syntheses.</a> Chem. Rev. 17, 327-392 (1935).</li><li>Gore, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Friedel-Crafts+acylation+reaction+and+its+application+to+polycyclic+aromatic+hydrocarbons.">The Friedel-Crafts acylation reaction and its application to polycyclic aromatic hydrocarbons.</a> Chem. Rev. 55, 229-281 (1955).</li><li>Groves, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Friedel&#8211;Crafts+acylation+of+alkenes.">The Friedel&#8211;Crafts acylation of alkenes.</a> Chem. Soc. Rev. 1, 73-97 (1972).</li><li>Kim, B. J., Matteson, D. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conversion+of+alkyltrifluoroborates+into+alkyldichloroboranes+with+tetrachlorosilane+in+coordinating+solvents.">Conversion of alkyltrifluoroborates into alkyldichloroboranes with tetrachlorosilane in coordinating solvents.</a> Angew. Chem. 116, 3118-3120 (2004).</li><li>Thompson, L., Doraiswamy, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sonochemistry:+science+and+engineering.">Sonochemistry: science and engineering.</a> Ind. Eng. Chem. Res. 38, 1215-1249 (1999).</li></ol>

The authors declare that they have no competing financial interests.

Le tableau 1 illustre les mesures prises pour optimiser les conditions de la réaction de phénylacétylène trifluoroborate avec du chlorure de benzoyle pour former le produit de ynone correspondant. Initialement, les catalyseurs connus pour convertir organotrifluoroborates à organodifluoroboranes ont été testés. Malheureusement, gel de silice, 35 le tétrachlorure de silicium, le trifluorure de bore 36 et 31,32 ne favorise pas la formation de la ynone désirée (tableau 1, entrées 1 à 3). L&#39;utilisation de catalyseurs chlorés d&#39;acide de Lewis se est avérée plus fructueuse. Un faible rendement en ynone 1a désiré a été obtenu en présence d&#39;un catalyseur de fer (III) chlorure (tableau 1, entrée 4). Ensuite, l&#39;aluminium (III) chlorure a été étudiée en raison de sa capacité bien établie pour favoriser la formation d&#39;ions oxocarbénium dans acylations de Friedel-Crafts. 37 à 39 Le produit souhaité a été obtenu en un rendement de 62% lors d&#39;aluminium (III) un catalyseur de chlorure était empLoyed. En outre révélé que l&#39;optimisation de l&#39;air et de l&#39;humidité ont peu d&#39;effet sur ​​le rendement de la réaction (tableau 1, entrées 5-7). En conséquence, les réactions suivantes ont été effectuées dans de la verrerie séchée à la non-présence d&#39;air. Les tentatives visant à optimiser le solvant a révélé que le dichlorométhane (DCM) est particulièrement bien adaptée à la réaction (tableau 1, entrées 8-12). Des incohérences dans les résultats de réactions catalysées par l&#39;aluminium (III) chlorure incité l&#39;exploration de catalyseurs alternatifs. Disponible dans le commerce aluminium (III) chlorure hexahydraté était complètement inactif dans les conditions de réaction (tableau 1, entrée 13). Ce est un bon indicateur de la formation de l&#39;aluminium (III) chlorure hydrate inhibe la réaction. Le trichlorure de bore a été trouvé pour produire des rendements similaires avec une meilleure cohérence (tableau 1, entrée 14). Lors de l&#39;interaction du alkynyltriflu de potassiumoroborate avec le trichlorure de bore, une espèce organodichloroborane plus réactifs est formé. 40 Cette première étape est essentielle pour la réaction avec le chlorure d&#39;acyle et de la formation ynone de procéder. Comme sels organotrifluoroborate ne sont pas solubles dans du DCM, la réaction a lieu sous forme de mélange hétérogène. Après l&#39;addition de trichlorure de bore, la solution est soniquée afin de faciliter la formation des espèces réactives dichloroborane en augmentant la surface spécifique du sel de trifluoroborate disponible pour réagir. Application d&#39;ondes ultrasonores au mélange réactionnel provoque des effets mécaniques par le biais de la génération de bulles de cavitation. Durant la sonication, l&#39;effondrement des bulles de cavitation dans les résultats de fluide dans des zones localisées de températures et pressions élevées. 