Name: Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes (Vídeo) | JoVE Journal
Uploaded: 2018-09-12T14:45:00.000+00:00
Duration: 9 min 54 s
Description: Aprenda a preparação quimiosseletiva de 1-iodoalquinos, 1,2-diiodoalquenos e 1,1,2-triiodoalquenos por iodinação oxidativa de alquinos terminais usando reagentes de iodo hipervalente. Este método verde oferece excelente seletividade.

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This work was supported by the National Nature Science Foundation of China (21502023).

1. Synthesis of 1-(Iodoethynyl)-4-Methylbenzene (2, 1-Iodoalkynes)
<ol>
	<li>Add 133 mg (0.36 mmol) of TBAI and 3 mL of CH3CN to a reaction tube that contains a magnetic stirring bar, which is open to air. Then, add 38 &#956;L (0.3 mmol) of p-tolylethyne to the mixture using a microsyringe.</li>
	<li>Add 96.6 mg (0.3 mmol) of PIDA to the vigorously stirred reaction mixture in 10 portions over a period of 20 min using a spatula.</li>
	<li>Stir the reaction mixture at room temperature for 3 h.</li>
	<li>Pour the resulting mixture into a separatory funnel that contains 30 mL of water, and quench with aqueous Na2S2O3 (10%, 0.5 mL). Extract the aqueous layer three times with 10 mL of ethyl acetate.</li>
	<li>Wash the combined organic layers with 10 mL of saturated brine and dry over anhydrous sodium sulfate (0.5 g).</li>
	<li>Filter off the sodium sulfate using a Buchner funnel, and concentrate the filtrate under reduced pressure to obtain the crude product.</li>
	<li>Purify the crude product by column chromatography on silica gel using hexane as the eluent; the pure product, 1-(iodoethynyl)-4-methylbenzene, is obtained as a light yellow liquid (71.9 mg, 99% yield; Rf = 0.79).</li>
	<li>Analyze the product by 1H and 13C NMR spectroscopy, and high-performance liquid chromatography (HPLC).</li>
</ol>
2. Synthesis of (E)-1-(1,2-Diiodovinyl)-4-Methylbenzene (3, 1,2-Diiodoalkenes)
<ol>
	<li>Add 124.5 mg (0.75 mmol) of KI and 1 mL of CH3CN to a reaction tube that contains a magnetic stirring bar, which is open to air. Then, add 38 &#956;L (0.3 mmol) of p-tolylethyne and 3 mL of H2O to the mixture via a microsyringe.</li>
	<li>Add 96.6 mg (0.3 mmol) of PIDA to the vigorously stirred reaction mixture in 10 portions over a period of 20 min using a spatula.</li>
	<li>Stir the reaction mixture at room temperature for 24 h.</li>
	<li>Pour the resulting mixture into a separatory funnel that contains 30 mL of water, quench with aqueous Na2S2O3 (10%, 1 mL), and extract the aqueous layer three times with 10 mL of ethyl acetate.</li>
	<li>Wash the combined organic layers with 10 mL of brine and dry over anhydrous sodium sulfate (0.5 g).</li>
	<li>Filter off the sodium sulfate using a Buchner funnel, and concentrate the filtrate under reduced pressure to obtain the crude product.</li>
	<li>Purify the crude product by column chromatography on silica gel using hexane as the eluent. The pure product, (E)-1-(1,2-diiodovinyl)-4-methylbenzene, is obtained as a light yellow liquid (111.9 mg, 98% yield; Rf = 0.84).</li>
	<li>Analyze the product by 1H and 13C NMR spectroscopy as well as HPLC.</li>
</ol>
