Name: preparation of a corannulene-functionalized hexahelicene by copper(i)-catalyzed alkyne-azide cycloaddition of nonplanar polyaromatic units
Uploaded: 2016-09-18T14:00:00.000+00:00
Duration: 9 min 35 s
Description: Watch this Scientific Journal Video about Preparation of a Corannulene-functionalized Hexahelicene by CopperI-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units at JoVE.com

This work was funded by the Spanish Ministerio de Econom&#236;a y Competitividad (CTQ 2013-41067-P). H.B. acknowledge with thanks a MEC-FPI grant.

1. Funcionalización de 2,15-Dimethylhexahelicene <ol><li> Dibromación de 2,15-dimethylhexahelicene <ol><li> Pesar 0,356 g (1,0 mmol) de 2,15-dimethylhexahelicene, 0,374 g (2,1 mmol) de bromosuccinimida recién recristalizado N (NBS) y 24 mg (0,07 mmol) de peróxido de benzoilo (BPO) (70% en peso con 30% de agua como estabilizador). Coloque todos los sólidos en un matraz de Schlenk de 100 ml con una barra de agitación magnética. Puesto bajo atmósfera de nitrógeno mediante tres ciclos de evacuación de gases, seguido por el rellenado de gas inerte en la línea de Schlenk. </li><li> Añadir 21 ml de tetracloruro de carbono (CCl 4). Desgasificar la solución por el mismo evacuación / proceso de recarga (etapa 1.1.1) con agitación vigorosa y con cuidado a fin de evitar la pérdida masiva de disolvente. </li><li> Se calienta a reflujo (77 ° C) la mezcla con un baño de aceite durante 4 horas. Comprobar la reacción mediante resonancia magnética nuclear de 1H (RMN). Dobletes entre 3,7 ppm y 4,0 ppm shoparece ULD. Ellos indican la presencia de -CH diastereotópicos 2 - grupos (Figura 1). </li><li> Una vez terminado, se enfría la mezcla a temperatura ambiente y eliminar el disolvente bajo vacío. Configurar una trampa llena de nitrógeno líquido para evitar la contaminación de la bomba. </li><li> Se vuelve a disolver el crudo en 30 ml de diclorometano (DCM), transferir a un matraz de fondo redondo y se mezcla con 4 g de gel de sílice (típicamente agregar 5 veces el peso bruto). Se concentra la mezcla en un evaporador rotatorio. </li><li> Mientras tanto, llenar una columna (longitud de alrededor de 20 cm y un espesor de 4,5 cm) con SiO 2 gel mezclado previamente con hexano / acetato de etilo (95: 5) como fase móvil. Añadir la mezcla a la parte superior de la columna y a continuación, añadir una capa de arena (2 cm). </li><li> Con cuidado, vierta en la nueva fase móvil y llevar a cabo la cromatografía mediante la recopilación de las fracciones en tubos de ensayo (típicamente 20 ml por tubo y cerca de 4 ml de la elución producto esperado). Compruebe fracciones por cromatografía en capa fina(TLC) con la misma fase móvil (hexano / acetato de etilo 95: 5) y la imagen bajo luz UV. El producto esperado (4b) debe eluir con un factor de retención (Rf) de 0,35 como un aceite amarillo después de combinar todos querían fracciones y la eliminación del disolvente en el evaporador rotativo. se deben obtener 334 mg (rendimiento 65%). NOTA: Todas las técnicas de Schlenk, el uso de un baño de aceite para la configuración de cromatografía de calefacción y de columna será ampliamente utilizados en la mayoría de los protocolos, por lo que de ahora en adelante, no se trata en detalle y sólo unos pocos comentarios, cuando sea necesario, ser dado. </li></ol></li></ol><img alt="Figura 1" src="/files/ftp_upload/53954/53954fig1.jpg" /> . Figura 1 1 H-NMR espectros (500 MHz, CDCl3) de 2,15 -dimethylhelicene (arriba) y una alícuota tomada después de 2 horas Nuevas señales, que corresponde a -CH 2 -.., se representan en un círculo rojo (inferior) <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53954/53954fig1large.jpg" target="_blank">Haga clic aquí para ver una versión más grande de esta figura.