41 Les ondes de choc sont produites qui créent une turbulence microscopique résultant en une augmentation de l&#39;énergie cinétique des sels de trifluoroborate solides. L&#39;augmentation de l&#39;énergie du système pendant la sonication promotes fragmentation du sel résultant trifluoroborate augmentation de la surface disponible pour interagir avec le trichlorure de bore. La sonication du mélange réactionnel avant l&#39;addition de la matière de départ chlorure d&#39;acyle assure la formation efficace des espèces réactives alkynyldichloroborane sans avoir besoin de plusieurs conditions de désolidarisation ou de plus longs temps de réaction. La figure 2 illustre les résultats obtenus lorsque trifluoroborate phénylacétylène a été amené à réagir avec une variété de chlorures d&#39;acyle dans les conditions de réaction optimales. Neutre aromatique (1b, 1c) et aliphatique (1j-l) des chlorures d&#39;acyle correspondants ynones fournir les rendements de synthèse utiles. Ces chlorures d&#39;acyle portant des groupes donneurs d&#39;électrons (1d-g) fournissent d&#39;excellents rendements alors que les groupes attracteurs d&#39;électrons donnent des rendements relativement modestes (1h, 1i, 1m). Interestingly, lorsque le groupe attracteur d&#39;électrons est situé en position ortho (1i, 59%), une augmentation de rendement significative ne est observée par rapport à l&#39;analogue substitué par un chlorure d&#39;acyle (1h, 30%). L&#39;interaction stérique du substituant en position ortho peut forcer la fonction carbonyle en dehors du plan, compensant ainsi le caractère attracteur d&#39;électrons du cycle aromatique. Il est à noter que le chlorure de 4-bromobutyryle réagi pour donner le 1m produit désiré avec un rendement de 39%. À notre connaissance, ce est le premier protocole pour la synthèse de ynones à tolérer un groupe fonctionnel de bromure d&#39;alkyle. Occasionnellement, lorsque le chlorure d&#39;acyle produit de départ est neutre ou déficient en électrons, des impuretés aliphatiques apparaissent sur la RMN du proton. Cela peut nécessiter un lavage de pentane pour purifier davantage le produit. Alors que possible, il ne est pas économique d&#39;effectuer le lavage de pentane pendant la première étape de purificationepuis pentane est coûteux en comparaison à l&#39;hexane. Fin de l&#39;épuration secondaire séparément sur une plus petite échelle, comme une colonne de pipette Pasteur réduit considérablement la quantité de pentane requis. La figure 3 illustre l&#39;effet de l&#39;identité du sel alkynyltrifluoroborate sur le rendement de la réaction. En général, les dérivés des substituants donneurs d&#39;électrons portant le sel de phénylacétylène sur le noyau aromatique mis à réagir avec des chlorures d&#39;acyle aromatiques et aliphatiques pour produire les ynones souhaités dans rendements bons à excellents (2a-c, 3a-c). Sels alkynyltrifluoroborate aliphatiques révélés être des substrats moins réactifs. De modestes rendements ont été obtenus lorsque hexynyl- et sels cyclopentylethynyltrifluoroborate ont été mis à réagir avec des dérivés d&#39;électrons riches en chlorure de benzoyle (4a, 5a). En conclusion, un nouveau procédé pour la préparation of ynones de chlorures d&#39;acides et les sels de potassium alkynyltrifluoroborate a été développé. Les rendements obtenus pour la synthèse de ynones par cette tranche de méthode de modeste à excellente fonction de la nature du chlorure d&#39;acyle et trifluoroborate matières de départ. En général, les produits de départ portant les substituants donneurs d&#39;électrons sont soumis à la réaction plus facilement que les produits de départ portant des groupes fonctionnels électrophiles et neutres. La valeur de cette approche réside dans la simplicité et la tolérance groupe fonctionnel opérationnelle de la méthode. Cette réaction en un seul pot simple se déroule rapidement à la température ambiante en présence de trichlorure de bore sans exclusion de l&#39;air et de l&#39;humidité. Ce procédé commode peut être utilisée dans la préparation de ynones modeste en d&#39;excellents rendements à partir d&#39;une variété de chlorures d&#39;acyle et des sels alkynyltrifluoroborate.

