O financiamento para este projecto do Fundo American Chemical Society Petroleum Research (52488-DNI1) e da Universidade da Carolina do Norte em Greensboro é reconhecido agradecimento. Agradecemos também o Dr. Terry Nilo (UNCG) para emprestar-nos o vidro apropriado para essas experiências. Consultoria e edição de vídeo por Aaron Glancy também é reconhecido.

1. Síntese de fenil HIAT <ol><li> Equipar um frasco de 100 ml de fundo redondo, seco, com um agitador magnético e tem o balão sob uma atmosfera de árgon. Prenda o frasco para uma posição e coloque-o em um banho cryogen de acetonitrilo e de dióxido de carbono sólido pellets. Nota: O fluido criogénico deve ser aproximadamente de -45 ° C. </li><li> Adicionar 10 ml de diclorometano seco ao balão de frio e permitir que o solvente para se equilibrar com a temperatura do fluido criogénico. Nota: O excesso de espaço superior no frasco é importante para a adição de éter dietílico depois de forçar a precipitação. </li><li> Pesar 0,35 g (1 equiv.) De cyanophenyliodonium triflato e rapidamente transferi-lo para o balão frio. Nota: Os sólidos devem ser bastante insolúvel a esta temperatura. </li><li> Tara a massa de um seringa vazia e, em seguida, usá-lo pesar 0,37 g (1 equiv.) De phenylethynyltributyltin. </li><li> Injectar a phenylethynyltributyltin na solução fria. Nota: A dissolução de sólidos é uma indicação de queo HIAT foi formado. O tempo aproximado para a dissolução é de 30 min. </li><li> Adicionar éter dietílico e hexano a fim de forçar a precipitação do produto. Nota: Se um precipitado não forma, evapora-se o solvente sob pressão reduzida e adicionar uma mistura de éter dietílico e hexano para forçar a precipitação do HIAT. </li><li> Equipar um frasco de vácuo com um funil de Buchner e verter a solução sobre o funil de filtração. </li><li> Recolher os sólidos e armazenar frio em um recipiente opaco. </li></ol> 2. Síntese de n-pentil HIAT <ol><li> Equipar um frasco de 250 ml de fundo redondo de três tubuladuras seco com um agitador magnético e tem o balão sob uma atmosfera de árgon. Prenda o frasco para uma posição e coloque-o em um banho cryogen de acetonitrilo e de dióxido de carbono sólido pellets. Nota: O fluido criogénico deve ser aproximadamente de -45 ° C. </li><li> Montar um aparelho de filtração de Schlenk no balão de modo a que a filtração pode ser efectuada rapidamente e a uma temperatura friatura. Graxa e prender juntos cada junta do aparelho. Nota: O sistema de filtragem pode ser construída por vários meios, mas é importante que o sistema tem a capacidade de empurrar com gás inerte e puxar com um vácuo através de um filtro de vidro. </li><li> Adicionar 10 ml de diclorometano seco ao balão de frio e permitir que o solvente para se equilibrar com a temperatura do fluido criogénico. Nota: O excesso de espaço superior no frasco é importante para a adição de hexano, depois de forçar a precipitação. </li><li> Pesar 0,35 g (1 equiv.) De cyanophenyliodonium triflato e rapidamente transferi-lo para o balão frio. Nota: Os sólidos devem ser bastante insolúvel a esta temperatura. </li><li> Tara a massa de um seringa vazia e, em