</a> <ol start="2"><li> Síntesis de 2,15-bis (azidometil) hexaheliceno <ol><li> Pesar 0,103 g (0,2 mmol) de 2,15-bis (bromometil) hexaheliceno y 0,390 g (6 mmol) de azida de sodio. Coloque ambos sólidos en un matraz Schlenk de 50 ml equipado con una barra magnética y poner bajo una atmósfera de nitrógeno. </li><li> Mezclar 8,6 ml de tetrahidrofurano (THF) con 5,2 ml de agua (H 2 O) y verter la mezcla de disolventes en el matraz de Schlenk. Desgasificar la solución. </li><li> Se calienta a reflujo (65 ° C) durante 3 horas. Compruebe la reacción por 1H-RMN. CH2 - señales deben desplazar a 3,75 ppm (Figura 2). </li><li> Posteriormente, cool por la mezcla a temperatura ambiente y eliminar el THF bajo vacío. Se diluye con 50 ml de H 2 O. </li><li> Transferir la mezcla a un embudo de separación y se extrajo tres veces con 40 ml de DCM. Combinar todas las fases orgánicas y se lava con pura H2O (50 ml). </li><li> Se purificó el crudo por cromatografía en columna sobre gel de sílice utilizando hexano / acetato de etilo (85:15) como fase móvil para dar un aceite de color amarillo a Rf = 0,38 que corresponde a hexaheliceno 2,15-bis (azomethyl) (5b). se deben obtener 70 mg (rendimiento 80%). </li></ol></li></ol><img alt="Figura 2" src="/files/ftp_upload/53954/53954fig2.jpg" /> Figura 2: 1H-NMR espectros (500 MHz, CDCl3) del 4 b (parte superior) y una alícuota tomada después de 3 horas(parte inferior). Tenga en cuenta los cambios en la región alifática. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53954/53954fig2large.jpg" target="_blank">Haga clic aquí para ver una versión más grande de esta figura.</a> 2. Funcionalización de Corannulene <ol><li> Monobromación de Corannulene <ol><li> Pesar 0,125 g (0,5 mmol) de corannulene, 89 mg (0,5 mmol) de NBS recién recristalizado y 17 mg de oro (III) hidrato de cloruro. </li><li> Coloque todos los compuestos en un vial de 10 ml diseñados especialmente para las reacciones de microondas provisto de una barra magnética y luego se ponen en una atmósfera de nitrógeno con la ayuda de un matraz de fondo redondo de 2 cuellos. </li><li> Añadir 7 ml de 1,2-dicloroetano (DCE) y desgasificar la solución. </li><li> Sonicar la mezcla durante 2 min para dispersar partículas de sal de oro. </li><li> El calor en el interior del reactor de microondas a 100 ° C durante 2 hr. </li><li> Cuando haya terminado, transferir el crudo a un matraz de fondo redondo y eliminar el disolvente por rotary evaporación. </li><li> Se purificó el crudo por cromatografía en columna sobre SiO2 gel usando hexano como fase móvil. NOTA: Bromocorannulene (4a) se obtiene como un sólido de color amarillo a Rf = 0,38. se deben obtener 99 mg (rendimiento 60%). Corannulene sin reaccionar (3a) se puede recuperar y se almacena para usos adicionales. Parece a Rf = 0,29. </li></ol></li><li> El acoplamiento de Sonogashira Bomocorannulene y etiniltrimetilsilano <ol><li> Pesar 49 mg (0,15 mmol) de bromocorannulene, 11 mg (0,015 mmol) de [PdCl 2 (dppf)] 49,50 (dppf ser 1,1-&#39;bis (diphenylphsphino) ferroceno, 3 mg (0,015 mmol) de CuI. 51 </li><li> Coloque todos los sólidos en un matraz de Schlenk de 50 ml junto con una barra magnética y poner bajo una atmósfera de nitrógeno. </li><li> Añadir 5,0 ml de trietilamina (NEt 3) y desgasificar la mezcla. </li><li> Por último, añadir 104 l (0,75 mmol) de etiniltrimetilsilano. </li><li> Sonicar la mezcla durante 2 min adispersar partículas de sal de metal. </li><li> Se calienta a 85 ° C durante 24 hr con sonicación periódica para prevenir la deposición de sales metálicas. NOTA: El color de la mezcla se volvió a negro pronto, lo que indica la presencia de paladio (0). </li><li> Enfriar a temperatura ambiente y se evapora NEt 3 al vacío. </li><li> Se vuelve a disolver en 20 ml de DCM y se purifica por cromatografía en columna sobre gel de sílice eluyendo con hexano para dar un sólido