2-(hydroxy(pyridin-4-yl)methyl)cyclohexanone | 457053-28-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-(hydroxy(pyridin-4-yl)methyl)cyclohexanone
• 英文别名: 2-[hydroxy-(pyridine-4-yl)methyl]-cyclohexanone；2-(hydroxyl-(p-pyridin)methyl)cyclohexan-1-one；2-[hydroxyl(pyridin-4-yl)methyl]cyclohexanone；(2RS)-2-[(RS)-hydroxy-(pyridin-4-yl)methyl]cyclohexan-1-one；2-[hydroxy(pyridine-4-yl)methyl]cyclohexan-1-one；2-[hydroxy(pyridin-4-yl)methyl]cyclohexan-1-one
• CAS: 457053-28-0
• 化学式: C₁₂H₁₅NO₂
• 分子量: 205.257
• InChiKey: XMRRGLWNAQVZMK-UHFFFAOYSA-N

物化性质

• 沸点：
  392.4±17.0 °C(Predicted)
• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(hydroxy(pyridin-4-yl)methyl)cyclohexanone 在 三氟甲磺酸三甲基硅酯 、 乙酸酐 、 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 异丙醇 、 乙腈 为溶剂， 反应 10.75h， 生成 (3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(6R)-2-{(E)-(pyrid-4-yl)methylene}-1-oxocyclohex-6-yl]azetidin-2-one
  参考文献：
  名称：

  Preparation of the Key Intermediate in the Synthesis of GV143253A:  The Anti-MRSA/E Injectable Trinem

  摘要：

  GV143253A is a broad-spectrum injectable beta-lactam belonging to the class of trinem antibiotics. A key intermediate (3S,4R)-3-[(1R)-1-(tert-butyldimethyl- silyloxy)ethyl]-4-[-(6'R)-2'-[(E)(pyrid-4yl)methylene]-1'-oxocyclohex-6'-yl]azetidin-2-one (10) was identified and synthesized via different enolate coupling approaches, using enol ether, lithium, sodium, magnesium, tin, zinc, zirconium, and titanium enolates. Among these approaches, the synthesis of (3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[-(6'R)-2'-[(E)-(pyrid-4yl)-methylene]-1'-oxo- cyclohex-6'-yl]azetidin-2-one (10) via a titanium enolate offered advantages in terms of greater diastereoselectivity, higher yield, robustness, and isolation of intermediates and was superior to the method previously used for preparing large quantities of drug substance for early development studies.

  DOI：

  10.1021/op020024l
• 作为产物：
  描述：

  环己酮 、 4-吡啶甲醇 在 sodium anthraquinone-2-sulfonate 、 溶剂黄146 、 反-4-(叔丁基二苯基硅氧基)-L-脯氨酸 作用下， 以 水 为溶剂， 反应 48.0h， 以7%的产率得到2-(hydroxy(pyridin-4-yl)methyl)cyclohexanone
  参考文献：
  名称：

  以水为溶剂的苄醇的需氧光氧化直接不对称醛醇缩合反应†

  摘要：

  我们报告了使用水为溶剂的需氧光氧化直接不对称羟醛反应。在该反应中，使用蒽醌-2-磺酸钠一水合物作为有机光催化剂，在氧气气氛下，伯苄醇被氧化为苯甲醛。然后使用脯氨酸型有机催化剂进行立体选择性醛醇缩合反应。

  DOI：

  10.1039/c5ra05155j

文献信息

• Prolinamides of Aminouracils, Organocatalyst Modifiable by Complementary Modules
  作者：Karen M. Ruíz-Pérez、Beatriz Quiroz-García、Marcos Hernández-Rodríguez

  DOI：10.1002/ejoc.201800886

  日期：2018.11.8

  Prolinamide organocatalysts with aminouracils have the features of enhanced NH acidity, an additional hydrogen‐bond donor and the self‐assembly with complementary modules by Watson–Crick pairing. Each module affects the selectivity of the reaction and particularly 2,6‐diaminopyridine is beneficial to the selectivity in the reaction.

