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.功能化 2,15-Dimethylhexahelicene <ol><li> 2,15-dimethylhexahelicene的Dibromination <ol><li>称量的过氧化苯甲酰（BPO）（70％的0.356克（1.0毫摩尔）2,15-dimethylhexahelicene的，0.374克（2.1毫摩尔）新鲜重结晶ñ溴代琥珀酰亚胺的（NBS）和24毫克（0.07毫摩尔）（重量）与30％的水作为稳定剂）。将所有的固体在100毫升的Schlenk烧瓶中的磁搅拌棒。由气体抽空的三个周期之后在舒伦克线用惰性气体再填充氮气气氛下放置。 </li><li>添加21毫升四氯化碳（CCL 4）。脱气用相同的疏散/剧烈搅拌下，小心，以防止溶剂大量流失的溶液再填充处理（步骤1.1.1）。 </li><li>热回流（77℃）的油浴混合物4小时。检查通过1 H核磁共振（NMR）的反应。 3.7 PPM和4.0 ppm的笑之间双峰ULD出现。它们表明非对映-CH 2的存在-组（ 图1）。 </li><li>一旦完成，将混合物冷却至室温，并在真空下除去溶剂。建立充满液氮，以避免泵污染陷阱。 </li><li>再溶解在30ml二氯甲烷（DCM）中的粗，转移至圆底烧瓶中并用4克硅胶混合（典型地添加粗制重量5倍）。集中在旋转蒸发该混合物。 </li><li>在此期间，填充的 SiO 2层析，用己烷/乙酸乙酯（95:5）预先混合的柱（长度约20厘米，厚度为4.5厘米）作为流动相。该混合物添加到该塔的顶部，然后添加的砂（2厘米）的层。 </li><li>小心地倒在新的流动相，并在试管收集分数（通常每管20 ml和4毫升接近预期的产物洗脱）进行色谱法。检查用薄层色谱级分（TLC）具有相同的流动相（己烷/乙酸乙酯95:5）在UV光下和图像。预期的产物（4b）中应结合所有想要的级分并除去掉溶剂在旋转蒸发器后的0.35的保留因子（RF）洗脱，为黄色油状物。 334毫克应获得（产率65％）。 注:所有Schlenk技术，采用油浴将被广泛应用在大多数的协议加热和柱层析设置的，所以从现在开始，他们将不会被详细列出，只有少数的意见，必要的时候会被给予。 </li></ol></li></ol><img alt="图1" src="/files/ftp_upload/53954/53954fig1.jpg" /> 的 2,15 图 1 H-NMR谱（500 兆赫，CDCL 3）。 -dimethylhelicene（顶部）和后2 小时取等分新的信号，对应-CH 2 - 。在一个红色圆圈（底部）被描述<a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/53954/53954fig1large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <ol start="2"><li> 的2,15双（叠氮甲基）hexahelicene <ol><li>权衡的2,15二（溴甲基）hexahelicene和叠氮化钠0.390克（6毫摩尔）0.103克（0.2毫摩尔）。放置两个固体在装有磁力棒和氮气氛下，把50毫升的Schlenk烧瓶中。 </li><li>用5.2毫升水（H 2 O）混合8.6四氢呋喃（THF）中的溶液和溶剂的混合物倒入Schlenk烧瓶。脱气溶液。 </li><li>热回流（65℃）3小时。检查通过1 H-NMR进行反应。 -CH 2 -信号应转移到3.75分钟（ 图2）。 </li><li>随后，COOl倒混合物至室温，并在真空下除去THF。用50ml H 2 O稀释</li><li>将混合物转移到分液漏斗中并用40ml的DCM萃取三次。合并所有的有机相并用纯的 H 2 O（50ml）中洗涤。 </li><li>纯化，用己烷/乙酸乙酯（85:15）作为流动相经硅胶柱色谱法将粗在Rf = 0.38，得到对应于2,15二（偶氮甲基）hexahelicene黄色油状物（ 图5b）。 70毫克应获得（产率80％）。 </li></ol></li></ol><img alt="图2" src="/files/ftp_upload/53954/53954fig2.jpg" /> 图 2:1 H-NMR谱（500 兆赫，CDCL 3）4 B（上）和一等分 的 3小时 后取（底部）。注意脂肪族地区的变化。 <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/53954/53954fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 2.碗烯的功能化<ol><li> 碗烯的单溴化 <ol><li>权衡碗烯0.125克（0.5毫摩尔），新鲜重结晶的NBS 89毫克（0.5毫摩尔）和17毫克的金（III），氯化水合物。 </li><li>将所有化合物到10ml小瓶特为装有磁条微波反应，然后放入氮气氛用2颈圆底烧瓶中的帮助。 </li><li>新增7毫升1,2-二氯乙烷（DCE）和脱气的溶液。 </li><li>超声处理混合物2分钟，以分散金盐颗粒。 </li><li>热，在100℃的微波反应器2小时内。 </li><li>完成后，将粗转移到一个圆底烧瓶中并通过ROTAR除去溶剂ÿ蒸发。 </li><li>纯化通过在使用己烷作为流动相的 SiO 2凝胶柱色谱将粗。 注:Bromocorannulene（ 图4a）是在射频得到黄色固体= 0.38。 99毫克应获得（产率60％）。未反应的碗烯（3a）的可被回收并储存用于进一步的用途。这似乎在Rf = 0.29。 </li></ol></li><li> Bomocorannulene和乙炔基的Sonogashira偶联 <ol><li>称重49毫克（0.15毫摩尔）bromocorannulene的，[的PdCl 2（DPPF）49,50（DPPF是1,1-&#39;bis（diphenylphsphino）二茂铁，的CuI 3毫克（0.015毫摩尔）的11毫克（0.015毫摩尔）。 51 </li><li>将所有的固体在用磁棒沿的50ml Schlenk烧瓶中，并在氮气氛下放置。 </li><li>加入5.0毫升三乙胺（网3）和脱气混合物。 </li><li>最后，添加104微升（0.75毫摩尔）乙炔基的。 </li><li>超声处理混合物2分钟，以分散金属盐颗粒。 </li><li>热在85℃具周期超声处理24小时，以防止金属盐沉积。 注:混合物颜色变成黑色不久，表明钯（0）的存在。 </li><li>冷却至室温，并在真空蒸发的NEt 3。 </li><li>再溶解在20ml的DCM中，并通过柱色谱法在硅胶上用己烷洗脱纯化，得到黄色固体在Rf = 0.28对应于图5a。 41毫克应获得（产率78％）。 注意:如果该粗品通过在DCM硅藻土垫过滤，可能会得到一个合理的纯的样品，然而膦衍生物并不完全除去。 </li></ol></li><li> Ethynylcorannulene由TMS准备去保护 <ol><li>权衡5a的35毫克（0.10毫摩尔）和无水氟化钾7.3毫克（0.125毫摩尔）。 </li><li>将所有的固体在配备有磁力棒的50毫升Schlenk烧瓶ð氮气氛下放置。 </li><li>混合物4毫升THF和4ml甲醇（MeOH），并将混合物倾入Schlenk烧瓶。德加彻底。 </li><li>允许在室温下进行反应，通过用不透明薄膜覆盖它从光保持烧瓶程。通过查看3.48 ppm的检查通过1 H-NMR进行反应。对应-CCH必须出现的信号（ 图3）。 注意:虽然该化合物带有一个末端炔即反应性和容易分解，我们发现下述工作起来时没有问题。它是在自然光下进行。 </li><li>一旦完成，除去THF在真空下，并用10毫升水稀释，转移一切至分液漏斗。 </li><li>用DCM（3×15毫升）提取，在室温下结合在一个圆底烧瓶中所有的有机相并浓缩在旋 ​​转蒸发器，最终得到一个黄色固体对应于图6a。 27毫克应得到（定量的收率）。 </li></ol></li></ol><img alt="图3" src="/files/ftp_upload/53954/53954fig3.jpg" /> 图 3:1 H-NMR谱（500 兆赫，CDCL 3）5（上）和 6（底部）-CCH单是在一个红色的圆圈描绘<a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/53954/53954fig3large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 3.总装通过点击化学<ol><li>权衡硫酸铜 15.3毫克（0.035毫摩尔）5b的，6a的20.0毫克（0.073毫摩尔），1.4毫克（0.007毫摩尔）抗坏血酸钠盐，1.7毫克（0.007毫摩尔）·5H 2 O. </li><li>将所有的固体在装有上午50毫升Schlenk烧瓶agnetic棒和氮气气氛下放置。 </li><li>混合物3毫升H 2 O和12毫升THF，将混合物倾入Schlenk烧瓶。彻底脱气的解决方案。 </li><li>热在65℃3天与连接到烧瓶顶部的冷凝器和定期检查反应来控制温度，搅拌和溶剂体积。检查通过1 H-NMR进行反应。在3.48 ppm的所述信号应该消失并转移到7.27 ppm的指示乙炔碗烯的消耗和三唑单元的存在（ 图4）。 </li><li>完成后，除去THF在真空下并用20毫升水稀释，将混合物转移至分液漏斗。 </li><li>用DCM（3×20毫升）提取，在一个圆底烧瓶中合并所有的有机相并在旋转蒸发器中浓缩。 </li><li>纯化通过柱色谱法将粗在SiO 2上纯化，用己烷/乙酸乙酯（1:1），得到浅黄色固体在Rf = 0.59对应于7。 27毫克应获得（产率75％）。 </li></ol><img alt="图4" src="/files/ftp_upload/53954/53954fig4.jpg" /> 图 4:1 H-NMR谱（500 兆赫，CDCL 3）5 B 的 （顶部），6（ 中）和后 2 天（底部） 所采取的等分试样注在粗-CCH信号的消失。 <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/53954/53954fig4large.jpg" target="_blank">请点击此处查看该图的放大版本。</a>

