We gratefully acknowledge the Swedish Research Council Formas for generous financial support.

甲基-6-氧代-3,4,6- triphenylhexanoate 1.革兰氏规模合成<ol><li>干1-乙基-3-甲基咪唑鎓乙酸盐（EMIMAc）在10毫巴，40℃下1小时，在旋转蒸发器的圆底烧瓶中。 </li><li>添加2.1克干燥EMIMAc和1.0克1,3-二苯基-2-丙烯-1-酮向100毫升圆底烧瓶配备有磁力搅拌器。 </li><li>添加2.019毫升甲醇和2.3克肉桂烧瓶中。 </li><li>在室温（22℃）搅拌1分钟溶解在60毫升二氯甲烷的混合物中。 </li><li>接着添加0.37 ml的1.8二氮杂二环[5.4.0]十一-7-烯（DBU）到搅拌的混合物（步骤1.4）和帽的圆底烧瓶中。 </li><li>搅拌，在500rpm在室温（22℃）的速度一磁力搅拌棒。 </li><li>检查用 1 H-NMR。24查找在7.8 ppm的区域中的查耳酮的双键消失反应完成。 </li><li>当该反应达到<html>完成除去挥发旋转蒸发器上在10毫巴，20℃下进行15分钟。 </li><li>加入50毫升甲醇向残余物通过有磁性搅拌棒搅拌以溶解EMIMAc。 </li><li>通过用磁力搅拌棒搅拌下剧烈在750 rpm的速度为30分钟，除去从烧瓶壁上的固体。如果有必要，用刮刀从墙上去除剩余的固体。 </li><li>过滤器玻璃料（孔径3）的混合物。 </li><li>用另外20ml甲醇洗。如果回收EMIMAc的期望蒸发甲醇滤液。 （步骤2.1）。 </li><li>仍然在玻璃料上，轻轻地划分滤饼（从步骤1.11）成较小的块用刮勺和经由粉末漏斗转移到固体预称重的圆底烧瓶中，并在真空下干燥固体。 </li><li>称量烧瓶并计算产率。 </li><li>由1 H NMR（步骤1.7）分析产物。有报道光谱进行比较。24 </li></ol>EMIMAc的标题"&gt; 2。循环<ol><li>在10毫巴减压除去从甲醇混合物（来自步骤1.12）挥发物，在40℃下30分钟。 </li><li> 通过 1 H NMR和13 C-NMR分析所得的油，以检查EMIMAc存在。24 </li><li>使用回收EMIMAc从步骤1.2开始。 </li></ol> 3.凝胶<ol><li>储备溶液的制备<ol><li>加入200毫克甲基-6-氧代-3,4,6- triphenylhexanoate（从步骤1.15的产物）和磁搅拌棒至小瓶的。加入2.0毫升二氯甲烷中，以溶解酮酯。搅拌，直到一切都已经解散。 </li></ol></li><li>凝胶<ol><li>加入50毫升庚烷，以500毫升烧杯中。添加1.5 ml的储备溶液的庚烷。搅拌迅速，以确保充分混合，静置而不直至凝胶化发生在环境温度下搅拌。 </li></ol></li></ol>

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The authors have nothing to disclose.