3. Synthesis of 1-Methyl-4-(1,2,2-Triiodovinyl)benzene (4, 1,1,2-Triiodoalkenes)
<ol>
	<li>Add 133 mg (0.36 mmol) of TBAI and 1 mL of CH3CN to a reaction tube that contains a stirring bar, which is open to air. Then, add 38 &#956;L (0.3 mmol) of p-tolylethyne using a microsyringe.</li>
	<li>Add 96.6 mg (0.3 mmol) of PIDA to the vigorously stirred reaction mixture in 10 portions over a period of 20 min using a spatula. Stir the reaction mixture for 3 h at room temperature.</li>
	<li>Add 124.5 mg (0.75 mmol) of KI in 3 mL of H2O to the reaction mixture.</li>
	<li>Add 193.2 mg (0.6 mmol) of PIDA to the reaction mixture in 10 portions over a period of 20 min using a spatula. Stir the reaction mixture for another 3 h at room temperature.</li>
	<li>Add another 124.5 mg (0.75 mmol) of KI in 3 mL of H2O and 1 mL of CH3CN to the reaction mixture.</li>
	<li>Add another 193.2 mg (0.6 mmol) of PIDA to the reaction mixture in 10 portions over a period of 20 min using a spatula. Stir the reaction mixture for another 12 h at room temperature.</li>
	<li>Pour the resulting mixture into a separatory funnel that contains 30 mL of water, quench with aqueous Na2S2O3 (10%, 2 mL), and extract the aqueous layer three times with 10 mL of ethyl acetate.</li>
	<li>Wash the combined organic layers with 10 mL of brine and dry over anhydrous sodium sulfate (0.5 g).</li>
	<li>Filter off the sodium sulfate using a Buchner funnel, and concentrate the filtrate under reduced pressure to obtain the crude product.</li>
	<li>Purify the crude product by column chromatography on silica gel using hexane to get the pure product, 1-methyl-4-(1, 2, 2-triiodovinyl)benzene, as a yellow liquid (138.4 mg, 93% yield; Rf = 0.79).</li>
	<li>Analyze the product by 1H and 13C NMR spectroscopy as well as HPLC.</li>
</ol>
4. Determination of the Selectivity for the Mono-, Di-, or Tri-iodination of Terminal Alkynes by HPLC
Note: The selectivity for the mono-, di-, tri-iodination of the alkynes was determined by HPLC. HPLC was performed on an instrument using a 5 &#956;m, 4.6 mm &#215; 150 mm column, CH3CN/H2O = 75/25 (v/v) as the solvent, a flow rate of 1.0 mL/min, and a detector wavelength of &#955; = 254 nm.
<ol>
	<li>Preparation of the external standard solution for HPLC
	<ol>
		<li>Precisely weigh out 2 (1-(iodoethynyl)-4-methylbenzene; 9.58 mg, 39.58&#215;10-3 mmol), 3 ((E)-1-(1,2-diiodovinyl)-4-methylbenzene; 19.29 mg, 52.14&#215;10-3 mmol), and 4 (1-methyl-4-(1,2,2-triiodovinyl)benzene; 11.10 mg, 22.38&#215;10-3 mmol).</li>
		<li>Mix and dissolve these three compounds in 1 mL of CH3CN and dilute the stock solution 100 times before performing the HPLC separation.</li>
		<li>Determine the peak area ratio (%) of each product on HPLC chromatogram.</li>
		<li>Calculate the ratio of the molar absorptivity of each compound according to the following formula: 
		&#949;2 : &#949;3 : &#949;4 = A2/n2 : A3/n3 : A4/n4 
		where &#949; is the molar absorptivity, A the peak area, and n the molar weight.</li>
	</ol>
	</li>
	<li>Calculate the chemoselectivity according to the following formula: 
	n2 : n3 : n4 = A2/&#949;2 : A3/&#949;3 : A4/&#949;4</li>
</ol>