The intention of this video is to demonstrate a straightforward approach for the preparation of compounds containing an ynone functional group from convenient starting materials. Ynones are valuable building blocks in organic chemistry that have been shown to have biomedical and material significance. Ynones are precursors to valuable organic functional groups including pyrimidines,1,2 quinolones,3 furans,4 pyrazoles,5,6 flavones,7 oximes,8 and chiral propargylic alcohols.9-11 A more convenient method for the preparation of ynones has been sought as a result of the drawbacks of traditional methods including poor functional group tolerance and tedious synthetic routes.
The reaction of metal12,13 and metalloid14 acetylides with acyl chlorides is one common route for the preparation of ynones. Alternatively, the synthesis of ynones from acyl chloride can be achieved via two-step procedures using Weinreb amides and organolithium or Grignard reagents.15 Another prevalent approach includes the addition of organolithium or Grignard reagents to an aldehyde, which is followed by the oxidation of a secondary alcohol to the corresponding ketone.16-19 Poor functional group tolerance of metal acetylides and the need to purify synthetic intermediates after each step are main deficiencies of the aforementioned methods. Transition-metal-catalyzed carbonylative couplings have recently emerged as an alternative approach for the preparation of ynones.20-22 Unfortunately, in addition to cost and toxicity associated with transition metals, metal-catalyzed carbonylative reactions often require elevated CO pressures and suffer from the presence of an undesired Sonogashira coupling byproduct. Given their utility in organic synthesis as well as the drawbacks associated with traditional synthetic methods, the development of a more straightforward method for the preparation of ynones is appealing.
Potassium organotrifluoroborate salts have recently emerged as versatile reagents in organic synthesis. Advantages including ease of preparation,23 inherent stability, low toxicity, and good functional group tolerance have made organotrifluoroborate salts attractive synthetic reagents.24-27 Organotrifluoroborate salts have been used primarily as a bench-stable equivalent of boronic acids for palladium-catalyzed Suzuki-Miyaura coupling.26 Recently, following a seminal work by Matteson and co-workers,28 Bode, Molander and others have highlighted the utility of organotrifluoroborates as reagents in non-metal catalyzed reactions.29-33 The field of transition-metal-free reactions of trifluoroborates is still in its infancy stage. Given the great potential for use of organotrifluoroborate salts in non-metal catalyzed organic synthesis, we sought to develop a novel method for the preparation of ynones from acyl chlorides and alkynyltrifluoroborate salts.

<table border="0" cellpadding="0" cellspacing="0" width="573">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Name of Material/ Equipment</td>
			<td style="width:71px;">Company</td>
			<td style="width:119px;">Catalog Number</td>
			<td style="width:167px;">Comments/Description</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Sonicator</td>
			<td style="width:71px;">VGT</td>
			<td style="width:119px;">1860QT</td>
			<td>Ultrasonic cleaner. Similar sonication devices may be used.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Dichloromethane</td>
			<td style="width:71px;">Sigma</td>
			<td style="width:119px;">270997</td>
			<td>Anhydrous</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Boron trichloride solution&#160;</td>
			<td style="width:71px;">Sigma</td>
			<td style="width:119px;">178934</td>
			<td>1M solution in DCM</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Acyl chloride</td>
			<td style="width:71px;">Sigma</td>
			<td style="width:119px;">Various</td>
			<td>Acyl chlorides from other suppliers such as Alfa Aesar may be used. Caution - refer to MSDS for safety information.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Potassium alkynyltrifluoroborate salt</td>
			<td style="width:71px;">N/A</td>
			<td style="width:119px;">N/A</td>
			<td>Synthesized23 from terminal alkyne</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Ethyl acetate</td>
			<td style="width:71px;">ACP</td>
			<td style="width:119px;">E-2000</td>
			<td>ACS grade</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Hexanes</td>
			<td style="width:71px;">ACP</td>
			<td style="width:119px;">H-3500</td>
			<td>ACS grade</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Pentane</td>
			<td style="width:71px;">Sigma</td>
			<td style="width:119px;">236705</td>
			<td>Anhydrous</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Magnesium sulfate</td>
			<td style="width:71px;">Sigma</td>
			<td style="width:119px;">M7506</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Filter paper</td>
			<td style="width:71px;">Whatman</td>
			<td style="width:119px;">1093 126</td>
			<td>Student grade. This speceific variety is not necessary.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Silica Gel 60</td>
			<td style="width:71px;">EMD</td>
			<td style="width:119px;">1.11567.9026</td>
			<td>Particle size 0.040-0.063</td>
		</tr>
	</tbody>
</table>

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.