基于由酮酯3的X射线分析和对所提出的Bode和同事30的机械调查确定反 -构型的下述反应路径建议（图5）。白细胞介素脱质子产生NHC种;所述NHC反应与不饱和醛形成布瑞斯罗夫中间体I中布瑞斯罗夫中间和在跨安息香反应的查耳酮反应形成二烯二。中级II经过转乘船过渡态（TS）的氧Cope重排，设置防取向的手性中心III。互变异构之后，酰基氮鎓IV与甲醇反应来交付产品和再生的催化剂。 <img alt="图5" src="/files/ftp_upload/53213/53213fig5.jpg" /> 图5:NHC催化加成查耳酮向肉桂醛催化周期（R =甲基等）。回覆-与许可参考24打印。 重要性的关键步骤是试剂的加入顺序。如果DBU不添加作为最后的试剂的反应产率往往会变得非常低。此外，还建议以蒸发EMIMAc使用前以来的挥发性物质存在于EMIMAc剩余量可能导致副产物。在洗涤步骤中的产物（1.12）的大块必须粉碎，以获得足够纯的材料。 故障排除凝胶状态是亚稳态和凝胶不可避免地成为颗粒感随着时间的推移。然而，如果凝胶是颗粒状直接形成后一个可能的原因是，该凝胶化在一个传导到高胶凝剂的浓度。 目前，反应需要用的EMIMAc，醛和甲醇过量，以实现高转化进行。从效率的角度来看这是任一试剂的不是最佳的，但较低的负载导致降低反应收率。 1,6-酮酯的合成是高度立体选择性，继续以优良的产量。此外，一个有效的洗涤协议呈现，而不需要溶剂苛刻色谱纯酮酯的最终产品。替代方法来选择性地访问高度官能1,6-酮酯是相当多的费力。 鉴于容易合成的1经由三组分反应，介绍的方法提供了快速的方式来产生分子多样性。结合1的效力作为有机凝胶剂，这种技术因此可以用于1,6-酮酯为一类新的LMWG的快速评估。该方法允许生产定制胶凝剂具有理想的性质，从而能够获得新的材料。

<img alt="TOC 1" src="/files/ftp_upload/53213/53213TOC.jpg" /> （以上）的1,6-酮酯三组分合成:一类新的低分子量胶凝剂。 离子液体（离子液体）具有高稳定性，低挥发性，不可燃性，并因此呈现关注，因为安全的反应介质和理想的溶剂进行回收。1-3二烷基咪唑鎓是一个特定类型的离子液体，在碱的存在下可以去质子化，以使一个N-杂环卡宾（NHC）。4在有机催化的领域中，的NHCs，根据不同的反应路径操作时，已经被广泛的使用在广泛的通用反应。5-11 尽管如此，ILS和CC键formin之间的连接摹NHC催化相对未开发的。尽管如此，从的NHCs离子液体衍生已经报道了催化CC键形成反应，如苯偶姻缩合和施德达反应。12-22。例如，Davis等人已经表明，从N-烷基thiazoliums衍生离子液体作为在预催化剂形成苯甲醛安息香12 最近，Chen和同事扩展使用基于IL咪唑这个概念，1-乙基-3-甲基咪唑鎓乙酸盐（EMIMAc），对5-羟甲基糠醛（HMF）执行安息香缩合以生成5,5&#39; -二（羟甲基）furoin（DHMF）。23由于离子液体可以买到，报价产生NHC的的一种廉价的方式，我们有兴趣在研究什么其他类型的反应，离子液体可以执行。为此，我们发现，二烷基咪唑鎓可有效用作在正规共轭additi预催化剂上的不饱和醛以查耳酮（图1），得到1,6-酮酯。最有效的IL，EMIMAc，促进肉桂醛和查尔之间的高立体选择性反应。发生反应以高偏爱反 -非对映和1,6-酮酯可以分离在产率高达92％。24,25,26 <img alt="图1" src="/files/ftp_upload/53213/53213fig1.jpg" /> 图1:IL-介导的三组分，立体选择性加成肉桂醛以查耳酮。

<table><tbody><tr><td>1-ethyl-3-methyl imidazolium acetate</td><td>Aldrich</td><td>51053-100G-F</td><td>Produced by BASF &amp;ge;90%, dried on a rotary evaporated before use (10 mBar, 40 &amp;deg;C, 1 hr)&lt;br/&gt; CAS NUMBER: 143314-17-4</td></tr><tr><td>1,3-diphenyl-2-propen-1-one</td><td>Aldrich</td><td>11970-100G</td><td>98.0%&lt;br/&gt; CAS NUMBER: 94-41-7</td></tr><tr><td>trans-cinnamaldehyde&amp;nbsp;</td><td>Aldrich</td><td>C80687-25G</td><td>99%, stored under nitrogen prior to use&lt;br/&gt; CAS NUMBER: 14371-10-9</td></tr><tr><td>1,8-Diazobicyclo[5.4.0]undec-7-ene</td><td>Aldrich</td><td>139009-25G</td><td>98%&lt;br/&gt; CAS NUMBER: 6674-22-2</td></tr><tr><td>Methanol</td><td>Sigma-Aldrich</td><td>32213N-2.5L</td><td>puriss. P.a., ACS reagent, reag. ISO, reag. Ph. Eur. &amp;ge;99.8% (GC)&lt;br/&gt; CAS NUMBER: 67-56-1</td></tr><tr><td>Dichloromethane</td><td>Fischer Chemical</td><td>D/1852/17X</td><td>Analytic reagent grade, stabilized with amylene&lt;br/&gt; CAS NUMBER: 9/2/1975</td></tr><tr><td>n-Heptane</td><td>Fischer Chemical</td><td>H/0160/17X</td><td>Analytic reagent grade&lt;br/&gt; CAS NUMBER: 142-82-5</td></tr></tbody></table>