de color amarillo a Rf = 0,28 que corresponde a 5a. se deben obtener 41 mg (rendimiento 78%). NOTA: Si el crudo se filtra a través de una almohadilla de Celite en DCM, se podría obtener una muestra pura razonable, sin embargo los derivados de fosfina no se eliminan totalmente. </li></ol></li><li> Preparación de Ethynylcorannulene por desprotección TMS <ol><li> Pesar 35 mg (0,10 mmol) de 5a y 7,3 mg (0,125 mmol) de fluoruro de potasio anhidro. </li><li> Colocar todos los sólidos en un 50 ml matraz Schlenk equipado con una barra magnética de unad poner bajo atmósfera de nitrógeno. </li><li> Mezclar 4 ml de THF y 4 ml de metanol (MeOH) y se vierte la mezcla en el matraz de Schlenk. Degas a fondo. </li><li> Dejar en reposo a temperatura ambiente, Mantener el matraz protegido de la luz cubriéndola con una película opaca. Compruebe la reacción por 1H-RMN examinado 3,48 ppm. Una señal que corresponde a -CCH debe surgir (Figura 3). NOTA: A pesar de que este compuesto tiene un alquino terminal que es reactivo y se descompone fácilmente, no se encontraron problemas durante el trabajo arriba descrito a continuación. Se llevó a cabo bajo la luz natural. </li><li> Una vez terminado, retirar el THF al vacío y se diluye con 10 ml de agua, transferir todo a un embudo de separación. </li><li> Se extrae con DCM (3 x 15 ml), se combinan todas las fases orgánicas en un matraz de fondo redondo y se concentra en un evaporador rotatorio a temperatura ambiente para obtener finalmente un sólido amarillo correspondiente a 6a. 27 mg deben obtenerse (rendimiento cuantitativo). </li></ol></li></ol><img alt="figura 3" src="/files/ftp_upload/53954/53954fig3.jpg" /> Figura 3:.. 1 H-NMR espectros (500 MHz, CDCl3) del 5 al (arriba) y 6 bis (parte inferior) singlete -CCH se representa en un círculo rojo <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53954/53954fig3large.jpg" target="_blank">Haga clic aquí para ver una versión más grande de esta figura.</a> 3. Montaje Final por Click Química <ol><li> Pesar 15,3 mg (0,035 mmol) de 5B, 20,0 mg (0,073 mmol) de 6a, 1,4 mg (0,007 mmol) de sal sódica de ácido ascórbico, 1,7 mg (0,007 mmol) de CuSO 4 · 5H 2 O. </li><li> Coloque todos los sólidos en un matraz Schlenk de 50 ml equipado con amagnetic barra y poner bajo una atmósfera de nitrógeno. </li><li> Mezclar 3 ml de H2O y 12 ml de THF y se vierte la mezcla en el matraz de Schlenk. Desgasificar la solución a fondo. </li><li> Se calienta a 65 ° C durante 3 días con un condensador conectado a la parte superior del matraz y comprobar periódicamente la reacción para controlar la temperatura, la agitación y el volumen de disolvente. Compruebe la reacción por 1H-RMN. La señal en 3,48 ppm debe desaparecer y ser desplazado a 7,27 ppm que indica el consumo de corannulene etinilo y la existencia de la unidad de triazol (Figura 4). </li><li> Cuando haya terminado, eliminar el THF bajo vacío y se diluye con 20 ml de agua, la transferencia de la mezcla a un embudo de separación. </li><li> Se extrae con DCM (3 x 20 ml), se combinan todas las fases orgánicas en un matraz de fondo redondo y se concentra en un evaporador rotatorio. </li><li> Se purificó el crudo por cromatografía en columna sobre SiO2 gel eluyendo con hexano / acetato de etilo (1: 1) para dar un sólido de color amarillo pálido a Rf = 0,59correspondiente a 7. se deben obtener 27 mg (rendimiento 75%). </li></ol><img alt="Figura 4" src="/files/ftp_upload/53954/53954fig4.jpg" /> Figura 4: 1H-NMR espectros (500 MHz, CDCl3) del 5 b (parte superior), 6 bis (medio) y una alícuota tomada después de 2 días (abajo) Tenga en cuenta la desaparición de la señal -CCH en el crudo.. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53954/53954fig4large.jpg" target="_blank">Por favor, clic aquí para ver una versión más grande de esta figura.</a>