Les efforts initiaux se sont concentrés autour de la préparation des ynone 1a du phénylacétylène trifluoroborate S1 et chlorure de benzoyle (Figure 1). Tableau 1 illustre les étapes d&#39;optimisation effectué, y compris le dépistage de différents acides de Lewis, des solvants, ainsi que l&#39;examen de l&#39;effet de l&#39;eau sur la réaction . Ensuite, l&#39;étendue de la réaction a été étudiée en soumettant phénylacétylène trifluoroborate des conditions optimisées en présence d&#39;une variété de chlorures d&#39;acyle (figure 2). Modest à d&#39;excellents rendements peuvent être obtenus en fonction de la nature du substrat de chlorure d&#39;acyle. L&#39;étendue de la réaction a en outre été évalué par la préparation de plusieurs exemples supplémentaires de sels alkynyltrifluoroborate. La figure 3 illustre des exemples d&#39;autres sels choisis alkynyltrifluoroborate qui peuvent être employés dans la préparation de ynones dans les conditions développées. Dérivés de phenylacetylene trifluoroborate électrons de palier substituants donneurs offertes les produits correspondants dans ynone rendements bons à excellents tandis dérivés aliphatiques de sels alkynyltrifluoroborate se sont avérés être procurant des rendements modestes légèrement moins réactifs. <img alt="Figure 1" src="/files/ftp_upload/52401/52401fig1highres.jpg" /> Figure 1: Préparation de 1a Ynone de phénylacétylène trifluoroborate S1 et chlorure de benzoyle schéma illustrant les conditions de préparation de 1a ynone y compris la formation de l&#39;intermédiaire réactif dichloroborane.. <img alt="Figure 2" src="/files/ftp_upload/52401/52401fig2highres.jpg" /> Figure 2:. Représentant une gamme de H ynone 1a RMN déplacements chimiques et les intégrations relatives des protons caractéristiques sont étiquetés. Figure 3:. Représentant 13 C spectre de ynone 1a RMN déplacements chimiques des atomes de carbone caractéristiques sont étiquetés. <img alt="Figure 4" src="/files/ftp_upload/52401/52401fig4highres.jpg" /> Figure 4:. Représentant spectre de ynone 1a obtenu par ionisation chimique à pression atmosphérique Le HRMS m / z de la valeur mesurée [M + H] + ion est signalé. <img alt="Figure 5" src="/files/ftp_upload/52401/52401fig5highres.jpg" /> Figure 5: Réactions de sel de phenylacetylenetrifluoroborate S1 avec des chlorures d&#39;acyle Structures et des rendements pour les produits fabriqués en faisant varier l&#39;identité.de la matière de départ chlorure d&#39;acyle sont illustrés. Les réactions ont été effectuées avec 1 équivalent de chlorure d&#39;acyle, 1,5 équiv phenylacetylenetrifluoroborate S1 de potassium, le trichlorure de bore et 1,5 équiv. <img alt="Figure 6" src="/files/ftp_upload/52401/52401fig6highres.jpg" /> Figure 6: Réactions de diverses. Alkynyltrifluoroborates avec des chlorures d&#39;acyle structures et des rendements des produits obtenus en faisant varier l&#39;identité du matériau de départ sont illustrés alkynyltrifluoroborate. Les réactions ont été effectuées avec 1 équivalent de chlorure d&#39;acyle, 2,5 équiv sel de potassium et 2,5 équiv organotrifluoroborate trichlorure de bore. <table border="0" cellpadding="0" cellspacing="0"><tbody><tr><td> Entrée </td><td> Acide de Lewis </td><td> Acide de Lewis (équiv) </td><td> Conditions </td><td> Rendement (%) </td></tr><tr><td> 1 b &lt;/ Sup&gt; </td><td> SiO 2 </td><td> 16,5 </td><td> CH 2 Cl 2 </td><td> 0 </td></tr><tr><td> 2 </td><td> SiCl 4 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> trace </td></tr><tr><td> 3 </td><td> BF 3 · OEt 2 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> trace </td></tr><tr><td> 4 b </td><td> FeCl 3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 24 </td></tr><tr><td> 5 c </td><td> AlCl 3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 62 </td></tr><tr><td> 6 d </td><td> AlCl 3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 66 </td></tr><tr><td> 7 e </td><td> AlCl 3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 60 </td></tr><tr><td> 8 </td><td> AlCl 3 </sub&gt; </td><td> 1 </td><td> THF </td><td> trace </td></tr><tr><td> 9 </td><td> AlCl 3 </td><td> 1 </td><td> toluène </td><td> trace </td></tr><tr><td> 10 </td><td> AlCl 3 </td><td> 2 </td><td> ClCH 2 CH 2 Cl </td><td> 33 </td></tr><tr><td> 11 </td><td> AlCl 3 </td><td> 1 </td><td> DMSO </td><td> trace </td></tr><tr><td> 12 </td><td> AlCl 3 </td><td> 2 </td><td> acétonitrile </td><td> trace </td></tr><tr><td> 13 </td><td> AlCl 3 · 6H 2 O </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 0 </td></tr><tr><td> 14 b </td><td> BCl 3 </td><td> 1,5 </td><td> CH 2 Cl 2 </td><td> 67 </td></tr><tr><td> 15 </td><td> BBr3 </td><td> 1 </td><td> CH 2 Cl 2 </td><td> 20 </td></tr></tbody></table><strong&gt; Tableau 1:. L&#39;optimisation des conditions pour la préparation de 1a ynone un rendement de produit 1a lors de la variation de conditions de réaction et catalyseur acide de Lewis. Un réactions ont été conduites avec 1 équivalent de chlorure de benzoyle et 1 équivalent phenylacetylenetrifluoroborate de potassium S1. B 1.5 équiv S1. C des conditions anhydres. D La réaction a été effectuée dans de la verrerie non séché sous air. E conditions anhydres + 1 pi d&#39;eau.