highly stereoselective synthesis of 1,6-ketoesters mediated by ionic liquids: a three-component reaction enabling rapid access to a new class of low molecular weight gelators

In organic chemistry ionic liquids (ILs) have emerged as safe and recyclable reaction solvents. In the presence of a base ILs can be deprotonated to form catalytically active N-Heterocyclic Carbenes (NHCs). Here we have used ILs as precatalysts in the addition of &#945;,&#946;-unsaturated aldehydes to chalcones to form 1,6-ketoesters, incorporating an anti-diphenyl moiety in a highly stereoselective fashion. The reaction has a broad substrate scope and several functional groups and heteroaromatics can be integrated into the ketoester backbone in generally good yields with maintained stereoselectivity. The reaction protocol is robust and scalable. The starting materials are inexpensive and the products can be obtained after simple filtration, avoiding solvent-demanding chromatography. Furthermore, the IL can be recycled up to 5 times without any loss of reactivity. Moreover, the 1,6-ketoester end product is a potent gelator in several hydrocarbon based solvents. The method enables rapid access to and evaluation of a new class of low molecular weight gelators (LMWGs) from recyclable and inexpensive starting materials.

如上述例举EMIMAc充当在正规共轭加成α，β不饱和醛与查耳酮一个前段催化剂。其它市售咪唑鎓基的离子液体，例如1-乙基-3-甲基咪唑氯化物（EMIMCl）和1-丁基-3-甲基咪唑氯化物（BMIMCl）也进行了研究，然而，这些反应进行较低的产率，表明乙酸根阴离子可以是为反应性（ 表1，进入1-3）很重要。27,28 * *阴离子该反应中的作用是在目前还不清楚。关于阴离子的NHC催化的作用的研究看，引用图27和28。 <img alt="表格1" src="/files/ftp_upload/53213/53213table1highres.jpg" width="700" /> 表1:反应条件的1合成优化。 A和B是比EMIMAc效率较低，在33％和46％的收率，分别酮酯1，得到（表1，条目4和6）。此外，实现了高效的反应中使用的共溶剂是必要的，其中共溶剂提供由既溶解IL和最终产品均相反应。作为助溶剂，二氯甲烷提供关于反应收率最好的结果。努力找到一个更良性的溶剂制成;甲醇和乙腈也是可能的作为助溶剂，但在较低的产率（表1，条目7和8）为代价来使用。碱的选择也很重要，不加入碱没有反应可以观察到（表1，条目9）。 DBU被认为是最佳的底座（表1，第1项），但碳酸基地也是可行的充分转化在1.5小时，但具有较高程度的Ô˚F副产物形成（表1，条目11，72％产率）。温和碱如三乙胺只给了微量的产物（ 表1，条目10）的量。此外，该IL的单个组分介导的三组分反应可以变化以介绍几个官能团的酮酯主链。查耳酮轴承供电子基团和卤素取代基的耐受性良好，并继续在高DR和良好的产率（图2，条目2-10）。例如，酮酯6轴承在芳环上一个溴取代基，一个方便的支架用于交叉偶联化学，可以分离产率为75％。该α，β不饱和醛也可以改变，允许引进上的酮酯主链上的氯，甲基和甲氧基的基团，而不会影响选择性或收率（图2，条目11-13）。此外，不同的伯​​醇，如乙醇和苄醇可以一<html> LSO被引入（图2，条目14和15）。 <img alt="图2" src="/files/ftp_upload/53213/53213fig2.jpg" /> 图2:（2.5当量） 的正式共轭加成α，β不饱和醛到查耳酮的反应范围 （ 一 ）。反应在RT，二氯甲烷，加入DBU（0.5当量），白细胞介素进行，醛（3当量） ，查耳酮（1当量0.08 M），醇（10当量）。 （二），得到纯化后参照的分离产率。从参考24修改。 值得注意的是反应是极其立体选择性，并且仅获得的抗-diastereoisomer。 反取向连位二苯基物用化合物3（图3）的X射线分析测定。 <html> JPG"/&gt; 图3:3的酮酯的ORTEP绘图与许可参考24重新打印。 如示出的纯酮酯1可以简单的后处理和洗涤之后协议来获得。白细胞介素然后可以在甲醇溶液蒸发后回收。白细胞介素已被再循环至五倍，在反应产率没有降低。24 此外，1,6-酮酯也是有效的胶凝剂中的烃溶剂如己烷和庚烷（ 图4）。29胶凝是浓度依赖性的，酮酯1凝胶化已经以2mg / ml的10分钟内的浓度。在较高浓度的凝胶化发生分钟内。凝胶化是可逆的，并且加入二氯甲烷或加热将重新溶解的酮酯。 ig4.jpg"/&gt; 图4:凝胶在庚烷（a和b）的有机凝胶胶凝剂1的庚烷（5毫克/毫升）。从烧杯中（三）凝胶除去。