The authors have nothing to disclose.

El compuesto final 7 se ha preparado después de 6 pasos de precursores aromáticos policíclicos no planas 3 y 3b con moderada a muy buenos rendimientos en cada reacción. La principal limitación observada en esta ruta fue la bromación de ambos compuestos poliaromáticos no planas. Sin embargo, en el caso del compuesto 4 a, una cantidad importante de corannulene libre se puede recuperar para otros us...

Debido a su geometría especial, corannulene y helicenes son moléculas que pueden adoptar una estructura lejos de planaridad y dan lugar a propiedades interesantes. 1-15 En los últimos años, la búsqueda de los receptores moleculares de los nanotubos de carbono y fulerenos es un área muy activa 16-19, debido, principalmente, a sus potenciales aplicaciones como materiales para células solares orgánicas, transistores, sensores y otros dispositivos. 20-28 la excelente complementariedad de forma entre corannulene y un fullereno han atraído la atención de varios investigadores con el objetivo de diseñar receptores moleculares capaces de establecer la asociación supramolecular por las fuerzas de dispersión. 29-39 La química de los compuestos poliaromáticos no planas mencionadas anteriormente es similar al descrito para las moléculas totalmente planas, pero a veces es difícil encontrar condiciones adecuadas para alcanzar selectividades y rendimientos deseados. 40 </sup&gt; En este trabajo se presenta la síntesis de una molécula (7) que tiene tres unidades poliaromáticos en algunos pasos con buenos rendimientos mediante la aplicación de técnicas sencillas y típicas que se encuentran en todos los laboratorios de investigación. La molécula es de gran importancia, ya que puede adoptar una conformación de pinza para establecer buenas interacciones con C 60 37 en la solución; y puede abrir una línea de investigación como un receptor potencial para altos fullerenos quirales gracias al enlazador heliceno, que es una molécula quiral debido a la existencia de un eje estereogénico. 41-45 Sin embargo, sólo heliceno racémica se utilizará en este trabajo. En este punto, la única limitación para sintetizar estos receptores es la preparación de helicenes y corannulenes, ya que no están disponibles comercialmente. Pero, de acuerdo con los nuevos métodos publicados en otro lugar 46 a 48 se pueden obtener en cantidades adecuadas en un corto período de tiempo razonable.

<table><tbody><tr><td>2,15-Dimethylhexahelicene</td><td>N/A</td><td>N/A</td><td>Prepared according to reference 5b,c in the main text.</td></tr><tr><td>Corannulene</td><td>N/A</td><td>N/A</td><td>Prepared according to reference 5a in the main text.</td></tr><tr><td>&lt;em&gt;N&lt;/em&gt;-Bromosuccinimide (NBS)</td><td>Sigma Aldrich</td><td>B8.125-5</td><td>ReagentPlus&amp;reg;, 99%. Recrystallized from hot water.</td></tr><tr><td>Benzoyl peroxide (BPO)</td><td>Sigma Aldrich</td><td>B-2030</td><td>~70% (titration). 30% water as stabilizer.</td></tr><tr><td>Sodium azide</td><td>Sigma Aldrich</td><td>S2002</td><td>ReagentPlus&amp;reg;, &amp;ge;99.5%.</td></tr><tr><td>Gold(III) chloride Hydrate</td><td>Sigma Aldrich</td><td>50778</td><td>puriss. p.a., ACS reagent, &amp;ge;49% Au basis.</td></tr><tr><td>Ethynyltrimethylsilane</td><td>Sigma Aldrich</td><td>218170</td><td>98%</td></tr><tr><td>[PdCl&lt;sub&gt;2&lt;/sub&gt;(dppf)]</td><td>N/A</td><td>N/A</td><td>Prepared according to reference 6 in the main text.</td></tr><tr><td>CuI</td><td>N/A</td><td>N/A</td><td>Prepared according to reference 7 in the main text.</td></tr><tr><td>KF</td><td>Sigma Aldrich</td><td>307599</td><td>99%, spray-dried.</td></tr><tr><td>(+)-Sodium L-ascorbate</td><td>Fluka</td><td>11140</td><td>BioXtra, &amp;ge;99.0% (NT).</td></tr><tr><td>Copper(II) Sulphate 5-hydrate</td><td>Panreac</td><td>131270</td><td>For analysis.</td></tr><tr><td>Carbon tetrachloride (CCl&lt;sub&gt;4&lt;/sub&gt;)</td><td>Fluka</td><td>87030</td><td>For IR spectroscopy, &amp;ge;99.9%.</td></tr><tr><td>Dichloromethane (DCM)</td><td>Fisher Scientific</td><td>D/1852/25</td><td>Analytical reagent grade. Distilled prior to use.</td></tr><tr><td>Hexane</td><td>Fisher Scientific</td><td>H/0355/25</td><td>Analytical reagent grade. Distilled prior to use.</td></tr><tr><td>Ethyl acetate</td><td>Scharlau</td><td>AC0145025S</td><td>Reagent grade. Distilled prior to use.</td></tr><tr><td>Tetrahydrofuran (THF)</td><td>Fisher Scientific</td><td>T/0701/25</td><td>Analytical reagent grade. Distilled prior to use.</td></tr><tr><td>1,2-Dichloroethane (DCE)</td><td>Sigma Aldrich</td><td>D6,156-3</td><td>ReagentPlus&amp;reg;, 99%.</td></tr><tr><td>Methanol (MeOH)</td><td>VWR</td><td>20847.36</td><td>AnalaR NORMAPUR.</td></tr><tr><td>Triethyl amine (NEt&lt;sub&gt;3&lt;/sub&gt;)</td><td>Sigma Aldrich</td><td>T0886</td><td>&amp;ge;99%</td></tr><tr><td>Silica gel</td><td>Acros</td><td>360050010</td><td>Particle size 40-60 mm.</td></tr><tr><td>Sand - low iron</td><td>Fisher Scientific</td><td>S/0360/63</td><td>General purpose grade.</td></tr><tr><td>TLC Silica gel 60 F&lt;sub&gt;254&lt;/sub&gt;</td><td>Merck</td><td>1.05554.0001</td><td></td></tr><tr><td>Monowave 300 (Microwave reactor)</td><td>Anton Para</td><td></td><td></td></tr><tr><td>Sonicator</td><td>Grupo Selecta</td><td>3000513</td><td>6 Litres.</td></tr></tbody></table>

preparation of a corannulene-functionalized hexahelicene by copper(i)-catalyzed alkyne-azide cycloaddition of nonplanar polyaromatic units