The authors have nothing to disclose.

最终化合物7已经经过从非平面多芳前体6的步骤3和3 b相在每个反应中度到非常良好的产率被制备。在这条线路中观察到的主要限制是两个非平面多芳化合物的溴化。然而，在化合物4 中的情况下，自由碗烯的重要量可以回收用于进一步的用途。 4 b的合成是因为我们发现polybromination如?...

由于其特殊的几何形状，碗烯和helicenes是可以采用远平面的结构并以有趣的性质产生1-15在过去的几年中的分子，搜索分子受体碳纳米管和富勒烯的是一个非常活跃的领域16-19因，主要是，以20-28其潜在的应用作为用于有机太阳能电池，晶体管，传感器和其他装置的材料。在碗烯和富勒烯之间的形状的优良的互补吸引若干研究人员的注意与设计的目标能够通过分散的力量建立的超分子协会的分子受体。29-39 上述非平面多芳化合物的化学是类似于对完全平面分子描述的，但它是有时很难找到合适的条件，以实现期望的选择性和产率。40 </sup&gt;在这项工作中，我们提出通过应用在每一个研究实验室发现很容易和典型的技术具有与良好收益几步3多环芳烃单元的分子（7）的合成。该分子是非常重要的，因为它可以采用一个钳状构象建立与在溶液C 60 37良好的相互作用;并且它可以打开一个研究线作为手性得益于螺烯接头，这是一种手性分子更高的富勒烯的电位受体由于立体异构轴的存在。41-45然而，只有外消旋螺烯将在这项工作中使用。 在这一点上，合成这些受体的唯一限制是helicenes和corannulenes的制备中，因为它们不是可商购的。但是，按照新的方法发表在别处46-48它们可以以合适的量在一段合理的短周期来获得。

<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.

碗烯（3）和2,15-dimethylhexahelicene（3 b）项可能如下目前的方法46-48以直接的方式具有非常良好的收益率（ 图5）做好准备。两个共享一个公共分子，2,7-二甲基萘，作为起始原料，从而产生发散到最终分子的汇集合成。 <img alt="图5" src="/files/ftp_upload/53954/53...

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

在这里，我们提出了一个协议，以合成由三个非平面多环芳烃单位复杂的有机化合物，具有合理的收益率容易组装。

一个碗烯官能Hexahelicene的铜（Ⅰ）制备催化的非平面多环芳烃单位炔叠氮化物环加成

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 ...

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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 次观看.  Universidad de Valladolid. 在这里，我们提出了一个协议，以合成由三个非平面多环芳烃单位复杂的有机化合物，具有合理的收益率容易组装。 

视频: 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.

高价碘鎓炔基三氟甲磺酸酯的生成Cyanocarbenes的合成应用

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

科研

化学

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.

访问有价值的配体为支持过渡金属:1,2,3,4,5-五甲基环戊二烯的一种改进，中级规模制备

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.

稳定笼 Aziridinium 离子的制备及其开环 Azaheterocycles 的合成

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.

基于末端碘氧化炔烃的 1-Iodoalkynes、12-Diiodoalkenes、11、2 Triiodoalkenes 的 Chemoselective 制备

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.

分离游离卡本内斯、其混合二聚体和有机自由基

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.

功能化单有机硼化合物共轭法高效合成全碳第四纪中心

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.

用于区域选择性开环反应的连续双氮丙啶的制备

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;

通过铃木交叉偶联和烯烃硼羧化反应合成硼化布洛芬衍生物

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;" />

炔烃的制备:烷基化反应

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 ...

教育

有机化学

炔烃

关键术语与概念

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;" />

炔烃的制备:脱卤化氢

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