seguida, usá-lo pesar 0,44 g (1 equiv.) De tributilteno heptino. </li><li> Injectar a heptino tributilteno na solução fria. Nota: A dissolução de sólidos é uma indicação de que o HIAT foi formado. O tempo aproximado para a dissolução é de 30 min. </li><li> Injetar 75 ml de hexane no espaço livre adicional do balão de modo a formar um precipitado. </li><li> Coloque o frasco de coleta a vácuo. </li><li> Soltar o aparelho do suporte e incline-a cuidadosamente despeje a solução para o filtro de vidro. Abra o frasco de coleta a vácuo para puxar o líquido através. Nota: Não permitir que o vácuo para puxar o ar para dentro do recipiente. </li><li> Desmontar o aparelho e raspar os sólidos fora do filtro uma vez que a filtração é completa. Uma vez que o sólido é removido a partir do filtrado é menos sensível a temperatura do ar e podem ser manuseados e aberto para o ar. </li><li> Recolher os sólidos e armazenar frio em um recipiente opaco. </li></ol> 3. OH Inserção de Cyanocarbenes Feito de Phenyl HIAT <ol><li> Equipar um frasco de 50 ml de fundo redondo, seco, com um agitador magnético e tem o balão sob uma atmosfera de árgon. Fixar o frasco com uma placa de agitação e injectar 20 ml de metanol seco ao balão. </li><li> Pesar 0,300 g (1 equiv.) Do synthesi anteriormentezed Fenil HIAT rapidamente e adicioná-lo ao balão. </li><li> Adicionar 0,047 g (1 equiv.) De azida de sódio ao balão. Nota: A solução escurece ao longo do tempo e azoto gasoso é gerado através da formação cyanocarbene. </li><li> Deixe a reacção continuar durante o tempo que ocorre a formação de bolhas. O tempo aproximado para a conclusão é de 20 min. </li><li> Expor a solução ao ar e evapora-se o solvente utilizando pressão reduzida. </li><li> Adiciona-se diclorometano ao líquido residual e efectuar a extracção aquosa para remover o triflato de sódio. Recolher as fases orgânicas de diclorometano e seca-se com sulfato de sódio anidro. </li><li> Decantar a solução e evapora-se a pressão reduzida. </li><li> Realizar cromatografia em coluna para purificar o produto cyanocarbene. </li></ol> 4. A ciclopropanação Cyanocarbene reacção usando Fenil HIAT <ol><li> Pesar 0,125 g (1 equiv.) De azida tetrabutilamio em um porta-luvas e colocá-lo em um 10 ml seco eq balão de fundo redondouipped com um agitador magnético. </li><li> Tampe a 10 ml balão de fundo redondo contendo azida tetrabutilamio, retire-a do porta-luvas, e colocá-lo em uma placa de agitação sob gás argônio usando uma linha Schlenk. </li><li> Adicionar 1,0 ml de estireno ao balão e permitir ao balão com agitação. Nota: A azida não precisa de se dissolver. </li><li> Rapidamente adicionar 0,200 g (1 equiv.) De Fenil HIAT a esta suspensão e colocar o septo de volta no frasco, que está ligado a uma linha Schlenk. Nota: A solução deve escurecer imediatamente e gerar gás nitrogênio por formação cyanocarbene. </li><li> Deixar a reacção continuar durante o tempo que ocorre a formação de bolhas. O tempo aproximado para a conclusão é de um minuto. </li><li> Após as bolhas de ter parado, expor a solução ao ar e realizar cromatografia em coluna para purificar o produto. </li></ol>