The main purpose of this video is to show 6 reaction steps of a convergent synthesis and prepare a complex molecule containing up to three nonplanar polyaromatic units, which are two corannulene moieties and a racemic hexahelicene linking them. The compound described in this work is a good host for fullerenes. Several common organic reactions, such as free-radical reactions, C-C coupling or click chemistry, are employed demonstrating the versatility of functionalization that this compound can accept. All of these reactions work for planar aromatic molecules. With subtle modifications, it is possible to achieve similar results for nonplanar polyaromatic compounds.

Corannulene (3 a) y 2,15-dimethylhexahelicene (3 b) se pueden preparar siguiendo los métodos actuales 46-48 de una manera sencilla con muy buenos rendimientos (Figura 5). Ambos comparten una molécula común, 2,7-dimetilnaftaleno, como material de partida, dando lugar a una divergente a la síntesis convergente de la molécula final. <p class="jove_content" fo:keep-together.within-page="a...

Watch this Scientific Journal Video about Preparation of a Corannulene-functionalized Hexahelicene by CopperI-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units at JoVE.com

Preparation of a Corannulene-functionalized Hexahelicene by CopperI-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

A continuación, se presenta un protocolo para sintetizar un compuesto orgánico complejo compuesto por tres unidades poliaromáticos no planas, montado fácilmente con rendimientos razonables.

Preparación de un hexaheliceno funcionalizado-Corannulene por cobre (I) catalizada cicloadición Alquino-azida de Unidades no planas poliaromáticos

The main purpose of this video is to show 6 reaction steps of a convergent synthesis and prepare a complex molecule containing up to three nonplanar ...

preparation-corannulene-functionalized-hexahelicene-copper-i

Universidad San Sebastian

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Organic Chemistry

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Unit 1

Preparation of a Corannulene-functionalized Hexahelicene by Copper(I)-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

Aromatic Compounds

SCIENTISTS IN ACTION

11.4K vistas.  Universidad de Valladolid.  A continuación, se presenta un protocolo para sintetizar un compuesto orgánico complejo compuesto por tres unidades poliaromáticos no planas, montado fácilmente con rendimientos razonables. 

Video: Preparation of a Corannulene-functionalized Hexahelicene by CopperI-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

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

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent reactions with azides to form cyanocarbene intermediates. The synthesis of hypervalent iodonium alkynyl triflates can be facile, but difficulties stem from their isolation and reactivity. In particular, the necessity to use filtration under inert atmosphere at -45 &deg;C for some HIATs requires special care and equipment. Once isolated, the compounds can be stored and used in reactions with azides to form cyanocarbene intermediates. 
The evidence for cyanocarbene generation is shown by visible extrusion of dinitrogen as well as the characterization of products that occur from O-H insertion, sulfoxide complexation, and cyclopropanation. A side reaction of the cyanocarbene formation is the generation of a vinylidene-carbene and the conditions to control this process are discussed. There is also potential to form a hypervalent iodonium alkenyl triflate and the means of isolation and control of its generation are provided. The O-H insertion reaction involves using a HIAT, sodium azide or tetrabutylammonium azide, and methanol as solvent/substrate. The sulfoxide complexation reaction uses a HIAT, sodium azide or tetrabutylammonium azide, and dimethyl sulfoxide as solvent. The cyclopropanations can be performed with or without the use of solvent. The azide source must be tetrabutylammonium azide and the substrate shown is styrene.

Herein is described the synthesis, isolation, and reactions of hypervalent iodonium alkynyl triflates (HIATs) with azides to generate cyanocarbenes. The procedures will involve air-sensitive and cryogen techniques, including cold filtration under an inert atmosphere. Handling and safety of the synthesized compounds will also be discussed.