Watch this Scientific Journal Video about Highly Stereoselective Synthesis of 1,6-Ketoesters Mediated by Ionic Liquids: A Three-component Reaction Enabling Rapid Access to a New Class of Low Molecular

Highly Stereoselective Synthesis of 1,6-Ketoesters Mediated by Ionic Liquids: A Three-component Reaction Enabling Rapid Access to a New Class of Low Molecular Weight Gelators

Ionic liquids (ILs) mediate fast, simple and cheap access to 1,6-ketoesters in high diastereoselectivities and good yields. The reaction protocol is robust and the 1,6-ketoesters can be obtained in gram scale after a simple filtration protocol. Moreover, the 1,6-ketoesters are potent gelators in hydrocarbon solvents.

1,6-酮酯高立体选择性合成离子液体介导:三组分反应启用快速进入低分子量胶凝剂的新型类

In organic chemistry ionic liquids (ILs) have emerged as safe and recyclable reaction solvents. In the presence of a base ILs can be deprotonated to form ...

highly-stereoselective-synthesis-16-ketoesters-mediated-ionic-liquids

Nanyang Technological University

Research

JoVE Journal

Chemistry

9.6K 次观看.  Chalmers University of Technology. Ionic liquids (ILs) mediate fast, simple and cheap access to 1,6-ketoesters in high diastereoselectivities and good yields. The reaction protocol is robust and the 1,6-ketoesters can be obtained in gram scale after a simple filtration protocol. Moreover, the 1,6-ketoesters are potent gelators in hydrocarbon solvents. 

视频: Highly Stereoselective Synthesis of 1,6-Ketoesters Mediated by Ionic Liquids: A Three-component Reaction Enabling Rapid Access to a New Class of Low Molecular Weight Gelators

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine

Amino alcohols are versatile compounds with a wide range of applications. For instance, they have been used as chiral scaffolds in organic synthesis. Their synthesis by conventional organic chemistry often requires tedious multi-step synthesis processes, with difficult control of the stereochemical outcome. We present a protocol to enzymatically synthetize amino alcohols starting from the readily available L-lysine in 48 h. This protocol combines two chemical reactions that are very difficult to conduct by conventional organic synthesis. In the first step, the regio- and diastereoselective oxidation of an unactivated C-H bond of the lysine side-chain is catalyzed by a dioxygenase; a second regio- and diastereoselective oxidation catalyzed by a regiodivergent dioxygenase can lead to the formation of the 1,2-diols. In the last step, the carboxylic group of the alpha amino acid is cleaved by a pyridoxal-phosphate (PLP) decarboxylase (DC). This decarboxylative step only affects the alpha carbon of the amino acid, retaining the hydroxy-substituted stereogenic center in a beta/gamma position. The resulting amino alcohols are therefore optically enriched. The protocol was successfully applied to the semipreparative-scale synthesis of four amino alcohols. Monitoring of the reactions was conducted by high performance liquid chromatography (HPLC) after derivatization by 1-fluoro-2,4-dinitrobenzene. Straightforward purification by solid-phase extraction (SPE) afforded the amino alcohols with excellent yields (93% to &#62;95%).