<ol>
	<li>Hyatt, I. F. D., Meza-Avi&#241;a, M. E., Croatt, M. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alkynes+&amp;+Azides:+Not+Just+for+Click+Reactions.">Alkynes &amp; Azides: Not Just for Click Reactions.</a> Synlett. 23 (20), 2869-2874 (2012).</li><li>Meza-Avi&#241;a, M. E., Patel, M. K., Lee, C. B., Dietz, T. J., Croatt, M. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+Formation+of+1,5-Substituted+Sulfonyl+Triazoles+Using+Acetylides+and+Sulfonyl+Azides.">Selective Formation of 1,5-Substituted Sulfonyl Triazoles Using Acetylides and Sulfonyl Azides.</a> Organic Letters. 13 (12), 2984-2987 (2011).</li><li>Hyatt, I. F. D., Croatt, M. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reactions+of+Hypervalent+Iodonium+Alkynyl+Triflates+with+Azides:+Generation+of+Cyanocarbenes.">Reactions of Hypervalent Iodonium Alkynyl Triflates with Azides: Generation of Cyanocarbenes.</a> Angewandte Chemie International Edition. 51 (30), 7511-7514 (2012).</li><li>Banert, K., Hagedorn, M., Wutke, J., Ecorchard, P., Schaarschmidt, D., Lang, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Elusive+ethynyl+azides:+trapping+by+1,3-dipolar+cycloaddition+and+decomposition+to+cyanocarbenes.">Elusive ethynyl azides: trapping by 1,3-dipolar cycloaddition and decomposition to cyanocarbenes.</a> Chemical Communications. 46 (23), 4058-4060 (2010).</li><li>Koumbis, A., Kyzas, C., Savva, A., Varvolis, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Formation+of+New+Alkynyl(phenyl)iodonium+Salts+and+Their+Use+in+the+Synthesis+of+Phenylsulfonyl+Indenes+and+Acetylenes.">Formation of New Alkynyl(phenyl)iodonium Salts and Their Use in the Synthesis of Phenylsulfonyl Indenes and Acetylenes.</a> Molecules. 10 (10), 1340-1350 (2005).</li><li>Banert, K., Arnold, R., Hagedorn, M., Thoss, P., Auer, A. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=1-Azido-1-Alkynes:+Synthesis+and+Spectroscopic+Characterization+of+Azidoacetylene.">1-Azido-1-Alkynes: Synthesis and Spectroscopic Characterization of Azidoacetylene.</a> Angewandte Chemie International Edition. 51 (30), 7515-7518 (2012).</li><li>Zhdankin, V. V., Stang, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chemistry+of+Polyvalent+Iodine.">Chemistry of Polyvalent Iodine.</a> Chemical Reviews. 108 (12), 5299-5358 (2008).</li><li>Br&#228;se, S., Banert, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Organic Azides - Syntheses and Applications. , (1002).</li><li>Stang, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alkynyl-+and+Alkenyl(phenyl)iodonium+Compounds.">Alkynyl- and Alkenyl(phenyl)iodonium Compounds.</a> Angewandte Chemie International Edition. 31 (3), 274-285 (2003).</li><li>Hembre, R. T., Scott, C. P., Norton, J. R. <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+olefins+to+ditriflates+by+&#956;-oxobis[(trifluoromethanesulfonato)(phenyl)iodine.">Conversion of olefins to ditriflates by &#956;-oxobis[(trifluoromethanesulfonato)(phenyl)iodine.</a> Journal of Organic Chemistry. 52 (16), 3650-3654 (1987).</li><li>Stang, P. J., Surber, B. W., Chen, Z., Roberts, K. A., Anderson, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acetylenic+Esters.+Preparation+and+Mechanism+of+Formation+of+Alkynyl+Tosylates+and+Mesylates+via+Tricoordinate+Iodonium+Species.">Acetylenic Esters. Preparation and Mechanism of Formation of Alkynyl Tosylates and Mesylates via Tricoordinate Iodonium Species.</a> Journal of the American Chemical Society. 109 (1), 228-235 (1987).</li><li>Zhdankin, V. V., Crittell, C. M., Stang, P. J., Zefirov, N. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+general+approach+to+unsymmetrical+tricoordinate+iodinanes:+Single+step+preparation+of+mixed+iodosobenzene+sulfonates+Phl(X)OSO2R,+via+reaction+of+iodosobenzene+with+Me3SiX.">A general approach to unsymmetrical tricoordinate iodinanes: Single step preparation of mixed iodosobenzene sulfonates Phl(X)OSO2R, via reaction of iodosobenzene with Me3SiX.</a> Tetrahedron Letters. 31 (34), 4821-4824 (1990).</li><li>Lee, H., Jung, Y., Yoon, Y., Kim, B. G., Kim, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Angularly+Fused+Triquinanes+from+Linear+Substrates+through+Trimethylenemethane+Diyl+[2+++3]+Cycloaddition+Reaction.">Angularly Fused Triquinanes from Linear Substrates through Trimethylenemethane Diyl [2 + 3] Cycloaddition Reaction.</a> Organic Letters. 12 (11), 2672-2674 (2010).</li><li>Beauchard, A., Phillips, V. A., Lloyd, M. D., Threadgill, M. D. <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+2-(4-carboxybutenyl)-+and+2-(4-carboxybutynyl)-cyclopentene-1-carboxamides.">Synthesis of 2-(4-carboxybutenyl)- and 2-(4-carboxybutynyl)-cyclopentene-1-carboxamides.</a> Tetrahedron. 65 (39), 8176-8184 (2009).</li><li>Kitamura, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+Alternative+Synthesis+of+Alkynyl(phenyl)iodonium+Triflates+Using+(Diacetoxyiodo)benzene+and+Alkynylsilanes.">An Alternative Synthesis of Alkynyl(phenyl)iodonium Triflates Using (Diacetoxyiodo)benzene and Alkynylsilanes.</a> Synthesis. 10, 1416 (1998).</li><li>Bouma, M. J., Olofsson, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=General+One-Pot+Synthesis+of+Alkynyliodonium+Salts+and+Alkynyl+Benziodoxolones+from+Aryl+Iodides.">General One-Pot Synthesis of Alkynyliodonium Salts and Alkynyl Benziodoxolones from Aryl Iodides.</a> Chemistry A European Journal. 18, 14242 (2012).</li><li>Williamson, B. L., Stang, P. J., Preparation Arif, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+Structure,+and+Diels-Alder+Cycloaddition+Chemistry+of+&#946;-Functionalized+Alkynyl(phenyl)iodonium+Salts.">Molecular Structure, and Diels-Alder Cycloaddition Chemistry of &#946;-Functionalized Alkynyl(phenyl)iodonium Salts.</a> Journal of the American Chemical Society. 115 (7), 2590-2597 (1993).</li></ol>