Síntesis de hipervalente iodonio Alquinilo triflatos para la Aplicación de Generación Cyanocarbenes

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

Investigación

Química

Accessing Valuable Ligand Supports for Transition Metals: A Modified, Intermediate Scale Preparation of 1,2,3,4,5-Pentamethylcyclopentadiene

A reliable, intermediate scale preparation of 1,2,3,4,5-pentamethylcyclopentadiene (Cp*H) is presented, based on modifications of existing protocols that derive from initial 2-bromo-2-butene lithiation followed by acid mediated dienol cyclization. The revised synthesis and purification of the ligand avoids the use of mechanical stirring while still permitting access to significant quantities (39 g) of Cp*H in good yield (58%). The procedure offers other additional benefits, including a more controlled quench of excess lithium during the production of the intermediate heptadienols and a simplified isolation of Cp*H of sufficient purity for metallation with transition metals. The ligand was subsequently used to synthesize [Cp*MCl2]2 complexes of both iridium and ruthenium to demonstrate the utility of the Cp*H prepared and purified by our method. The procedure outlined herein affords substantial quantities of a ubiquitous ancillary ligand support used in organometallic chemistry while minimizing the need for specialized laboratory equipment, thus providing a simpler and more accessible entry point into the chemistry of 1,2,3,4,5-pentamethylcyclopentadiene.

Reliable, intermediate scale preparation of 1,2,3,4,5-pentamethylcyclopentadiene (Cp*H) is presented. The revised protocol for the synthesis and purification of the ligand minimizes the need for specialized laboratory equipment while simplifying reaction workups and product purification. Use of Cp*H in the synthesis of [Cp*MCl2]2 complexes (M = Ru, Ir) is also described.

El acceso a valiosa ligando Soportes para metales de transición: Una modificación, escala intermedia Preparación de 1,2,3,4,5-pentametilciclopentadieno

A reliable, intermediate scale preparation of 1,2,3,4,5-pentamethylcyclopentadiene (Cp*H) is presented, based on modifications of existing protocols that ...

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the aziridine ring. The utility of bicyclic aziridinium ions, specifically 1-azoniabicyclo[3.1.0]hexane and 1-azoniabicyclo[4.1.0]heptane tosylate highlighted in the aziridine ring openings by the nucleophile with the release of the ring strain to yield the corresponding ring-expanded azaheterocycles such as pyrrolidine, piperidine and azepane with diverse substituents on the ring in regio- and stereospecific manner. Herein, we report a simple and convenient method for the preparation of the stable 1-azabicyclo[4.1.0]heptane tosylate followed by selective ring opening via a nucleophilic attack either at the bridge or at the bridgehead carbon to yield piperidine and azepane rings, respectively. This synthetic strategy allowed us to prepare biologically active natural products containing piperidine and azepane motif including sedamine, allosedamine, fagomine and balanol in highly efficient manner.

Bicyclic aziridinium ions such as 1-azoniabicyclo[4.1.0]heptane tosylate were generated from 2-[4-tolenesulfonyloxybutyl]aziridine, which was utilized for the preparation of substituted piperidines and azepanes via regio- and stereospecific ring-expansion with various nucleophiles. This highly efficient protocol allowed us to prepare diverse azaheterocycles including natural products such as fagomine, febrifugine analogue and balanol.

Preparación de iones Aziridinium bicíclica estable y su apertura para la síntesis de Azaheterocycles

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the ...

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and 1-methyl-4-(1,2,2-triiodovinyl)benzene as representative examples for the practical chemoselective preparation of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes from the chemoselective iodination of terminal alkynes mediated by hypervalent-iodine reagents. The chemoselectivity was confirmed by using p-tolylethyne as a model substrate to screen a variety of iodine sources and/or the hypervalent-iodine reagents. A combination of tetrabutylammonium iodide (TBAI) and (diacetoxyiodo)benzene (PIDA) selectively generates 1-iodoalkynes, while a combination of KI and PIDA generates 1,2-diiodoalkenes. A one-pot synthesis based on both TBAI-PIDA and KI-PIDA yields the corresponding 1,1,2-triiodoalkenes. These protocols were subsequently applied to the synthesis of synthetically important aromatic and aliphatic 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes, which were obtained in good yield with excellent chemoselectivity.

Herein, detailed protocols for the oxidative iodination of terminal alkynes using hypervalent-iodine reagents are presented, which chemoselectively afford 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes.

Preparación estereoselectiva de 1 Iodoalkynes, 1, 2-Diiodoalkenes y 1.1.2-Triiodoalkenes basado en la yodación oxidativa de alquinos terminales

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and ...

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals

Protocols for the isolation of the commonly employed cyclic (alkyl)(amino) carbene (CAAC) and N-heterocyclic carbene (NHC) are reported. Furthermore, the synthesis of their mixed CAAC&#8211;NHC &#8220;Wanzlick&#8221; dimer and the synthesis of the related stable organic &#8220;olefin&#8221; radical are presented. The main goal of this manuscript is to give a detailed and general protocol for the synthetic chemist of any skill level on how to prepare free heterocyclic carbenes by deprotonation using filter cannulas. Due to the air-sensitivity of the synthesized compounds, all experiments are performed under inert atmosphere using either Schlenk technique or a dinitrogen filled glovebox. Controlling Wanzlick&#8217;s equilibrium (i.e., the dimerization of free carbenes), is a crucial requirement for the application of free carbenes in coordination chemistry or organic synthesis. Thus, we elaborate on the specific electronic and steric requirements favoring the formation of dimers, heterodimers, or monomers. We will show how proton catalysis allows for the formation of dimers, and how the electronic structure of carbenes and their dimers affects the reactivity with either moisture or air. The structural identity of the reported compounds is discussed based on their NMR spectra.