Chiral amino alcohols are versatile molecules for use as scaffolds in organic synthesis. Starting from L-lysine, we synthesize amino alcohols by an enzymatic cascade reaction combining diastereoselective C-H oxidation catalyzed by dioxygenase followed by cleavage of the carboxylic acid moiety of the corresponding hydroxyl amino acid by a decarboxylase.

酶联反应合成 l-赖氨酸手性氨基醇的研究

Amino alcohols are versatile compounds with a wide range of applications. For instance, they have been used as chiral scaffolds in organic synthesis. ...

科研

化学

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 ...

Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile

The Steglich esterification is a widely-used reaction for the synthesis of esters from carboxylic acids and alcohols. While efficient and mild, the reaction is commonly performed using chlorinated or amide solvent systems, which are hazardous to human health and the environment. Our methodology utilizes acetonitrile as a greener and less hazardous solvent system. This protocol exhibits rates and yields that are comparable to traditional solvent systems and employs an extraction and wash sequence that eliminates the need for the purification of the ester product via column chromatography. This general method can be used to couple a variety of carboxylic acids with 1&#176; and 2&#176; aliphatic alcohols, benzylic and allylic alcohols, and phenols to obtain pure esters in high yields. The goal of the protocol detailed here is to provide a greener alternative to a common esterification reaction, which could serve useful for ester synthesis in both academic and industrial applications.

A modified Steglich esterification reaction was used to synthesize a small library of ester derivatives with primary and secondary alcohols. The methodology uses a non-halogenated and greener solvent, acetonitrile, and enables product isolation in high yields without the need for chromatographic purification.

乙腈绿色 Steglich 酯化合成酯的研究

The Steglich esterification is a widely-used reaction for the synthesis of esters from carboxylic acids and alcohols. While efficient and mild, the ...

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of &#945;-Imino &#947;-Lactones and Alkylidene Pyrazolones

Bispirocyclic scaffolds are one of the important structural subunits in many natural products that exhibit diverse and attractive biological activities. Recently, we have developed an efficient organocatalytic strategy, which provides facile access to a variety of enantiomerically enriched bispiro[&#947;-butyrolactone-pyrrolidin-4,4&#39;-pyrazolone] skeletons. In this paper, we demonstrate a detailed protocol for the asymmetric synthesis of drug-like bispirocyclic compounds with two spirocyclic carbon centers via an organocatyltic 1,3-dipolar cycloaddition reaction. Spirocyclization synthons &#945;-imino &#947;-lactones and alkylidene pyrazolones are prepared first, which are then subjected to a cycloaddition reaction in the presence of a bifunctional squaramide organocatalyst to afford the desired bispirocycles in high yields and excellent stereoselectivities. Chiral high-performance liquid chromatography (HPLC) is carried out to determine the enantiomeric purity of the products, and the d.r. value is examined by proton nuclear magnetic resonance (1H NMR). The absolute configuration of the product is assigned according to an X-ray crystallographic analysis. This synthetic strategy allows scientists to prepare a diversity of bispirocyclic scaffolds in high yields and excellent diastereo- and enantioselectivities.

Enantiomerically enriched bispiro[&#947;-butyrolactone-pyrrolidin-4,4&#39;-pyrazolone] skeletons are asymmetrically synthesized through a simple organocatalytic 1,3-dipolar cycloaddition reaction.

α-伊米诺γ-乳胶酮和阿基地利酮吡唑酮有机催化环加花法高效构建药物样双环脚手架

Bispirocyclic scaffolds are one of the important structural subunits in many natural products that exhibit diverse and attractive biological activities. ...

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 ...