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<li>Kohlhepp, S. V., Gulder, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Hypervalent+iodine%28III%29+fluorinations+of+alkenes+and+diazo+compounds%3A+new+opportunities+in+fluorination+chemistry%5BTitle%5D)+AND+%22Chemical+Society+Reviews%22%5BJournal%5D)">Hypervalent iodine(III) fluorinations of alkenes and diazo compounds: new opportunities in fluorination chemistry.</a> Chemical Society Reviews. 45 (22), 6270-6288 (2016).</li>
<li>Hein, J. E., Tripp, J. C., Krasnova, L. B., Sharpless, K. B., Fokin, V. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Copper%28I%29-Catalyzed+Cycloaddition+of+Organic+Azides+and+1-Iodoalkynes%5BTitle%5D)+AND+%22Angewandte+Chemie+International+Edition%22%5BJournal%5D)">Copper(I)-Catalyzed Cycloaddition of Organic Azides and 1-Iodoalkynes.</a> Angewandte Chemie International Edition. 48 (43), 8018-8021 (2009).</li>
</ol>

The authors have nothing extraordinary to disclose.

1-Iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes can be chemoselectively synthesized using hypervalent-iodine reagents as efficient mediators for oxidative iodination(s). The most critical factors of these chemoselective iodination protocols are the nature and loading of the iodine source, as well as the solvent. For example, 1-iodoalkyne 2 was obtained as the major product (52% yield) when TBAI (2.5 equiv loading) was selected as the iodine source in combination with MeOH as the solvent (<stro...

Iodoalkynes and iodoalkenes are widely used important precursors and building blocks in organic synthesis1,2,3,4, biologically active substances, and useful in the synthesis of materials and complex molecules given the ease of converting the C-I bond5,6,7,8. In recent years, the oxidative iodination of terminal alkynes has attracted more attention to the synthesis of iodoalkyne and iodoalkene derivatives. So far, efficient methods that use metal catalysts9,10,11,12, hypervalent-iodonium catalysts13,14, an anodic oxidation system15, ionic liquid systems16, KI (or I2)-oxidant combinations17,18,19,20, ultrasound21, phase-transfer catalysts22, N-iodosuccinimide9,22,23,24,25, n-BuLi26,27,28,29,30,31, Grignard reagents32, and morpholine catalysts17,33,24,35&#160;have been developed for the iodination of alkynes. Recently, we have reported a practical and chemoselective protocol for the synthesis of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes36. The features of this method are green and practical: (1) the toxicity of hypervalent-iodine catalysts as oxidative functionalization reagents is low compared to other conventional heavy-metal-based oxidants37,38,39,40,41,42, and (2) TBAI and/or KI are used as iodine sources. In addition, our system affords excellent selectivity under mild conditions. The chemoselective synthesis of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes requires precise control over various factors, including the composition, the oxidant, the iodine source, and the solvent. Among these, the iodine source is the most important factor for the chemoselectivity of the reaction. After the screening of several types and loadings of the iodine source as well as the solvents, three methods were identified and established. Firstly, TBAI as an iodine source in combination with PIDA (TBAI-PIDA) is selective for the synthesis of 1-iodoalkynes. Alternatively, 1,2-diiodoalkenes are efficiently obtained using a KI-PIDA system. Both methods afford the corresponding products in high yield and high chemoselectivity. The corresponding tri-iodinationproducts, i.e., 1,1,2-triiodoalkenes, were obtained in good yield from the one-pot synthesis that combine the TBAI-PIDA and KI-PIDA systems36.
Here, we will demonstrate how the chemoselectivity for the iodination of terminal alkynes can be steered from 1-iodoalkynes to 1,2-diiodoalkenes and to 1,1,2-triiodoalkenes under similar reaction conditions, highlighting the precise control that can be exerted by judiciously choosing oxidant, iodine source, and solvent. For the development of this new synthetic technique, p-tolylethyne was used as a model substrate. Although the following protocols focus on the synthesis of 1-(iodoethynyl)-4-methylbenzene, (E)-1-(1,2-diiodovinyl)-4-methylbenzene, and 1-methyl-4-(1,2,2-triiodovinyl)benzene, these compounds are representative for 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes, respectively, i.e., the protocols are broad in scope, and the same techniques can be applied to the chemoselective iodination of aromatic and aliphatic terminal alkynes36.
Reagents employed in the chemoselective iodination of terminal alkynes and small deviations from the techniques described result in dramatic differences with respect to the target products. For instance, changing of iodine source from TBAI to KI and changing of solvent from CH3CN to a CH3CN-H2O has a dramatic impact on the chemoselectivity of the iodination. The detailed protocol aims at helping new practitioners in the field with the chemoselective iodination of terminal alkynes to avoid many common pitfalls during the synthesis of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes.