We present protocols for the isolation of stable heterocyclic carbenes. The synthesis of a cyclic (alkyl)(amino) carbene (CAAC) and an N-heterocyclic carbene (NHC) is demonstrated using filter cannulas and Schlenk technique. We furthermore present the synthesis of the related oxygen-sensitive, electron-rich mixed &#8220;Wanzlick dimer&#8221; and the reduced stable organic radical.

Aislamiento de carbenos libre mixto dímeros y sus radicales orgánicos

Protocols for the isolation of the commonly employed cyclic (alkyl)(amino) carbene (CAAC) and N-heterocyclic carbene (NHC) are reported. Furthermore, the ...

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.

Síntesis eficiente de los centros cuaternarios de carbono a través de la adición conjugada de bromuros 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 ...

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions

Aziridines, a class of reactive organic molecules containing a three-membered ring, are important synthons for the synthesis of a large variety of functionalized nitrogen-containing target compounds through the regiocontrolled ring-opening of C-substituted aziridines. Despite the tremendous progress in aziridine synthesis over the past decade, accessing contiguous bisaziridines efficiently remains difficult. Therefore, we were interested in synthesizing contiguous bisaziridines bearing an electronically diverse set of N-substituents beyond the single aziridine backbone for regioselective ring-opening reactions with diverse nucleophiles. In this study, chiral contiguous bisaziridines were prepared by organocatalytic asymmetric aziridination of chiral (E)-3-((S)-1-((R)-1-phenylethyl)aziridin-2-yl)acrylaldehyde with N-Ts-O-tosyl or N-Boc-O-tosyl hydroxylamine as the nitrogen source in the presence of (2S)-[diphenyl(trimethylsilyloxy)methyl]pyrrolidine as a chiral organocatalyst. Also demonstrated here are representative examples of regioselective ring-opening reactions of contiguous bisaziridines with a variety of nucleophiles such as sulfur, nitrogen, carbon, and oxygen, and the application of contiguous bisaziridines to the synthesis of multi-substituted chiral pyrrolidines by Pd-catalyzed hydrogenation.

Contiguous bisaziridines containing non-activated and activated aziridines were synthesized by asymmetric organocatalytic aziridinations and then subjected to chemoselective ring-opening reactions under acidic or basic conditions. The non-activated aziridine ring opens with less reactive nucleophiles under acidic conditions, whereas the activated aziridine ring opens with more reactive nucleophiles under basic conditions.

Preparación de bisaziridinas contiguas para reacciones regioselectivas de apertura de anillo

Aziridines, a class of reactive organic molecules containing a three-membered ring, are important synthons for the synthesis of a large variety of ...

Synthesis of a Borylated Ibuprofen Derivative Through Suzuki Cross-Coupling and Alkene Boracarboxylation Reactions

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drugs used to manage and treat pain and inflammation. In 2016, a new class of boron functionalized NSAIDs (bora-NSAIDs) was synthesized under mild conditions via the copper-catalyzed regioselective boracarboxylation of vinyl arenes using carbon dioxide (CO2 balloon) and a diboron reductant at room temperature. This original method was performed primarily in a glovebox or with a vacuum gas manifold (Schlenk line) under rigorous air-free and moisture-free conditions, which often led to irreproducible reaction outcomes due to trace impurities. The present protocol describes a simpler and more convenient benchtop method for synthesizing a representative bora-NSAID, bora-ibuprofen. A Suzuki-Miyaura cross-coupling reaction between 1-bromo-4-isobutylbenzene and vinylboronic acid pinacol ester produces 4-isobutylstyrene. The styrene is subsequently boracarboxylated regioselectively to provide bora-ibuprofen, an &#945;-aryl-&#946;-boryl-propionic acid, with good yield on a multi-gram scale. This procedure allows for the broader utilization of copper-catalyzed boracarboxylation in synthetic laboratories, enabling further research on bora-NSAIDs and other unique boron-functionalized drug-like molecules.

The present protocol describes a detailed benchtop catalytic method that yields a unique borylated derivative of ibuprofen.&#160;

Síntesis de un derivado del ibuprofeno borilado a través del acoplamiento cruzado de Suzuki y reacciones de boracarboxilación de alquenos

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drugs used to manage and treat pain and inflammation. In 2016, a new class of ...