Watch this Scientific Journal Video about Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts at JoVE.com

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

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 ...

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11.1K vues.  University of Ontario Institute of Technology. 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.

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

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

Although initially considered an esoteric reagent, SmI2 has become a common tool for synthetic organic chemists. SmI2 is generated through the addition of molecular iodine to samarium metal in THF.1,2-3 It is a mild and selective single electron reductant and its versatility is a result of its ability to initiate a wide range of reductions including C-C bond-forming and cascade or sequential reactions. SmI2 can reduce a variety of functional groups including sulfoxides and sulfones, phosphine oxides, epoxides, alkyl and aryl halides, carbonyls, and conjugated double bonds.2-12 One of the fascinating features of SmI-2-mediated reactions is the ability to manipulate the outcome of reactions through the selective use of cosolvents or additives. In most instances, additives are essential in controlling the rate of reduction and the chemo- or stereoselectivity of reactions.13-14 Additives commonly utilized to fine tune the reactivity of SmI2 can be classified into three major groups: (1) Lewis bases (HMPA, other electron-donor ligands, chelating ethers, etc.), (2) proton sources (alcohols, water etc.), and (3) inorganic additives (Ni(acac)2, FeCl3, etc).3
Understanding the mechanism of SmI2 reactions and the role of the additives enables utilization of the full potential of the reagent in organic synthesis. The Sm-Barbier reaction is chosen to illustrate the synthetic importance and mechanistic role of two common additives: HMPA and Ni(II) in this reaction. The Sm-Barbier reaction is similar to the traditional Grignard reaction with the only difference being that the alkyl halide, carbonyl, and Sm reductant are mixed simultaneously in one pot.1,15 Examples of Sm-mediated Barbier reactions with a range of coupling partners have been reported,1,3,7,10,12 and have been utilized in key steps of the synthesis of large natural products.16,17 Previous studies on the effect of additives on SmI2 reactions have shown that HMPA enhances the reduction potential of SmI2 by coordinating to the samarium metal center, producing a more powerful,13-14,18 sterically encumbered reductant19-21 and in some cases playing an integral role in post electron-transfer steps facilitating subsequent bond-forming events.22 In the Sm-Barbier reaction, HMPA has been shown to additionally activate the alkyl halide by forming a complex in a pre-equilibrium step.23
Ni(II) salts are a catalytic additive used frequently in Sm-mediated transformations.24-27 Though critical for success, the mechanistic role of Ni(II) was not known in these reactions. Recently it has been shown that SmI2 reduces Ni(II) to Ni(0), and the reaction is then carried out through organometallic Ni(0) chemistry.28
These mechanistic studies highlight that although the same Barbier product is obtained, the use of different additives in the SmI2 reaction drastically alters the mechanistic pathway of the reaction. The protocol for running these SmI2-initiated reactions is described.