<table><tbody><tr><td>4-etiniltolueno, 98%</td> <td>D080006</td><td></td> <td>químico de energia</td></tr><tr><td>fenilacetileno, 98%</td> <td>W330041</td><td></td> <td>químico de energia</td></tr><tr><td>1-etinil-4-metoxibenzeno, 98%</td> <td>D080007</td><td></td> <td>química de energia</td></tr><tr><td>1-etinil-4-fluorobenzeno, 98%</td> <td>D080005</td><td></td> <td>química de energia</td></tr><tr><td>4- (trifluorometil) fenilacetileno, 98%</td> <td>química de energia</td><td></td><td></td>W320273</tr><tr><td>éster metílico do ácido 4-etinilbenzóico, 97%</td> <td>A020720</td><td></td> <td>químico de energia</td></tr><tr><td>3-aminofenilacetileno, 97%</td> <td>D080001</td><td></td> <td>químico de energia</td></tr><tr><td>3-butin-1-ol, 98%</td> <td>A040031</td><td></td> <td>químico de energia</td></tr><tr><td>Propargylacetate, 98%</td> <td>Químico de energia</td><td>L10031</td><td></td></tr><tr><td>iodeto de tetrabutilamônio, 98%</td> <td>de energia química</td><td></td><td></td>E010070</tr><tr><td>Iodeto de potássio, 98%</td> <td>de energia química</td><td>E010364</td><td></td></tr> <tr><td>(diacetoxiiodo) benzeno, 99%</td> <td>de energia química</td><td>A020180</td><td></td></tr><tr><td>acetonitrila, agitador magnético de grau HPLC</td><td>fischer</td><td>A998-4</td><td></td></tr><tr><td></td><td>Evaporador rotativo IKA</td><td></td><td></td></tr><tr><td></td><td>Buchi</td><td></td><td></td></tr><tr><td>Bruker AVANCE III 400 MHz Supercondutor Fourier</td><td>Bruker</td><td></td><td></td></tr><tr><td>Cromatografia líquida de alta eficiência</td><td>Shimadzu</td><td></td><td></td></tr></tbody></table>

chemoselective preparation of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes based on the oxidative iodination of terminal alkynes

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.

A síntese quimiosseletiva de 1-iodoalquinos, 1,2-diiodoalcenos e 1,1,2-triiodoalcenos baseada na iodinação oxidativa de p-toliletino é resumida na Figura 1. Todas as reações foram expostas ao ar. Todos os compostos neste estudo foram caracterizados por espectroscopia de RMN de 1H e 13C, espectrometria de massas e CLAE para determinar a estrutura do produto e a seletividade da reação, bem como para avaliar a pureza. Os produtos obtidos são es...

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.

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

Este método pode ajudar a responder a questões-chave na síntese orgânica sobre iodação quimiosseletiva de alcinos terminais para a síntese de um-iodoalcinos, um, dois-diiodoalcenos e um, um, dois-triiodoalcenos. Esta técnica é verde, prática e oferece excelente seletividade em condições amenas. Os catalisadores de iodo hipervalente são muito menos tóxicos do que os oxidantes à base de metais pesados, e TBAI e KI são fontes de iodo amplamente disponíveis e fáceis de usar.Embora esse método possa fornecer informações sobre a síntese quimiosseletiva de derivados iodoalcinos, ele também pode ser aplicado a outras reações, como síntese de materiais, intermediários e compostos biologicamente ativos. Para começar, coloque 133 miligramas de iodeto de tetrabutilamônio em um tubo de reação aberto equipado com uma barra de agitação magnética. Adicione três mililitros de acetonitrila de grau HPLC ao tubo.Em seguida, coloque 38 microlitros de p-toliletina em uma microsseringa, adicione-a ao tubo e comece a mexer vigorosamente a mistura a cerca de 1.000 rpm. Ao longo de 20 minutos, adicione 96,6 miligramas de diacetoxi iodobenzeno, ou PIDA, em 10 porções aproximadamente iguais em intervalos de d

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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

Um protocolo para o diastereosseletivo preparação de um pote de cis - N-Ts-iodoaziridines é descrito. A geração de diiodomethyllithium, além de N-Ts aldiminas e ciclização do amino-gem-di-iodeto intermediário para iodoaziridines é demonstrada. Também está incluído um protocolo para avaliar rapidamente e quantitativamente a fase estacionária mais adequada para a purificação por cromatografia.

Síntese e Purificação de Iodoaziridines Envolvendo Quantitative Seleção do Optimal fase estacionária para cromatografia

O objetivo deste manuscrito é demonstrar um método direto para a preparação de inonas a partir de materiais de partida de cloreto de acila e sal de alquiniltrifluoroborato de potássio. A reação de um pote ocorre rapidamente na presença de tricloreto de boro sem exclusão de ar e umidade.

Síntese livre de metais de Ynones da Acil cloretos de potássio e sais Alkynyltrifluoroborate

Líquidos iônicos (ILs) medeiam o acesso rápido, simples e barato a 1,6-cetoésteres em altas diastereosseletividades e bons rendimentos. O protocolo de reação é robusto e os 1,6-cetoésteres podem ser obtidos em escala de gramas após um protocolo de filtração simples. Além disso, os 1,6-cetoésteres são gelificadores potentes em solventes de hidrocarbonetos.

Síntese altamente Stereoselective de 1,6-cetoésteres Mediada por líquidos iônicos: A reacção de três componente permitindo o rápido acesso a uma nova classe de baixo peso molecular Gelators Peso

Um protocolo simples e prático para a adição eficiente do conjugado de brometos funcionalizados de monoorganozinc aos carbonilas α, β-insaturados cíclicos para fornecer centros quaternário do todo-carbono foi desenvolvido.

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

3-Aroyl-N-hidroxi-5-nitroindoles foram sintetizados por cicloadição de 4 nitronitrosobenzeno com uma alquino terminal conjugada em um procedimento térmico de um passo. A preparação do nitrosoarenno e das alquinonas foi adequadamente relatada e, respectivamente, por meio de procedimentos de oxidação na anilina correspondente e no alquinol.

Uma síntese direta, regioseletiva e atom-econômica de 3-Aroyl-N-hidroxi-5-nitroindoles por Cycloaddition de 4-Nitronitrosobenze com Alkynones

Dois métodos para atribuir os sinais de ressonância magnética nuclear de α e ε-dimetilamina de uma lisina N-terminal 13C-metilada redutora são descritos. Um método utiliza a seletividade induzida pelo pH da reação de metilação redutiva e o outro usa aminopeptidase para remover seletivamente a lisina N-terminal.

Métodos para identificar as ressonâncias de RMN da amina N-terminal 13C-dimetil em proteínas metiladas redutivamente

Proteínas anticongelantes (AFPs) se ligam a planos específicos de gelo para prevenir ou retardar o crescimento do gelo. A análise de afinidade de aviões de gelo baseada em fluorescência (FIPA) é uma modificação do método original de gravação de gelo para determinação de aviões de gelo ligados à AFP. Os AFPs são rotulados fluorescentemente, incorporados em cristais de gelo simples macroscópicos, e visualizados sob luz UV.

Determinando os planos de ligação de gelo de proteínas anticongelantes pela afinidade do plano de gelo baseado em fluorescência

Aqui, apresentamos um protocolo para a síntese de dois carbenos decorados com carbonila. O protocolo torna esses compostos interessantes prontamente disponíveis para químicos de todos os níveis de habilidade. Além da síntese desses dois carbenos, também é descrito seu uso na ativação do fósforo branco.

Preparação e Utilização de carbenos Carbonyl decorados na ativação de fósforo branco

Um procedimento para a preparação de meios de separação híbridos porosos compostos por um monólito de polímero macroporoso revestido internamente por um polímero de coordenação microporosa de alta área superficial é apresentado.

Preparação de altamente poroso Coordenação Polymer Revestimentos em macroporosas Polymer Monólitos para o enriquecimento avançado de Fosfopeptídeos

Aprenda a preparação quimiosseletiva de 1-iodoalquinos, 1,2-diiodoalquenos e 1,1,2-triiodoalquenos por iodinação oxidativa de alquinos terminais usando reagentes de iodo hipervalente. Este método verde oferece excelente seletividade.

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes (Vídeo) | JoVE Journal

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

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