Versatile CO2 Transformations into Complex Products: A One-pot Two-step Strategy

CO2 transformations using a one-pot two-step method are presented herein. The purpose of the method is to give access to a variety of value-added products and notably to generate chiral carbon centers. The crucial first step consists in the selective double hydroboration of CO2 catalyzed by an iron hydride complex. The product obtained with this 4 e- reduction is a rare bis(boryl)acetal, compound 1, which is subjected in situ to three different reactions in a second step. The first reaction concerns a condensation reaction with (diisopropyl)phenylamine affording the corresponding imine 2. In the second and third reaction, intermediate 1 reacts with triazol-5-ylidene (Enders&#39; carbene) to afford compounds 3 or 4, depending on the reaction conditions. In both compounds, C-C bonds are formed, and chiral centers are generated from CO2 as the only source of carbon. Compound 4 exhibits two chiral centers obtained in a diastereoselective manner in a formose-type mechanism. We proved that the remaining boryl fragment plays a key role in this unprecedented stereocontrol. The interest of the method stands on the reactive and versatile nature of 1, giving rise to various complex molecules from a single intermediate. The complexity of a two-step method is compensated by the overall short reaction time (2 h for the larger reaction time), and mild reaction conditions (25 &#176;C to 80 &#176;C and 1 to 3 atm of CO2).

Versatile CO2 Transformations into Complex Products: A One-pot Two-step Strategy

CO2 transformations are conducted in a one-pot two-step procedure for the synthesis of complex molecules. The selective 4 e- reduction of CO2 with a hydroborane reductant affords a reactive and versatile bis(boryl)acetal intermediate which is subsequently involved in condensation reaction or carbene-mediated C-C coupling generation.

多功能 CO2转化为复杂产品:单罐两步战略

CO2 transformations using a one-pot two-step method are presented herein. The purpose of the method is to give access to a variety of value-added products ...

Organocatalysis

Source: Vy M. Dong and Faben Cruz, Department of Chemistry, University of California, Irvine, CA
This experiment will demonstrate the concept of organocatalysis by illustrating the proper setup of a reaction that utilizes enamine catalysis. Organocatalysis is a form of catalysis that uses substoichiometric amounts of small organic molecules to accelerate reactions. This type of catalysis is complementary to other forms of catalysis such as transition metal or biocatalysis. Transition metal catalysis involves transition metals as catalysts and biocatalysis uses enzymes as catalysts. Some advantages of organocatalysis include the low toxicity and cost of the organocatalysts in comparison to many metal catalysts. In addition, most organocatalysts are not sensitive to air and moisture, unlike metal catalysts. In contrast to enzymes found in living organisms, the small molecules that act as organocatalysts are typically easy to access. Furthermore, organocatalysis offers complementary and new reactivity not observed with other forms of catalysis.

Organocatalysis: Principles and Applications

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Source: Vy M. Dong and Faben Cruz, Department of Chemistry, University of California, Irvine, CA
This experiment will demonstrate the concept of ...

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JoVE Science Education

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&alpha;-Alkylation of Ketones via Enolate Ions

Ketones with &#945; protons are deprotonated by strong bases like lithium diisopropylamide (LDA) to form enolate ions. The anion is stabilized by resonance, and its hybrid structure exhibits negative charges on the carbonyl oxygen and the &#945; carbon. This ambident nucleophile can attack an electrophile via two possible sites: the carbonyl oxygen, known as O-attack, or the &#945;&nbsp;carbon, known as C-attack. The nucleophilic attack via the carbanionic site is preferred. This is due to the strong interaction of the positive counterpart of the base with the anionic oxygen, which restricts the approaching electrophile, making the reaction less favorable. Also, the product obtained through C-attack is more stable than that obtained through O-attack, as the stronger C=O &#960; bond is retained in the former, whereas a weaker C=C &#960; bond is preserved in the latter.
A subsequent reaction of the enolate with electrophiles such as alkyl halides produces an &#945;-alkylated ketone via the SN2 pathway. The &#945;-alkylation of ketones is achieved with the halides of primary alkyl, benzyl, and allylic groups. With secondary and tertiary alkyl halides, elimination predominates over substitution.