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

A straightforward procedure for the preparation of samarium diiodide (SmI2) in THF is described. The role of two main additives namely hexamethylphosphoramide (HMPA) and Ni(acac)2 in Sm mediated reactions is demonstrated in the Sm-Barbier reaction.

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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Chimie

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization

The traditional strategy for the introduction of chemical functionalities is the use of solid-phase synthesis by appending suitably modified phosphoramidite precursors to the nascent chain. However, the conditions used during the synthesis and the restriction to rather short sequences hamper the applicability of this methodology. On the other hand, modified nucleoside triphosphates are activated building blocks that have been employed for the mild introduction of numerous functional groups into nucleic acids, a strategy that paves the way for the use of modified nucleic acids in a wide-ranging palette of practical applications such as functional tagging and generation of ribozymes and DNAzymes. One of the major challenges resides in the intricacy of the methodology leading to the isolation and characterization of these nucleoside analogues.
	
	In this video article, we present a detailed protocol for the synthesis of these modified analogues using phosphorous(III)-based reagents. In addition, the procedure for their biochemical characterization is divulged, with a special emphasis on primer extension reactions and TdT tailing polymerization. This detailed protocol will be of use for the crafting of modified dNTPs and their further use in chemical biology.

The protocol described herein aims to explain and abridge the numerous obstacles in the way of the intricate route leading to modified nucleoside triphosphates. Consequently, this protocol facilitates both the synthesis of these activated building-blocks and their availability for practical applications.

Nucléosidiques Triphosphates - de la synthèse à caractérisation biochimique

The  traditional strategy for the introduction of chemical functionalities is the  use of solid-phase synthesis by appending suitably modified ...

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 ...

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 ...

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 ...

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine

Amino alcohols are versatile compounds with a wide range of applications. For instance, they have been used as chiral scaffolds in organic synthesis. Their synthesis by conventional organic chemistry often requires tedious multi-step synthesis processes, with difficult control of the stereochemical outcome. We present a protocol to enzymatically synthetize amino alcohols starting from the readily available L-lysine in 48 h. This protocol combines two chemical reactions that are very difficult to conduct by conventional organic synthesis. In the first step, the regio- and diastereoselective oxidation of an unactivated C-H bond of the lysine side-chain is catalyzed by a dioxygenase; a second regio- and diastereoselective oxidation catalyzed by a regiodivergent dioxygenase can lead to the formation of the 1,2-diols. In the last step, the carboxylic group of the alpha amino acid is cleaved by a pyridoxal-phosphate (PLP) decarboxylase (DC). This decarboxylative step only affects the alpha carbon of the amino acid, retaining the hydroxy-substituted stereogenic center in a beta/gamma position. The resulting amino alcohols are therefore optically enriched. The protocol was successfully applied to the semipreparative-scale synthesis of four amino alcohols. Monitoring of the reactions was conducted by high performance liquid chromatography (HPLC) after derivatization by 1-fluoro-2,4-dinitrobenzene. Straightforward purification by solid-phase extraction (SPE) afforded the amino alcohols with excellent yields (93% to &#62;95%).

Chiral amino alcohols are versatile molecules for use as scaffolds in organic synthesis. Starting from L-lysine, we synthesize amino alcohols by an enzymatic cascade reaction combining diastereoselective C-H oxidation catalyzed by dioxygenase followed by cleavage of the carboxylic acid moiety of the corresponding hydroxyl amino acid by a decarboxylase.

Réactions de Cascade enzymatique pour la synthèse des aminoalcools chiraux de L-lysine

Amino alcohols are versatile compounds with a wide range of applications. For instance, they have been used as chiral scaffolds in organic synthesis. ...