Os autores declaram que não têm interesses financeiros concorrentes.

Hipervalente iodónio alcinilo triflatos, ou HIATs, são formados e pode ser feito reagir com fontes de azida para formar cyanocarbenes. É muito importante que todas as precauções necessárias sejam tomadas, já que muitos dos reagentes e intermediários mostrados neste vídeo são potencialmente explosiva e altamente tóxico. Apesar do elevado grau de reactividade pode ser perigosa se mal preparada, é mostrado neste vídeo que a reactividade inerente dos compostos pode ser aproveitada por captura dos cyanocarbenes ...

A evolução contínua da química orgânica depende da concepção e desenvolvimento de novas reações. Em particular, a descoberta de novas reações que permitem rotas sintéticas inimagináveis ​​ter significado final. Para este fim, o nosso grupo desejado para converter dois átomos de carbono de um alcino e um azoto de uma azida em uma cyanocarbene. Uma Essa transformação previamente desconhecido que permitem um aumento significativo na complexidade molecular desde o cyanocarbene reactivo que reagem rapidamente ainda mais. O esforço inicial era usar um alcino nucleofílico e electrof azida, mas triazóis foram eficientemente formado, neste caso, ao contrário de cyanocarbenes. 2 Usando uma abordagem umpolung, o segundo método usa uma azida e alcino nucleofílico e electrof produtos resultantes das reacções de cyanocarbene são felizmente formado neste caso. 3 Existem muitas fontes de azida nucleofílica, no entanto, são alcinos electrofmuito menos comum. O grupo de Klaus Banert relatado anteriormente a prova de conceito para essa reação usando um cloreto de alquinilo, 4, mas o nosso grupo eo grupo Banert independente e contemporaneamente determinou que hipervalente iodónio alquinilo triflatos (HIATs) são muito melhores electrophiles para as razões de estabilidade e reactividade. 3,6 Descrevemos aqui a síntese, isolamento, e a reacção destes HIATs com azidas de formar e reagir in situ como cyanocarbenes. Várias medidas de segurança devem ser considerados antes de prosseguir com estas experiências. Alguns triflatos alcinilo hipervalente iodónio são instáveis ​​e se decompõem, algures violentamente, quando exposto ao ar e à luz. 7 Para formar o cyanocarbene intermédia, o procedimento requer a utilização de fontes de azida. Azidas são explosivas e altamente tóxico. 8 adequado equipamento de protecção individual deve ser usado quando manusear esses materiais, especialmente organoestânico,e toda a manipulação dos reagentes deve ocorrer em capuzes adequadamente ventiladas. O cyanocarbene é um poderoso e instável intermediário reativo. Tome cuidado para realizar experimentos inicialmente em pequenas escalas para que a evolução de gás nitrogênio é controlável e nunca realizar estas reações em sistemas fechados. Se scale-up da reação é desejado, sugerimos o uso de um escudo de segurança. A síntese de muitos HIATs ter sido previamente publicada, incluindo o uso do reagente de Zefirov 9,10, e o reagente de Koser, 9,11 no entanto, este vídeo será usando o reagente triflato cyanophenyliodonium 9,12 (Figura 1). Cyanophenyliodonium triflato foi sintetizado com base em uma preparação de literatura anteriormente apresentada. 13 O reagente reage com o trialquil-estanho alcinos modificados 14 para formar o produto desejado. Após a HIAT é sintetizado e isolado que pode ser feito reagir com azida para formarum intermediário reactivo cyanocarbene (Figura 2). Existem vários outros métodos que podem ser utilizados para sintetizar os alcinos iodónio, tais como a utilização de silanos alcinilo 15 e ésteres borónicos alcinilo 16, mas o método em que o vídeo foi escolhido porque, na nossa experiência, seria melhor eficiência e rendimento. O nosso mecanismo proposto de 3,5 (Figura 3) para esta reacção envolve a adição de uma fonte de azida para o β-carbono do alcino, formando desse modo um-ileto de iodo que se decompõe para iodobenzeno e uma vinilideno-carbeno. O vinilideno-carbeno pode então passar por um 1,2-rearranjo através de migração ou o grupo R ou azida, para se obter um alcinilo-azida. O alcinilo-azida em seguida, faz a extrusão de diazoto para formar um cyanocarbene que pode reagir com um substrato. Deve notar-se que pode haver formação de uma espécie alcenilo triflato hipervalente iodónio, dependendo das condições. O subproduto éfavorecida a temperaturas mais baixas, em solventes próticos, onde a protonação do iodo-ileto é mais rápido do que o rearranjo da azida de alcinilo. Outro produto possível que ocorre durante as reacções de inserção de OH é um éter de vinilo, onde o vinilideno-carbeno é preso antes do rearranjo de o alcinilo-azida pode ocorrer. A propensão para formar este éter vinílico é determinado pelo grupo R. Uma das principais vantagens desta reacção é que, depois de o carbeno reage, o grupo nitrilo resultante é uma pega conveniente para posterior funcionalização. Muitos sintões pode ser previsto com esta método e produtos diferentes podem ser formadas com os mesmos substratos. Controlando-se a mistura do produto com a temperatura, concentração, e o grupo R do alcino é necessário. 3 Com visão adequada de como cyanocarbenes comportar, o método apresenta um meio viável para adicionar rapidamente complexidade químico para formar uma molécula alvo. Os exemplos de como o cyanocarbene reage incluem inserção de OH, onde o átomo de oxigénio nucleofílico do álcool ataca o carbeno e, em seguida, a transferência de protões ocorre, dimetilsulfóxido complexação, onde o carbeno combina com o átomo de enxofre, e onde o carbeno ciclopropanação reage com um alceno.