Preparation of Alkynes: Alkylation Reaction

<h4>Introduction</h4>
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
<img alt="Figure1" src="/files/ftp_upload/11834/11834_PT_Figure_1.svg" style="text-align: center; height: 50px;" />
The reaction takes place in two steps:
1. The first step is the deprotonation of the terminal alkyne by the strong base forming an acetylide ion.
<img alt="Figure2" src="/files/ftp_upload/11834/11834_PT_Figure_2.svg" style="text-align: center; height: 50px;" />
2. The second step is a nucleophilic substitution reaction in which the acetylide ion reacts with the alkyl halide to form a new C&#8211;C bond.
<img alt="Figure3" src="/files/ftp_upload/11834/11834_PT_Figure_3.svg" style="text-align: center; height: 50px;" />
<h4>Reaction Mechanism &#8212;SN2 pathway </h4>
Acetylide ions are strong bases and can also function as good nucleophiles. The substitution reaction follows an SN2 pathway where the nucleophilic acetylide ion attacks the electrophilic carbon of the primary alkyl halide from the backside.
<img alt="Figure4" src="/files/ftp_upload/11834/11834_PT_Figure_4.svg" style="text-align: center; height: 250px;" />
Since this is a concerted process, the nucleophilic attack and the departure of the leaving group takes place simultaneously to form the product with an inverted stereochemistry at the reaction center.
The reaction works best with unhindered alkyl halides like methyl halide and other primary halides. With secondary and tertiary alkyl halides, acetylide ions act as strong bases, in which case E2 elimination is the preferred pathway.
<h4>Application in organic synthesis </h4>
Alkylation of simple terminal alkynes is a useful method to extend the length of the carbon chain. Acetylene, a terminal alkyne, can be converted to a higher internal alkyne by repeated alkylation as shown below:
<img alt="Figure5" src="/files/ftp_upload/11834/11834_PT_Figure_5.svg" style="text-align: center; height: 50px;" />

Preparación de alquinos: Reacción de alquilación

Introduction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for ...

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Alquinos

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Preparation of Alkynes: Dehydrohalogenation

<h4>Introduction</h4>
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
<img alt="Figure1" src="/files/ftp_upload/11835/11835_PT_Figure_1.svg" style="text-align: center; height: 200px;" />
<h4>Reaction Mechanism &#8211; E2 pathway</h4>
Vicinal dihalides
In the first elimination step, the strong base abstracts the proton from the dihalide that is oriented anti to the leaving group. Since E2 reactions follow a concerted pathway, the abstraction of a proton and departure of the halide leaving group occur simultaneously to form a haloalkene.
<img alt="Figure2" src="/files/ftp_upload/11835/11835_PT_Figure_2.svg" style="text-align: center; height: 90px;" />
In the second elimination reaction, another equivalent of the strong base reacts with the haloalkene in a similar fashion to give the desired alkyne.
<img alt="Figure3" src="/files/ftp_upload/11835/11835_PT_Figure_3.svg" style="text-align: center; height: 90px;" />
Geminal dihalides
Likewise, geminal dihalides, when treated with two equivalents of a sodium amide, undergo double dehydrohalogenation to give alkynes.
<img alt="Figure4" src="/files/ftp_upload/11835/11835_PT_Figure_4.svg" style="text-align: center; height: 90px;" />
<img alt="Figure5" src="/files/ftp_upload/11835/11835_PT_Figure_5.svg" style="text-align: center; height: 90px;" />
Terminal dihalides 
Dehydrohalogenation of terminal dihalides yields terminal alkynes as the final product. In the presence of a strong base like sodium amide, terminal alkynes get converted to acetylide ions. In such cases, a third equivalent of the base is required to complete the dehydrohalogenation of the remaining haloalkene.
<img alt="Figure6" src="/files/ftp_upload/11835/11835_PT_Figure_6.svg" style="text-align: center; height: 70px;" />
Protonation of the acetylide ions with water or an aqueous acid completes the reaction.
<img alt="Figure7" src="/files/ftp_upload/11835/11835_PT_Figure_7.svg" style="text-align: center; height: 50px;" />
<h4>Application in Organic Synthesis</h4>
Dehydrohalogenation of vicinal dihalides is a useful intermediate step in the conversion of alkenes to alkynes. For example, chlorination of 1-propene gives 1,2-dichloropropane &#8211; a vicinal dihalide, which upon double dehydrohalogenation yields 1-propyne.
<img alt="Figure8" src="/files/ftp_upload/11835/11835_PT_Figure_8.svg" style="text-align: center; height: 60px;" />
Similarly, alkynes can also be synthesized from ketones via dehydrohalogenation of geminal dihalides. For example, treatment of acetone with phosphorous pentachloride yields 2,2-dichloropropane &#8211; a geminal dihalide, which undergoes double dehydrohalogenation to give 1-propyne.
<img alt="Figure9" src="/files/ftp_upload/11835/11835_PT_Figure_9.svg" style="text-align: center; height: 80px;" />

Prepararación de alquinos: Deshidrohalogenación

Introduction
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ...