资助这项工程由美国化学学会石油研究基金（52488-DNI1）和北卡罗来纳大学格林斯伯勒分校深表感谢。我们还要感谢特里尼罗河博士（联合国宣传小组），以供外借我们适当的玻璃器皿这些实验。视频咨询和编辑由Aaron GLANCY也承认。

1。 HIAT苯的合成<ol><li>装备一个干燥的100毫升的圆底烧瓶中，用磁搅拌器搅拌，并有氩气气氛下的烧瓶中。钳瓶的立场，并将其放入乙腈和固体二氧化碳颗粒冷冻剂洗澡。注意:该制冷剂应为约-45℃。 </li><li>加入10毫升无水二氯甲烷中，冰冷烧瓶，并允许溶剂平衡到冷冻剂的温度。注意:在烧瓶中的过量的顶部空间是用于加入乙醚后，强制沉淀重要。 </li><li>权衡0.35克cyanophenyliodonium三氟甲磺酸酯（1当量），并迅速将其传送到冷烧瓶中。注意:将固体应该是相当不溶在此温度下。 </li><li>去皮的空注射器的质量，然后用它衡量0.37克phenylethynyltributyltin（1当量）。 </li><li>注入phenylethynyltributyltin在冷溶液。注:固体的溶解是一个迹象表明，该HIAT已经形成。大致时间为溶解30分钟。 </li><li>加入乙醚和己烷，迫使产品沉淀。注意:如果沉淀不形成，使溶剂蒸发，在减压下，加入乙醚和己烷，迫使HIAT的沉淀的混合物。 </li><li>装备保温瓶用布氏漏斗和解决方案倒到漏斗过滤。 </li><li>收集固体并存储在寒冷的不透明的容器。 </li></ol> 2。正戊基HIAT合成<ol><li>装备一个250毫升三颈圆底烧瓶中，用磁搅拌器搅拌，并有氩气气氛下的烧瓶中。钳瓶的立场，并将其放入乙腈和固体二氧化碳颗粒冷冻剂洗澡。注意:该制冷剂应为约-45℃。 </li><li>在烧瓶装配在Schlenk过滤装置，使得过滤，可以迅速地进行，并在一个冷统温度。油脂和该装置的每个关节夹紧在一起。注意:该过滤系统可通过几种方法来构造，但它是非常重要的，该系统具有推入惰性气体和拉带通过玻璃过滤器真空的能力。 </li><li>加入10毫升无水二氯甲烷中，冰冷烧瓶，并允许溶剂平衡到冷冻剂的温度。注意:在烧瓶中的过量的顶部空间是用于添加己烷后，强制沉淀重要。 </li><li>权衡0.35克cyanophenyliodonium三氟甲磺酸酯（1当量），并迅速将其传送到冷烧瓶中。注意:将固体应该是相当不溶在此温度下。 </li><li>去皮的空注射器的质量，然后用它衡量0.44克三丁基锡庚炔（1当量）。 </li><li>注入的三丁基庚炔进入冷溶液。注:固体的溶解是一个迹象表明，HIAT已经形成。大致时间为溶解30分钟。 </li><li>注入75毫升十六进制ANE到烧瓶中的额外顶部空间，以形成沉淀物。 </li><li>将收集烧瓶在真空下。 </li><li>从支架上松开的设备和精心倾斜，以解决倒到玻璃过滤器。打开收集瓶真空通过拉液体。注意:不要让真空拉空气进入血管。 </li><li>拆除设备刮固体过滤网一次过滤完成。一旦将固体从滤液中除去它是较少的空气和温度敏感的，并且可以被处理开放于空气中。 </li><li>收集固体并存储在寒冷的不透明的容器。 </li></ol> 3。俄亥俄州Cyanocarbenes制成苯基HIAT的插入<ol><li>装备一个干燥的50ml园底烧瓶用磁搅拌器搅拌，并有氩气气氛下的烧瓶中。夹紧烧瓶中搅拌板和注入20ml无水甲醇中，向烧瓶中。 </li><li>权衡先前甲醇合成为0.300克（1当量）。ZED苯基HIAT并迅速将其添加到烧瓶中。 </li><li>加0.047克的叠氮化钠（1当量）的烧瓶中。注:该解决方案将变暗随着时间的推移和氮​​气由cyanocarbene形成产生。 </li><li>让反应继续进行，只要形成气泡发生。大致完成时间为20分钟。 </li><li>暴露的溶液在空气中，用减压蒸发溶剂。 </li><li>加二氯甲烷的残留液体，并执行水萃取以除去钠三氟甲磺酸酯。收集二氯甲烷和干燥，用无水硫酸钠将有机相。 </li><li>滗出溶液，并用蒸发减压。 </li><li>进行柱层析净化cyanocarbene产品。 </li></ol> 4。使用苯基环丙烷HIAT反应Cyanocarbene <ol><li>称量四丁基铵叠氮化物在手套箱0.125克（1当量），并将其放置在干燥10毫升圆底烧瓶当量uipped用磁搅拌器搅拌。 </li><li>盖上含有叠氮化四丁基铵10毫升圆底烧瓶中，从手套箱中取出，并使用舒伦克线将其放置在搅拌下盘氩气。 </li><li>加入1.0 ml苯乙烯，向烧瓶中，并允许烧瓶搅拌。注:叠氮化物不需要溶解。 </li><li>快速添加0.200克苯基HIAT（1当量）到该浆料中，然后将隔膜背面上被连接到的Schlenk线烧瓶中。注:该解决方案应该立即变暗，由cyanocarbene形成产生氮气。 </li><li>使反应继续下去，只要形成气泡发生。大致完成时间为一分钟。 </li><li>之后，气泡停止后，露出溶液在空气中，进行柱色谱法提纯产物。 </li></ol>

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作者宣称，他们有没有竞争的财务权益。

高价碘炔基三氟甲磺酸酯，或HIATs，形成有可与叠氮化物源反应形成cyanocarbenes。这是非常重要的，所有必要的预防措施，因为许多在这个视频显示的试剂和中间体是可能发生爆炸和剧毒。虽然反应性的高的水平可能是危险的，如果准备不足，它表示在该播放该化合物的内在反应性可以通过捕获cyanocarbenes在各种反应如OH插入和环丙烷被利用。 其他HIATs的合成一直试图用不同的成...

有机化学的持续发展取决于新反应的设计和开发。尤其是，新的反应，使以前无法想象的合成路线的发现熊终极意义。为此目的，我们组随意转换炔的两个碳原子和一个叠氮化物的氮成cyanocarbene。1此以前未知的变换将允许在分子复杂显著增加，因为反应性cyanocarbene会迅速进一步反应。最初的努力是使用亲核炔和叠氮化物亲电的，但三唑被有效地形成在该情况下，而不是cyanocarbenes。2使用umpolung方法中，第二种方法是使用亲电炔和亲核叠氮化物和从cyanocarbene反应得到的产物是幸运的形成在该情况下，3有亲核叠氮化物的许多来源，然而，电炔烃是不太常见。本组克劳斯Banert先前报道证明了概念该反应使用炔基-氯，4但本集团与Banert组独立以及同时确定高价碘炔基三氟甲磺酸酯（HIATs）是原因好得多亲电稳定性和反应性。3,6我们这里所描述的合成，分离，和这些HIATs与叠氮化物的形成，并在原位作为cyanocarbenes反应反应。 几个安全预防措施，应继续进行这些实验之前予以考虑。一些高价碘炔基三氟甲磺酸酯是不稳定的，会发生分解，剧烈的某个时候，当暴露在空气和光线。7为了形成cyanocarbene中间，该过程需要使用叠氮化物的来源。叠氮化物是爆炸物和剧毒。8适当的个人防护装备应处理这些材料，特别是有机锡的时候可以穿，和所有操纵试剂应在适当通风罩。该cyanocarbene是一个强大的和不稳定的活性中间体。小心在小范围内开始进行实验，使氮气进化是可控的，从来没有在封闭系统中进行这些反应。如果规模化反应的需要，我们强烈建议使用安全防护罩。 先前已经发表了许多HIATs的合成被包括使用Zefirov的试剂9,10，和Koser试剂，9,11然而，这部影片将使用cyanophenyliodonium三氟甲磺酸酯试剂9,12（ 图1）。合成Cyanophenyliodonium三氟甲磺酸酯基上显示与先前报导的文献制备。与三烷基锡改性炔14 13的试剂反应，形成所需产物。后HIAT合成和分离它可以与叠氮化物反应，形成反应cyanocarbene中间（ 图2）。还有许多其他的方法可以用于合成碘炔烃，如使用炔基硅烷15和炔基硼酸酯16，但在视频的方法的原因是，在我们的经验，它有更好的效率和产率。 我们提出的机制3,5（ 图3），用于本反应包括加入叠氮化物源，以炔的β-碳，由此形成碘鎓盐的分解而碘苯和亚乙烯基碳烯。然后偏卡宾可以通过任一R-基团或酰基叠氮化物，得到炔基-叠氮化物的迁移发生的1,2 -重排。的炔基叠氮化物，然后挤出二氮以形成cyanocarbene可与衬底发生反应。应当指出，有可能是形成高价碘鎓三氟甲磺酸酯的链烯基物质的，这取决于条件。的副产品是利于在质子溶剂如碘鎓盐的质子化比重排的炔酰基叠氮化物更快更低的温度。在OH插入反应发生的另一种可能的产品是其中的偏卡宾的重排的炔基叠氮发生之前被困乙烯基醚。形成这种乙烯基醚的倾向是由R组决定。 之一的，该反应的主要优点是，卡宾反应后，将得到的腈基是一个方便的把手，进一步官能化。许多合成子可以设想用这种方法和不同的产品可以用相同的基板来形成。控制该产物混合物与温度，浓度，和R基团的炔是必要的。3含于cyanocarbenes如何表现适当的洞察，所述方法示出了一种可行的方法以快速增加化学的复杂性，以形成目标分子。如何cyanocarben的例子ë起反应包括OH插入其中的醇的亲核氧原子攻击卡宾，然后质子转移发生，二甲亚砜络合物，其中所述卡宾结合的硫原子，和环丙烷，其中卡宾反应与烯烃。

<table><tbody><tr><td colspan="4">&lt;strong&gt;Reagent&lt;/strong&gt;</td></tr><tr><td>Phenyl acetylene</td><td>Acros</td><td>AC152461000</td><td></td></tr><tr><td>Tri-n-butyltin chloride</td><td>Acros</td><td>139351000</td><td></td></tr><tr><td>Lithium bis(trimethysilyl)amide</td><td>Acros</td><td>347701000</td><td></td></tr><tr><td>Iodobenzene diacetate</td><td>Acros</td><td>176560250</td><td></td></tr><tr><td>Trimethylsilyl cyanide</td><td>Aldrich</td><td>212849</td><td>Extremely toxic. Handle this chemical only in an adequately ventilated hood with extreme caution.</td></tr><tr><td>Trimethylsilyl triflate</td><td>Alfa Aesar</td><td>A12535</td><td></td></tr><tr><td>Sodium Azide</td><td>Sigma-Aldrich</td><td>S8032</td><td>Shock sensitive.</td></tr><tr><td>Tetrabutylammonium azide</td><td>Aldrich</td><td>651664</td><td>If possible, store and handle in a glovebox due to this compound&amp;rsquo;s hygroscopic nature.</td></tr><tr><td>1-Heptyne</td><td>Acros</td><td>223460250</td><td></td></tr><tr><td>Styrene</td><td>Aldrich</td><td>240869</td><td></td></tr><tr><td colspan="4">[header]</td></tr><tr><td colspan="4">&lt;strong&gt;Material&lt;/strong&gt;</td></tr><tr><td>Rotary Evaporator (Hei-VAP)</td><td>Heidolph</td><td>517-61000-01-0</td><td></td></tr><tr><td>Glovebox</td><td>MBRAUN</td><td>UL-018</td><td></td></tr></tbody></table>

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

在这篇文章中所描述的程序涉及的高价碘炔基三氟甲磺酸酯（HIATs）及其与叠氮化物的后续反应的合成和隔离，形成cyanocarbene中间体。的高价碘炔基三氟甲磺酸酯的合成可以是浅显的，但问题是由于隔离和反应性干。特别是，惰性气氛下使用的过滤在-45℃下一些HIATs的必要性，需要特别照顾和设备。一旦分离，所述化合物可被存储和在反应中使用的叠氮化物用于形成cyanocarbene中间体。 的证据cyanocarbene代所表现出的双氮可见挤出以及从俄亥俄州插入，亚砜络合，环丙烷化中发生的产品的特性。该cyanocarbene形成的副反应是偏二卡宾的生成，并控制该过程的条件进行了讨论。有也可能形成一个高价碘鎓三氟甲磺酸烯并进行隔离，其发电的控制手段提供。的OH插入反应包括使用HIAT，叠氮化钠或四丁基铵叠氮化物，和以甲醇为溶剂/基质。亚砜配位反应使用HIAT，叠氮化钠或四丁基铵叠氮化物，和二甲亚砜作为溶剂。该cyclopropanations可以使用或不使用溶剂来进行。叠氮化物源必须是四丁基铵叠氮化物和所示的基板是苯乙烯。

图1示出HIAT的合成通过使用cyanophenyliodonium炔基三氟甲磺酸酯。该HIAT然后可以用来产生cyanocarbenes将经环丙烷的OH插入。与苯基HIAT的OH插入反应产生2 - 甲氧基-2 - 苯基乙腈在高达75％的产率。与苯基HIAT环丙烷反应生成1,2 - diphenylcyclopropanecarbonitrile在多达61％的产量。尽管在视频没有证明，二甲亚砜络合物可以与二甲亚砜进行反应，以产生DMSO-加合物在27％的产率，当与cyanocarbene中间发生...

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

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

本文中所描述的合成，分离，和超价碘炔基三氟甲磺酸酯（HIATs）反应，用叠氮化物，以产生cyanocarbenes。该程序将涉及空气敏感和制冷剂的技术，包括在惰性气氛下冷过滤。处理的合成的化合物及安全性也将被讨论。

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 ...

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

Research

JoVE Journal

Chemistry

10.8K 次观看.  University of North Carolina at Greensboro. 本文中所描述的合成，分离，和超价碘炔基三氟甲磺酸酯（HIATs）反应，用叠氮化物，以产生cyanocarbenes。该程序将涉及空气敏感和制冷剂的技术，包括在惰性气氛下冷过滤。处理的合成的化合物及安全性也将被讨论。 

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

Synthesis and Purification of Iodoaziridines Involving Quantitative Selection of the Optimal Stationary Phase for Chromatography

The highly diastereoselective preparation of cis-N-Ts-iodoaziridines through reaction of diiodomethyllithium with N-Ts aldimines is described. Diiodomethyllithium is prepared by the deprotonation of diiodomethane with LiHMDS, in a THF/diethyl ether mixture, at -78 &#176;C in the dark. These conditions are essential for the stability of the LiCHI2 reagent generated. The subsequent dropwise addition of N-Ts aldimines to the preformed diiodomethyllithium solution affords an amino-diiodide intermediate, which is not isolated. Rapid warming of the reaction mixture to 0 &#176;C promotes cyclization to afford iodoaziridines with exclusive cis-diastereoselectivity. The addition and cyclization stages of the reaction are mediated in one reaction flask by careful temperature control.
Due to the sensitivity of the iodoaziridines to purification, assessment of suitable methods of purification is required. A protocol to assess the stability of sensitive compounds to stationary phases for column chromatography is described. This method is suitable to apply to new iodoaziridines, or other potentially sensitive novel compounds. Consequently this method may find application in range of synthetic projects. The procedure involves firstly the assessment of the reaction yield, prior to purification, by 1H NMR spectroscopy with comparison to an internal standard. Portions of impure product mixture are then exposed to slurries of various stationary phases appropriate for chromatography, in a solvent system suitable as the eluent in flash chromatography. After stirring for 30 min to mimic chromatography, followed by filtering, the samples are analyzed by 1H NMR spectroscopy. Calculated yields for each stationary phase are then compared to that initially obtained from the crude reaction mixture. The results obtained provide a quantitative assessment of the stability of the compound to the different stationary phases; hence the optimal can be selected. The choice of basic alumina, modified to activity IV, as a suitable stationary phase has allowed isolation of certain iodoaziridines in excellent yield and purity.

A protocol for the diastereoselective one-pot preparation of cis-N-Ts-iodoaziridines is described. The generation of diiodomethyllithium, addition to N-Ts aldimines and cyclization of the amino gem-diiodide intermediate to iodoaziridines is demonstrated. Also included is a protocol to rapidly and quantitatively assess the most appropriate stationary phase for purification by chromatography.

合成和Iodoaziridines纯化涉及定量选择最优固定相的色谱

The highly diastereoselective preparation of cis-N-Ts-iodoaziridines through reaction of diiodomethyllithium with N-Ts aldimines is described. ...

科研

化学

Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts

Ynones are a valuable functional group and building block in organic synthesis. Ynones serve as a precursor to many important organic functional groups and scaffolds. Traditional methods for the preparation of ynones are associated with drawbacks including harsh conditions, multiple purification steps, and the presence of unwanted byproducts. An alternative method for the straightforward preparation of ynones from acyl chlorides and potassium alkynyltrifluoroborate salts is described herein. The adoption of organotrifluoroborate salts as an alternative to organometallic reagents for the formation of new carbon-carbon bonds has a number of advantages. Potassium organotrifluoroborate salts are shelf stable, have good functional group tolerance, low toxicity, and a wide variety are straightforward to prepare. The title reaction proceeds rapidly at ambient temperature in the presence of a Lewis acid without the exclusion of air and moisture. Fair to excellent yields may be obtained via reaction of various aryl and alkyl acid chlorides with alkynyltrifluoroborate salts in the presence of boron trichloride.

The goal of this manuscript is to demonstrate a straightforward method for the preparation of ynones from acyl chloride and potassium alkynyltrifluoroborate salt starting materials. The one-pot reaction proceeds rapidly in the presence of boron trichloride without exclusion of air and moisture.

Ynones从酰氯和钾Alkynyltrifluoroborate盐无金属合成

Ynones are a valuable functional group and building block in organic synthesis. Ynones serve as a precursor to many important organic functional groups ...

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

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

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

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

协议的合成<em&gt;邻</em&gt; -trifluoromethoxylated苯胺类化合物

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

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides, which react under a variety of conditions to afford useful N- and O-containing compounds. Acid-catalyzed addition of alcohols or thiols to N-(2-alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and thioketals, respectively. Selective reduction of the vinyl group in N-(2-alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the corresponding phthalan in good yield, whereas reduction with sodium bis(2-methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue. Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically versatile, but often hydrolytically unstable, this protocol emphasizes key techniques in preparing, handling, and reacting these pivotal substrates in several useful transformations.

Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Representative experimental procedures for the synthesis of N-(2-alkoxyvinyl)sulfonamides and subsequent conversion to phthalan and phenethylamine derivatives are presented in detail.

准备n-(2-alkoxyvinyl) 磺胺从n-tosyl-1,2,3-triazoles 和随后转换为取代 Phthalans 和 Phenethylamines

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile ...

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 ...

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. Recently, we have developed a two-step strategy for ketone enolate umpolung that has enabled the development of methods for chlorination, azidation, and amination using azoles. In addition, we have developed C-C bond&#8211;forming arylation and allylation reactions. At the heart of these methods is the preparation of the intermediate and highly reactive enolonium species prior to addition of a reactive nucleophile. This strategy is thus reminiscent of the preparation and use of metal enolates in classical synthetic chemistry. This strategy allows the use of nucleophiles that would otherwise be incompatible with the strongly oxidizing hypervalent iodine reagents. In this paper we present a detailed protocol for chlorination, azidation, N-heteroarylation, arylation, and allylation. The products include motifs prevalent in medicinally active products. This article will greatly assist others in using these methods.

A two step one-pot protocol for the umpolung of ketone enolates to enolonium species and addition of a nucleophile to the &#945;-position is described. Nucleophiles include chloride, azide, azoles, allyl-silanes, and aromatic compounds.

Enolonium 种极性转换酮功能化的两步协议

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. ...

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 ...

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 ...

Aldehydes and Ketones with HCN: Cyanohydrin Formation Overview

Cyanohydrins are compounds that contain &ndash;CN and &ndash;OH groups on the same carbon atom. They are formed by the nucleophilic addition of the cyanide ions to the carbonyl group. Cyanide ions are highly basic and nucleophilic and can be generated from HCN under aqueous conditions. However, since HCN is a weak acid, the number of cyanide ions generated is very small. Hence, a small amount of base or KCN/NaCN is added to HCN to increase the concentration of the cyanide ions in the reaction mixture.
Cyanohydrin formation is favored in the case of aldehydes and simple ketones. However, when the bulky groups are present in ketones, the ketone gets sterically hindered, and the equilibrium generally shifts to the left, favoring the reactant.
Cyanohydrins are the key intermediates in the synthesis of various organic compounds. Under acidic hydrolysis conditions, cyanohydrins can be converted into &#945;-hydroxy acids or &#945;,&#946;-unsaturated acids. The conversion to &#945;-hydroxy acids constitutes a key step in the Kiliani&ndash;Fischer synthesis of sugars. On the other hand, the reduction of cyanohydrin in the presence of lithium aluminum hydride gives a &#946;-amino alcohol.
Cyanohydrin also occurs in nature in the form of mandelonitrile in millipedes. Millipedes use mandelonitrile as protection against predators and other organisms. Upon release, the mandelonitrile gets converted into benzaldehyde and HCN, preventing other animals from approaching the millipede.

醛和酮与 HCN:氰醇形成概述

Cyanohydrins are compounds that contain &ndash;CN and &ndash;OH groups on the same carbon atom. They are formed by the nucleophilic addition of the ...