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. A funcionalização de 2,15-Dimethylhexahelicene <ol><li> Dibromination de 2,15-dimethylhexahelicene <ol><li> Pesar 0,356 g (1,0 mmol) de 2,15-dimethylhexahelicene, 0,374 g (2,1 mmol) de bromo-succinimida recristalizado recém-N (NBS) e 24 mg (0,07 mmol) de peróxido de benzoilo (BPO) (70% em peso com 30% de água como estabilizador). Coloque todos os sólidos num balão de Schlenk de 100 mL com uma barra de agitação magnética. Coloque sob atmosfera de azoto por três ciclos de evacuação de gás seguido de preenchimento de gás inerte na linha de Schlenk. </li><li> Adicionar 21 ml de tetracloreto de carbono (CCI4). Desgaseificar a solução por o mesmo evacuação / reenchimento processo (passo 1.1.1) com agitação vigorosa e cuidadosamente a fim de evitar a perda de massa de solvente. </li><li> Aquece-se ao refluxo (77 ° C) a mistura com um banho de óleo durante 4 horas. Verifique a reacção por ressonância magnética nuclear de 1H (RMN). Doublets entre 3,7 ppm e 4,0 ppm shoaparecem uld. Eles indicam a presença de diastereotópico -CH 2 - grupos (Figura 1). </li><li> Uma vez terminado, a mistura arrefecer até à temperatura ambiente e remover o solvente sob vácuo. Criar uma armadilha preenchido com nitrogênio líquido para evitar a contaminação da bomba. </li><li> Redissolve-se o produto bruto em 30 ml de diclorometano (DCM), transferir para um balão de fundo redondo e misturar com 4 g de gel de sílica (tipicamente adicionar 5 vezes o peso bruto). Concentra-se a mistura num evaporador rotativo. </li><li> Neste meio tempo, encher uma coluna (comprimento cerca de 20 cm e uma espessura de 4,5 cm) com SiO2 gel misturado previamente com hexano / acetato de etilo (95: 5) como fase móvel. Adicionar a mistura ao topo da coluna e, em seguida, adicionar uma camada de areia (2 cm). </li><li> Com cuidado, despeje na nova fase móvel e realizar a cromatografia através da recolha de fracções em tubos de ensaio (normalmente 20 ml por tubo e 4 ml perto da eluição produto esperado). Verificar fracções por cromatografia em camada fina(TLC) com a mesma fase móvel (hexano / acetato de etilo 95: 5) e uma imagem com luz UV. O produto pretendido (4b) deve eluir com um factor de retenção (Rf) de 0,35, como um óleo amarelo após a combinação de todas as fracções e queria remover-se o solvente no evaporador rotativo. 334 mg devem ser obtidos (rendimento de 65%). NOTA: Todas as técnicas de Schlenk, o uso de um banho de óleo para as configurações de cromatografia de aquecimento e colunas serão amplamente utilizados na maioria dos protocolos, por isso a partir de agora, eles não serão cobertos em detalhes e apenas alguns comentários, quando necessário, seja dado. </li></ol></li></ol><img alt="figura 1" src="/files/ftp_upload/53954/53954fig1.jpg" /> . Figura 1 1 H-RMN Os espectros (500 MHz, CDCl 3) de 2,15 -dimethylhelicene (parte superior) e uma alíquota tomada após 2 horas Novos sinais, correspondente a -CH 2 -.., são retratados em um círculo vermelho (inferior) <a href="https://www.jove.com/files/ftp_upload/53954/53954fig1large.jpg" target="_blank">Por favor clique aqui para ver uma versão maior desta figura.