<table border="1">
<tbody>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Reagent</td>
 </tr>
 <tr>
 <td>Phenyl acetylene</td>
 <td>Acros</td>
 <td>AC152461000</td>
 <td></td>
 </tr>
 <tr>
 <td>Tri-n-butyltin chloride</td>
 <td>Acros</td>
 <td>139351000</td>
 <td></td>
 </tr>
 <tr>
 <td>Lithium bis(trimethysilyl)amide</td>
 <td>Acros</td>
 <td>347701000</td>
 <td></td>
 </tr>
 <tr>
 <td>Iodobenzene diacetate</td>
 <td>Acros</td>
 <td>176560250</td>
 <td></td>
 </tr>
 <tr>
 <td>Trimethylsilyl cyanide</td>
 <td>Aldrich</td>
 <td>212849</td>
 <td>Extremely toxic. Handle this chemical only in an adequately ventilated hood with extreme caution.</td>
 </tr>
 <tr>
 <td>Trimethylsilyl triflate</td>
 <td>Alfa Aesar</td>
 <td>A12535</td>
 <td></td>
 </tr>
 <tr>
 <td>Sodium Azide</td>
 <td>Sigma-Aldrich</td>
 <td>S8032</td>
 <td>Shock sensitive.</td>
 </tr>
 <tr>
 <td>Tetrabutylammonium azide</td>
 <td>Aldrich</td>
 <td>651664</td>
 <td>If possible, store and handle in a glovebox due to this compound's hygroscopic nature.</td>
 </tr>
 <tr>
 <td>1-Heptyne</td>
 <td>Acros</td>
 <td>223460250</td>
 <td></td>
 </tr>
 <tr>
 <td>Styrene</td>
 <td>Aldrich</td>
 <td>240869</td>
 <td></td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>[header]</td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Material</td>
 </tr>
 <tr>
 <td>Rotary Evaporator (Hei-VAP)</td>
 <td>Heidolph</td>
 <td>517-61000-01-0</td>
 <td></td>
 </tr>
 <tr>
 <td>Glovebox</td>
 <td>MBRAUN</td>
 <td>UL-018</td>
 <td></td>
 </tr>
 </tbody>
</table>

synthesis of hypervalent iodonium alkynyl triflates for the application of generating cyanocarbenes

Os procedimentos descritos neste artigo envolve a síntese e o isolamento de hipervalentes iodónio alcinilo triflatos (HIATs) e as suas reacções subsequentes com azidas para formar intermediários cyanocarbene. A síntese de triflatos alquinila hipervalente iodónio pode ser fácil, mas as dificuldades decorrem de seu isolamento e reatividade. Em particular, a necessidade de usar a filtração sob atmosfera inerte a -45 ° C durante alguns HIATs requer cuidados especiais e equipamento. Uma vez isolados, os compostos podem ser armazenadas e usadas em reacções com azidas para formar intermediários cyanocarbene. A evidência para a geração cyanocarbene é mostrado por extrusão de diazoto visível, bem como a caracterização de produtos que ocorrem a partir de inserção de OH, complexação sulfóxido, e ciclopropanação. Uma reacção secundária de formação cyanocarbene é a geração de uma vinilideno-carbeno e são discutidas as condições para controlar este processo. Temtambém potencial para formar um alcenilo triflato hipervalente iodónio e os meios de separação e o controlo da sua geração são fornecidos. A reacção envolve a inserção de OH utilizando um HIAT, azida de sódio ou azida de tetrabutilamónio, e metanol como solvente / substrato. A reacção de complexação sulfóxido utiliza um HIAT, azida de sódio ou azida de tetrabutilamónio, e dimetil sulfóxido como solvente. Os cyclopropanations pode ser realizada com ou sem a utilização de solvente. A fonte de azida deve ser de azida de tetrabutilamónio e o substrato mostrado é estireno.