Synthesis of Substrate-Bound Au Nanowires Via an Active Surface Growth Mechanism

Advancing synthetic capabilities is important for the development of nanoscience and nanotechnology. The synthesis of nanowires has always been a challenge, as it requires asymmetric growth of symmetric crystals. Here, we report a distinctive synthesis of substrate-bound Au nanowires. This template-free synthesis employs thiolated ligands and substrate adsorption to achieve the continuous asymmetric deposition of Au in solution at ambient conditions. The thiolated ligand prevented the Au deposition on the exposed surface of the seeds, so the Au deposition only occurs at the interface between the Au seeds and the substrate. The side of the newly deposited Au nanowires is immediately covered with the thiolated ligand, while the bottom facing the substrate remains ligand-free and active for the next round of Au deposition. We further demonstrate that this Au nanowire growth can be induced on various substrates, and different thiolated ligands can be used to regulate the surface chemistry of the nanowires. The diameter of the nanowires can also be controlled with mixed ligands, in which another &#34;bad&#34; ligand could turn on the lateral growth. With the understanding of the mechanism, Au nanowire-based nanostructures can be designed and synthesized.

We report a solution-based method to synthesize substrate-bound Au nanowires. By tuning the molecular ligands used during the synthesis, the Au nanowires can be grown from various substrates with different surface properties. Au nanowire-based nanostructures can also be synthesized by adjusting the reaction parameters.

Synthèse de nanofils Au substrat-bondissent Via un mécanisme de croissance de Surface Active

Advancing synthetic capabilities is important for the development of nanoscience and nanotechnology. The synthesis of nanowires has always been a ...

Synthesis and Characterization of Amphiphilic Gold Nanoparticles

Gold nanoparticles covered with a mixture of 1-octanethiol (OT) and 11-mercapto-1-undecane sulfonic acid (MUS) have been extensively studied because of their interactions with cell membranes, lipid bilayers, and viruses. The hydrophilic ligands make these particles colloidally stable in aqueous solutions and the combination with hydrophobic ligands creates an amphiphilic particle that can be loaded with hydrophobic drugs, fuse with the lipid membranes, and resist nonspecific protein adsorption. Many of these properties depend on nanoparticle size and the composition of the ligand shell. It is, therefore, crucial to have a reproducible synthetic method and reliable characterization techniques that allow the determination of nanoparticle properties and the ligand shell composition. Here, a one-phase chemical reduction, followed by a thorough purification to synthesize these nanoparticles with diameters below 5 nm, is presented. The ratio between the two ligands on the surface of the nanoparticle can be tuned through their stoichiometric ratio used during synthesis. We demonstrate how various routine techniques, such as transmission electron microscopy (TEM), nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), and ultraviolet-visible (UV-Vis) spectrometry, are combined to comprehensively characterize the physicochemical parameters of the nanoparticles.

Amphiphilic gold nanoparticles can be used in many biological applications. A protocol to synthesize gold nanoparticles coated by a binary mixture of ligands and a detailed characterization of these particles is presented.

Synthèse et caractérisation des nanoparticules d'or amphiphiles

Gold nanoparticles covered with a mixture of 1-octanethiol (OT) and 11-mercapto-1-undecane sulfonic acid (MUS) have been extensively studied because of ...

Hierarchical and Programmable One-Pot Oligosaccharide Synthesis

This article presents a general experimental protocol for programmable one-pot oligosaccharide synthesis and demonstrates how to use Auto-CHO software for generating potential synthetic solutions. The programmable one-pot oligosaccharide synthesis approach is designed to empower fast oligosaccharide synthesis of large amounts using thioglycoside building blocks (BBLs) with the appropriate sequential order of relative reactivity values (RRVs). Auto-CHO is a cross-platform software with a graphical user interface that provides possible synthetic solutions for programmable one-pot oligosaccharide synthesis by searching a BBL library (containing about 150 validated and &#62;50,000 virtual BBLs) with accurately predicted RRVs by support vector regression. The algorithm for hierarchical one-pot synthesis has been implemented in Auto-CHO and uses fragments generated by one-pot reactions as new BBLs. In addition, Auto-CHO allows users to give feedback for virtual BBLs to keep valuable ones for further use. One-pot synthesis of stage-specific embryonic antigen 4 (SSEA-4), which is a pluripotent human embryonic stem cell marker, is demonstrated in this work.

This protocol demonstrates how to use the Auto-CHO software for hierarchical and programmable one-pot synthesis of oligosaccharides. It also describes the general procedure for RRV determination&#160;experiments and one-pot glycosylation of SSEA-4.

Synthèse hiérarchique et programmable d'oligosaccharide d'un pot

This article presents a general experimental protocol for programmable one-pot oligosaccharide synthesis and demonstrates how to use Auto-CHO software for ...