</a> <ol start="2"><li> Síntese de 2,15-bis (azidometil) hexahelicene <ol><li> Pesar 0,103 g (0,2 mmol) de 2,15-bis (bromometil) hexahelicene e 0,390 g (6 mmol) de azida de sódio. Coloque ambos os sólidos em um frasco de 50 ml Schlenk equipado com barra magnética e colocado sob atmosfera de azoto. </li><li> Misturar 8,6 ml de tetra-hidrofurano (THF) com 5,2 ml de água (H2O) e verter a mistura de solventes para o balão de Schlenk. Desgaseificar a solução. </li><li> Aquece-se ao refluxo (65 ° C) durante 3 h. Verifique a reacção por 1H-RMN. -CH 2 - sinais deve mudar para 3,75 ppm (Figura 2). </li><li> Depois, cool para baixo a mistura até à temperatura ambiente e remover o THF sob vácuo. Dilui-se com 50 ml de H 2 O. </li><li> Transferir a mistura para uma ampola de decantação e extrai-se três vezes com 40 ml de DCM. Combinar todas as fases orgânicas e lava-se com puro H2O (50 ml). </li><li> Purifica-se o produto em bruto por cromatografia em coluna sobre gel de sílica usando hexano / acetato de etilo (85:15) como fase móvel para dar um óleo amarelo, a Rf = 0,38 correspondente a 2,15-bis (azomethyl) hexahelicene (5b). 70 mg deve ser obtidos (rendimento de 80%). </li></ol></li></ol><img alt="Figura 2" src="/files/ftp_upload/53954/53954fig2.jpg" /> Figura 2: 1 H-RMN Os espectros (500 MHz, CDCl3) de 4 b (em cima) e uma alíquota tomada depois de 3 h(parte inferior). Observe as mudanças na região alifático. <a href="https://www.jove.com/files/ftp_upload/53954/53954fig2large.jpg" target="_blank">Por favor clique aqui para ver uma versão maior desta figura.</a> 2. A funcionalização da Corannulene <ol><li> Monobromination de Corannulene <ol><li> Pesar 0,125 g (0,5 mmol) de corannulene, 89 mg (0,5 mmol) de NBS recentemente recristalizado e 17 mg de ouro (III) hidrato de cloreto. </li><li> Coloque todos os compostos em um frasco de 10 ml especialmente concebidos para reacções de microondas equipado com uma barra magnética e, em seguida, colocado em atmosfera de azoto, com a ajuda de um balão de fundo redondo com duas tubuladuras. </li><li> Adicionar 7 ml de 1,2-dicloroetano (DCE) e desgaseificar a solução. </li><li> Sonicar a mistura durante 2 minutos para dispersar as partículas de sal de ouro. </li><li> O calor no interior do reactor de micro-ondas a 100 ° C durante 2 h. </li><li> Quando terminou, transferir o produto em bruto para um balão de fundo redondo e remover o solvente por rotarY evaporação. </li><li> Purifica-se o produto em bruto por cromatografia em coluna sobre gel de SiO2, utilizando hexano como fase móvel. NOTA: Bromocorannulene (4a) é obtido na forma de um sólido de cor amarela, a Rf = 0,38. 99 mg deve ser obtidos (rendimento de 60%). Corannulene que não reagiu (3a) pode ser recuperado e armazenado para outras utilizações. Ele aparece a um Rf = 0,29. </li></ol></li><li> Acoplamento de Sonogashira de Bomocorannulene e etiniltrimetilsilano <ol><li> Pesar 49 mg (0,15 mmol) de bromocorannulene, 11 mg (0,015 mmol) de [PdCl2 (dppf)] 49,50 (dppf sendo 1,1-&#39;bis (diphenylphsphino) ferroceno, 3 mg (0,015 mmol) de Cul. 51 </li><li> Coloque todos os sólidos num num frasco Schlenk de 50 ml junto com uma barra magnética e colocar sob atmosfera de azoto. </li><li> Adicionar 5,0 ml de trietilamina (NEt3) e desgaseificar a mistura. </li><li> Finalmente, adicionar 104 ul (0,75 mmol) de etiniltrimetilsilano. </li><li> Sonicar a mistura durante 2 min adispersar partículas de sal de metal. </li><li> Aquece-se a 85 ° C durante 24 h com ultra-sons periódica para evitar a deposição de sais metálicos. NOTA: A mistura tornou-se de cor para preto em breve, indicando a presença de paládio (0). </li><li> Arrefecer até à temperatura ambiente e evapora-se NEt 3 em vácuo. </li><li> Redissolve-se em 20 ml de DCM e purifica-se por cromatografia em coluna sobre gel de sílica eluindo com hexano para dar um sólido de cor amarela, a Rf = 0,28 correspondente a 5a. 41 mg deve ser obtidos (rendimento de 78%). NOTA: Se o produto