A figura 1 ilustra a síntese de um HIAT usando cyanophenyliodonium alcinilo triflato. O HIAT pode então ser utilizada para gerar cyanocarbenes que serão sujeitos a inserção de OH de ciclopropanação. A reacção de inserção de OH com Fenil HIAT produz 2-metoxi-2-fenilacetonitrilo na-se a um rendimento de 75%. A reacção de ciclopropanação com Fenil HIAT produz 1,2-diphenylcyclopropanecarbonitrile em até um rendimento de 61%. Embora não demonstrado no vídeo, dimetil sulfóxido complexação...

Watch this Scientific Journal Video about Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes at JoVE.com

Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes

Aqui descreve-se a síntese, isolamento, e as reacções de hipervalentes iodónio alcinilo triflatos (HIATs) com azidas de gerar cyanocarbenes. Os procedimentos envolvem técnicas de ar-sensíveis e cryogen, incluindo filtração a frio sob uma atmosfera inerte. Também serão discutidos Manuseio e segurança dos compostos sintetizados.

Síntese de hipervalente iodónio Alquinilo triflatos de Aplicação de Geração Cyanocarbenes

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent ...

synthesis-hypervalent-iodonium-alkynyl-triflates-for-application

Research

JoVE Journal

Chemistry

10.8K visualizações.  University of North Carolina at Greensboro.  Aqui descreve-se a síntese, isolamento, e as reacções de hipervalentes iodónio alcinilo triflatos (HIATs) com azidas de gerar cyanocarbenes. Os procedimentos envolvem técnicas de ar-sensíveis e cryogen, incluindo filtração a frio sob uma atmosfera inerte. Também serão discutidos Manuseio e segurança dos compostos sintetizados. 

Vídeo: Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes

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.

Síntese, Entrega Celular e<em&gt; In vivo</em&gt; Aplicação de sensores de pH à base de Dendrímero

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

Química

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 &#176;C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

Protocolo para a Síntese de Derivados de Anilina Orto-trifluorometoxilados

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

HKUST-1 as a Heterogeneous Catalyst for the Synthesis of Vanillin

Vanillin (4-hydoxy-3-methoxybenzaldehyde) is the main component of the extract of vanilla bean. The natural vanilla scent is a mixture of approximately 200 different odorant compounds in addition to vanillin. The natural extraction of vanillin (from the orchid Vanilla planifolia, Vanilla tahitiensis and Vanilla pompon) represents only 1% of the worldwide production and since this process is expensive and very long, the rest of the production of vanillin is synthesized. Many biotechnological approaches can be used for the synthesis of vanillin from lignin, phenolic stilbenes, isoeugenol, eugenol, guaicol, etc., with the disadvantage of harming the environment since these processes use strong oxidizing agents and toxic solvents. Thus, eco-friendly alternatives on the production of vanillin are very desirable and thus, under current investigation. Porous coordination polymers (PCPs) are a new class of highly crystalline materials that recently have been used for catalysis. HKUST-1 (Cu3(BTC)2(H2O)3, BTC = 1,3,5-benzene-tricarboxylate) is a very well known PCP which has been extensively studied as a heterogeneous catalyst. Here, we report a synthetic strategy for the production of vanillin by the oxidation of trans-ferulic acid using HKUST-1 as a catalyst.

The conversion of trans-ferulic acid to vanillin was achieved by heterogeneous catalysis. HKUST-1 was employed in this synthesis and the essential step in the catalytic process was the generation of unsaturated metal sites. Thus, when the catalyst was activated under vacuum, full vanillin conversion (yield of 95%) was obtained.

HKUST-1 como um catalisador heterogéneo para a Síntese de vanilina

Vanillin (4-hydoxy-3-methoxybenzaldehyde) is the main component of the extract of vanilla bean. The natural vanilla scent is a mixture of approximately ...

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.