em bruto é filtrado através de uma almofada de Celite em DCM, pode ser obtida uma amostra pura razoável, contudo derivados de fosfina não são removidos totalmente. </li></ol></li><li> Preparação de Ethynylcorannulene por desprotecção TMS <ol><li> Pesar 35 mg (0,10 mmol) de 5-A e 7,3 mg (0,125 mmol) de fluoreto de potássio anidro. </li><li> Coloque todos os sólidos num balão de Schlenk de 50 ml equipado com uma barra magnética de umd colocado sob atmosfera de azoto. </li><li> Mistura-se 4 ml de THF e 4 ml de metanol (MeOH) e derramar a mistura para dentro do balão de Schlenk. Degas completamente. </li><li> Deixar reagir à temperatura ambiente, mantem o balão ao abrigo da luz, cobrindo-o com uma película opaca. Verifique a reacção por 1H-RMN, olhando para 3,48 ppm. Um sinal correspondente a -CCH deve surgir (Figura 3). NOTA: Embora este composto tem uma alcino terminal que é reativo e decompõe facilmente, não encontramos problemas durante o trabalho de descrito abaixo. Foi realizado sob luz natural. </li><li> Uma vez terminado, remover o THF sob vácuo e dilui-se com 10 ml de água, transferindo tudo para um funil de separação. </li><li> Extrai-se com DCM (3 x 15 mL), combinam todas as fases orgânicas, num balão de fundo redondo e concentra-se num evaporador rotativo à temperatura ambiente para finalmente obter um sólido amarelo correspondente a 6a. 27 mg deve ser obtidos (rendimento quantitativo). </li></ol></li></ol><img alt="Figura 3" src="/files/ftp_upload/53954/53954fig3.jpg" /> Figura 3:.. 1 H-NMR espectro (500 MHz, CDCl3) de 5-A (superior) e 6-A (baixo) singlet -CCH é retratado em um círculo vermelho <a href="https://www.jove.com/files/ftp_upload/53954/53954fig3large.jpg" target="_blank">Por favor clique aqui para ver uma versão maior desta figura.</a> 3. Montagem Final por Click Química <ol><li> Pesar 15,3 mg (0,035 mmol) de 5-B, 20,0 mg (0,073 mmol) de 6a, 1,4 mg (0,007 mmol) de sal de sódio de ácido ascórbico, 1,7 mg (0,007 mmol) de CuSO 4 5H 2 O. · </li><li> Coloque todos os sólidos num balão de Schlenk de 50 ml equipado com AMbar agnetic e colocado sob atmosfera de azoto. </li><li> Misturar 3 ml de H2O e 12 ml de THF e derramar a mistura para dentro do balão de Schlenk. Desgaseificar a solução completamente. </li><li> Aquece-se a 65 ° C durante 3 dias, com um condensador ligado ao topo do frasco e verificar periodicamente a reacção para controlar a temperatura, agitação e o volume de solvente. Verifique a reacção por 1H-RMN. O sinal a 3,48 ppm deve desaparecer e ser desviado para 7,27 ppm indicando o consumo de corannulene etinilo e a existência da unidade triazole (Figura 4). </li><li> Quando terminado, remover o THF sob vácuo e dilui-se com 20 ml de água, transferindo a mistura para um funil de separação. </li><li> Extrai-se com DCM (3 x 20 mL), combinam todas as fases orgânicas, num balão de fundo redondo e concentra-se num evaporador rotativo. </li><li> Purifica-se o produto em bruto por cromatografia em coluna sobre gel de SiO 2 eluindo-se com hexano / acetato de etilo (1: 1) para dar um sólido amarelo pálido, a Rf = 0,59correspondente a 7. 27 mg deve ser obtidos (rendimento de 75%). </li></ol><img alt="Figura 4" src="/files/ftp_upload/53954/53954fig4.jpg" /> Figura 4: 1 H-RMN Os espectros (500 MHz, CDCl3) de 5 b (parte superior), 6 um (meio) e uma alíquota tomada depois de 2 dias (inferior) Nota o desaparecimento do sinal a -CCH em bruto.. <a href="https://www.jove.com/files/ftp_upload/53954/53954fig4large.jpg" target="_blank">Por favor clique aqui para ver uma versão maior desta figura.</a>