Síntese de Bioconjugados de proteínas<em&gt; via</em&gt; Química cisteína-maleimida

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

Facile Synthesis of Worm-like Micelles by Visible Light Mediated Dispersion Polymerization Using Photoredox Catalyst

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins with the synthesis of a hydrophilic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) homopolymer using reversible addition-fragmentation chain-transfer (RAFT) polymerization. Under mild visible light irradiation (&#955; = 460 nm, 0.7 mW/cm2), this macro-chain transfer agent (macro-CTA) in the presence of a ruthenium based photoredox catalyst, Ru(bpy)3Cl2 can be chain extended with a second monomer to form a well-defined block copolymer in a process known as Photoinduced Electron Transfer RAFT (PET-RAFT). When PET-RAFT is used to chain extend POEGMA with benzyl methacrylate (BzMA) in ethanol (EtOH), polymeric nanoparticles with different morphologies are formed in situ according to a polymerization-induced self-assembly (PISA) mechanism. Self-assembly into nanoparticles presenting POEGMA chains at the corona and poly(benzyl methacrylate) (PBzMA) chains in the core occurs in situ due to the growing insolubility of the PBzMA block in ethanol. Interestingly, the formation of highly pure worm-like micelles can be readily monitored by observing the onset of a highly viscous gel in situ due to nanoparticle entanglements occurring during the polymerization. This process thereby allows for a more reproducible synthesis of worm-like micelles simply by monitoring the solution viscosity during the course of the polymerization. In addition, the light stimulus can be intermittently applied in an ON/OFF manner demonstrating temporal control over the nanoparticle morphology.

This article describes a process for producing polymeric self-assembled nanoparticles using visible light mediated dispersion polymerization. Using low energy visible light to control the polymerization allows for the reproducible formation of self-assembled worm-like micelles at high solids content.

Síntese Facile de micelas Worm-like por luz visível Mediated Dispersão Polimerização Usando Photoredox Catalisador

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins ...

Synthesis and Mass Spectrometry Analysis of Oligo-peptoids

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have been thought of as a type of molecular information storage. Mass spectrometry analysis has been considered the method of choice for sequencing peptoids. Peptoids can be synthesized via solid phase chemistry using a repeating two-step reaction cycle. Here we present a method to manually synthesize oligo-peptoids and to analyze the sequence of the peptoids using tandem mass spectrometry (MS/MS) techniques. The sample peptoid is a nonamer consisting of alternating N-(2-methyloxyethyl)glycine (Nme) and N-(2-phenylethyl)glycine (Npe), as well as an N-(2-aminoethyl)glycine (Nae) at the N-terminus. The sequence formula of the peptoid is Ac-Nae-(Npe-Nme)4-NH2, where Ac is the acetyl group. The synthesis takes place in a commercially available solid-phase reaction vessel. The rink amide resin is used as the solid support to yield the peptoid with an amide group at the C-terminus. The resulting peptoid product is subjected to sequence analysis using a triple-quadrupole mass spectrometer coupled to an electrospray ionization source. The MS/MS measurement produces a spectrum of fragment ions resulting from the dissociation of charged peptoid. The fragment ions are sorted out based on the values of their mass-to-charge ratio (m/z). The m/z values of the fragment ions are compared against the nominal masses of theoretically predicted fragment ions, according to the scheme of peptoid fragmentation. The analysis generates a fragmentation pattern of the charged peptoid. The fragmentation pattern is correlated to the monomer sequence of the neutral peptoid. In this regard, MS analysis reads out the sequence information of the peptoids.

A protocol is described for the manual synthesis of oligo-peptoids followed by sequence analysis by mass spectrometry.

Síntese e análise de espectrometria de massa de Oligo-peptoids

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have ...

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.

Síntese de nanofios de Au substrato ligados através de um mecanismo de crescimento ativo de superfície

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

Synthesis of Soft Polysiloxane-urea Elastomers for Intraocular Lens Application

This study discusses a synthesis route for soft polysiloxane-based urea (PSU) elastomers for their applications as accommodating intraocular lenses (a-IOLs). Aminopropyl-terminated polydimethylsiloxanes (PDMS) were previously prepared via the ring-chain equilibration of the cyclic siloxane octamethylcyclotetrasiloxane (D4) and 1,3-bis(3-aminopropyl)-tetramethyldisiloxane (APTMDS). Phenyl groups were introduced into the siloxane backbone via the copolymerization of D4 and 2,4,6,8-tetramethyl-2,4,6,8-tetraphenyl-cyclotetrasiloxane (D4Me,Ph). These polydimethyl-methyl-phenyl-siloxane-block copolymers were synthesized for increasing the refractive indices of polysiloxanes. For applications as an a-IOL, the refractive index of the polysiloxanes must be equivalent to that of a young human eye lens. The polysiloxane molecular weight is controlled by the ratio of the cyclic siloxane to the endblocker APTMDS. The transparency of the PSU elastomers is examined by the transmittance measurement of films between 200 and 750 nm, using a UV-Vis spectrophotometer. Transmittance values at 750 nm (upper end of the visible spectrum) are plotted against the PDMS molecular weight, and &#62; 90% of the transmittance is observed until a molecular weight of 18,000 g&#183;mol&#8722;1. Mechanical properties of the PSU elastomers are investigated using stress-strain tests on die-cut dog-bone-shaped specimens. For evaluating mechanical stability, mechanical hysteresis is measured by repeatedly stretching (10x) the specimens to 5% and 100% elongation. Hysteresis considerably decreases with the increase in the PDMS molecular weight. In vitro cytotoxicity of some selected PSU elastomers is evaluated using an MTS cell viability assay. The methods described herein permit the synthesis of a soft, transparent, and noncytotoxic PSU elastomer with a refractive index approximately equal to that of a young human eye lens.