The authors have nothing to disclose.

O composto final 7 foi preparado após 6 passos a partir de precursores poliaromáticos não planares e um 3 3 b com moderada a muito bons rendimentos de cada reacção. A principal limitação observada nesta via foi a bromação de ambos os compostos poliaromáticos não planas. No entanto, no caso de um composto 4, uma quantidade importante de corannulene livre pode ser recuperada para outras utiliza...

Devido à sua geometria especial, corannulene e helicenes são moléculas que podem adoptar uma estrutura longe de planaridade e dão origem a propriedades interessantes. 1-15 Nos últimos anos, a pesquisa de receptores moleculares de nanotubos de carbono e fulerenos é uma área muito activa 16-19, devido, principalmente, às suas potenciais aplicações como materiais para células solares orgânicas, transistores, sensores e outros dispositivos. 20-28 a excelente complementaridade em forma entre corannulene e um fulereno têm atraído a atenção de vários pesquisadores, com o objetivo de projetar receptores moleculares capazes de estabelecer associação supramolecular pelas forças de dispersão. 29-39 A química dos compostos poliaromáticos não planares acima mencionados é semelhante ao descrito para moléculas totalmente planas, mas às vezes é difícil encontrar condições adequadas para a realização selectividades e os rendimentos desejados. 40 </sup&gt; Neste trabalho apresentamos a síntese de uma molécula (7) que tem três unidades poliaromáticos em poucos passos com bons rendimentos através da aplicação de técnicas simples e típicos encontrados em cada laboratório de pesquisa. A molécula é de grande importância porque pode adotar uma conformação tipo tenaz para estabelecer boas interações com C 60 37 em solução; e que pode abrir uma linha de pesquisa como um receptor potencial para maiores fulerenos quirais graças ao ligante helicene, que é uma molécula quiral, devido à existência de um eixo estereogénico. 41-45 No entanto, apenas helicene racémica será usado neste trabalho. Neste ponto, a única limitação para sintetizar estes receptores é a preparação de helicenes corannulenes e, uma vez que não estão disponíveis comercialmente. Mas, de acordo com novos métodos publicados em outras posições 46-48 que pode ser obtido em quantidades adequadas num curto período de tempo razoável.

<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) e 2,15-dimethylhexahelicene (3 b) pode ser preparado seguindo os métodos actuais 46-48 de uma forma simples com muito bons rendimentos (Figura 5). Ambos compartilham uma molécula comum, 2,7-dimetilnaftaleno, como o material de partida, dando origem a um divergente de síntese convergente da molécula final. <...

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

Aqui, apresentamos um protocolo para sintetizar um composto orgânico complexo composto de três unidades poliaromáticos não planas, montadas facilmente com rendimentos razoáveis.

Preparação de um Hexahelicene Corannulene-funcionalizado por cobre (I) catalisada por cicloadição alcino azida de unidades não planar aromáticos policíclicos

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

Research

Education

JoVE Core

JoVE Journal

Organic Chemistry

Chemistry

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 visualizações.  Universidad de Valladolid.  Aqui, apresentamos um protocolo para sintetizar um composto orgânico complexo composto de três unidades poliaromáticos não planas, montadas facilmente com rendimentos razoáveis. 

Vídeo: 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.

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 ...

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.

Acesso a Suportes de Ligantes Valiosos para Metais de Transição: Preparação Modificada em Escala Intermediária de 1

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.

Preparação de Íons Aziridínio Bicíclicos Estáveis e sua Abertura de Anel para a Síntese de Azaheterociclos

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.

Preparação Quimiosseletiva de 1-iodoalquinos, 1,2-diiodoalqueenos e 1,1,2-triiodoalqueenos Baseada na Iodação Oxidativa de Alquinos Terminais

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.

Isolando carbenos livre, misto de dímeros e radicais orgânicos

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.

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 ...

Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions

The interest on nitrogen-containing heterocycles has expanded rapidly in the synthetic community since they are important motifs for new drugs. Traditionally, they were synthesized through thermal cycloaddition reactions, whereas today, photocatalysis is preferred due to the mild and efficient conditions. With this focus, a new photocatalytic method for the synthesis of nitrogen-containing heterocycles is highly desired. Here, we report a protocol for the biosynthesis of cercosporin, which could function as a metal-free photocatalyst. We then illustrate cercosporin-photocatalyzed protocols for the synthesis of nitrogen-containing heterocycles 1,2,3-thiadiazoles through annulation of azoalkenes with KSCN, and synthesis of 1,4,5,6-tetrahydropyridazines [4+2] through cyclodimerization of azoalkenes under mild conditions, respectively. As a result, there is a new bridge between the microbial fermentation method and organic synthesis in a mild, cost-effective, environmentally friendly and sustainable manner.

New routes for the synthesis of nitrogen-containing heterocycles utilizing cercosporin as a metal-free photocatalyst were developed.

Cercosporina-Fotocatalyzed [4+1]- e [4+2]-Anulações de Azoalkenes em Condições Leves

The interest on nitrogen-containing heterocycles has expanded rapidly in the synthetic community since they are important motifs for new drugs. ...

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.

Preparação de bisaziridinas contíguas para reações regiosseletivas de abertura de anéis

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;

Síntese de um Derivado Borilado de Ibuprofeno através de Reações de Acoplamento Cruzado Suzuki e Boracarboxilação de Alceno

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;" />

Preparação de Alquinos: Reação de Alquilação

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 ...