This study describes synthetic routes for aminopropyl-terminated polydimethylsiloxanes and polydimethyl-methyl-phenyl-siloxane-block copolymers and for soft polysiloxane-based urea (PSU) elastomers. It presents the application of PSUs as accommodating an intraocular lens. An evaluation method for in vitro cytotoxicity is also described.

Síntese de elastômeros de silicone macio-ureia para aplicação de lente intra-ocular

This study discusses a synthesis route for soft polysiloxane-based urea (PSU) elastomers for their applications as accommodating intraocular lenses ...

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates

Maleimide-bearing bifunctional probes have been employed for decades for the site-selective modification of thiols in biomolecules, especially antibodies. Yet maleimide-based conjugates display limited stability in vivo because the succinimidyl thioether linkage can undergo a retro-Michael reaction. This, of course, can lead to the release of the radioactive payload or its exchange with thiol-bearing biomolecules in circulation. Both of these processes can produce elevated activity concentrations in healthy organs as well as decreased activity concentrations in target tissues, resulting in reduced imaging contrast and lower therapeutic ratios. In 2018, we reported the creation of a modular, stable, and easily accessible phenyloxadiazolyl methyl sulfone reagent &#8212; dubbed &#8216;PODS&#8217; &#8212; as a platform for thiol-based bioconjugations. We have clearly demonstrated that PODS-based site-selective bioconjugations reproducibly and robustly create homogenous, well-defined, highly immunoreactive, and highly stable radioimmunoconjugates. Furthermore, preclinical experiments in murine models of colorectal cancer have shown that these site-selectively labeled radioimmunoconjugates exhibit far superior in vivo performance compared to radiolabeled antibodies synthesized via maleimide-based conjugations. In this protocol, we will describe the four-step synthesis of PODS, the creation of a bifunctional PODS-bearing variant of the ubiquitous chelator DOTA (PODS-DOTA), and the conjugation of PODS-DOTA to the HER2-targeting antibody trastuzumab.

In this protocol, we will describe the synthesis of PODS, a phenyoxadiazolyl methyl sulfone-based reagent for the site-selective attachment of cargos to the thiols of biomolecules, particularly antibodies. In addition, we will describe the synthesis and characterization of a PODS-bearing bifunctional chelator and its conjugation to a model antibody.

Síntese e Bioconjugation dos reagentes Thiol-reativa para a criação de Site-seletivamente modificado Immunoconjugates

Maleimide-bearing bifunctional probes have been employed for decades for the site-selective modification of thiols in biomolecules, especially antibodies. ...

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the preparation of all-carbon quaternary centers. Though conjugate additions of organometallic reagents are typically performed utilizing highly reactive organolithium or Grignard reagents, organozinc reagents have garnered attention for their enhanced chemoselectivity and mild reactivity. Despite numerous recent advances with more reactive diorganozinc and mixed diorganozinc reagents, the generation of all-carbon quaternary centers via the conjugate addition of functionalized monoorganozinc reagents remains a challenge. This protocol details a convenient and mild &#8220;one-pot&#8221; preparation and copper mediated conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to afford a broad scope of all-carbon quaternary centers in generally excellent yield and diastereoselectivity. Key to the development of this technology is the utilization of DMA as a reaction solvent with TMSCl as a Lewis acid. Notable advantages to this methodology include the operational simplicity of the organozinc reagent preparation afforded by the utilization of DMA as a solvent, as well as an efficient conjugate addition mediated by various Cu(I) and Cu(II) salts. Moreover, an intermediate silyl enol ether can be isolated utilizing a modified workup procedure. The substrate scope is limited to cyclic unsaturated ketones, and the conjugate addition is impeded by stabilized (e.g., allyl, enolate, homoenolate) and sterically encumbered (e.g., neopentyl, o-aryl) monoorganozinc reagents. Conjugate additions to five- and seven-membered rings were effective, albeit in lower yields compared with six-membered ring substrates.

A simple and practical protocol for the efficient conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to furnish all-carbon quaternary centers was developed.

Síntese eficiente de todos os centros quaternários de carbono através da adição conjugada de brometos Monoorganozinc funcionalizados

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the ...