  带有氨基尿嘧啶的脯氨酰胺有机催化剂具有增强的NH酸度，额外的氢键供体以及通过沃森-克里克配对与互补模块自组装的特点。每个模块都会影响反应的选择性，特别是2,6-二氨基吡啶对反应的选择性有益。
• Proline dipeptides containing fluorine moieties as oganocatalysts for the asymmetric aldol reaction
  作者：Ardiol Ahmetlli、Nikoleta Spiliopoulou、Angeliki Magi-Oikonomopoulou、Dimitrios-Triantaffylos Gerokonstantis、Panagiota Moutevelis-Minakakis、Christoforos G. Kokotos

  DOI：10.1016/j.tet.2018.08.038

  日期：2018.10

  demonstrated, where aromatic aldehydes afforded products in high yields (up to 100%) with excellent diastereo- (up to 95:5) and enantioselectivities (up to 97%), whereas the aliphatic aldehydes afforded also excellent selectivities, but relatively low yield. A simple addition of fluorine to a dipeptide analogue affords organocatalysts with new interesting properties that can catalyze the aldol reaction

  合成了由脯氨酸，苯丙氨酸和苯胺-或苯酚-氟衍生物组成的一系列二肽类似物。在分子间不对称醛醇缩合反应中，在有机介质和水性介质中均评估了它们的催化能力。当2-CF 3时，苯胺-氟衍生物被证明是优越的，并获得了最佳结果。使用了苯胺。证明了由芳香族和脂肪族醛以及不同的酮组成的多种底物范围，其中芳香族醛提供高收率（高达100％）的产品，具有出色的非对映异构性（高达95：5）和对映选择性（高达90％）。 97％），而脂族醛也提供了优异的选择性，但是产率相对较低。将氟简单地添加到二肽类似物中可以提供具有新的有趣特性的有机催化剂，该特性可以更有效地催化羟醛反应。
• SULFONAMIDE-BASED ORGANOCATALYSTS AND METHOD FOR THEIR USE
  申请人：Carter Rich Garrett

  公开号：US20100184986A1

  公开（公告）日：2010-07-22

  Organocatalysts, particularly proline sulfonamide organocatalysts, having a first general formula as follows are disclosed. Embodiments of a method for using these organocatalysts also are disclosed. The method comprises providing a disclosed organocatalyst, and performing a reaction, often an enantioselective or diastereoselective reaction, using the organocatalyst. Solely by way of example, disclosed catalysts can be used to perform aldol reactions, conjugate additions, Michael additions, Robinson annulations, Mannich reactions, α-aminooxylations, α-hydroxyaminations, α-aminations and alkylation reactions. Certain of such reactions are intramolecular cyclizations used to form cyclic compounds, such as 5- or 6-membered rings, having one or more chiral centers. Disclosed organocatalysts generally are much more soluble in typical solvents used for organic synthesis than are known compounds. Moreover, the reaction yield is generally quite good with disclosed compounds, as is their enantioselective and diastereoselective effectiveness.

  披露了具有如下一般公式之一的有机催化剂，尤其是脯氨酸磺酰胺有机催化剂。还披露了使用这些有机催化剂的方法的实施例。该方法包括提供一种披露的有机催化剂，并使用该有机催化剂进行反应，通常是立体选择性的反应或对映选择性反应。仅作为示例，披露的催化剂可用于进行aldol反应、共轭加成、Michael加成、Robinson环化反应、Mannich反应、α-氨基氧化、α-羟基胺化、α-胺化和烷基化反应。其中一些反应是分子内环化反应，用于形成具有一个或多个手性中心的环状化合物，例如5或6元环。披露的有机催化剂通常比已知的化合物更容易溶于用于有机合成的典型溶剂中。此外，使用披露化合物的反应收率通常相当好，它们的对映选择性和非对映选择性效果也很好。
• Novel Axially Unfixed Biaryl-Based Water-Compatible Organocatalysts: Design, Synthesis and Their Asymmetric Catalysis in Direct Aldol Reactions in Water
  作者：Hong-Wu Zhao、Yuan-Yuan Yue、Hai-Long Li、Xiu-Qing Song、Zhi-Hui Sheng、Zhao Yang、Wei Meng、Ze Yang

  DOI：10.1055/s-0033-1339497

  日期：——

  A family of novel axially unfixed biaryl-based, water-compatible bifunctional organocatalysts were designed and synthesized for asymmetric catalytic direct aldol reactions in water. These organocatalysts are comprised of prolinamide, aromatic sulfonamide and biaryl motifs. Under the optimal reaction conditions, one organocatalyst in particular delivered excellent stereocontrol (up to 99% ee and 99:1

  设计并合成了一系列新型轴向未固定联芳基、水相容的双功能有机催化剂，用于在水中进行不对称催化直接醛醇反应。这些有机催化剂由脯氨酰胺、芳族磺酰胺和联芳基基序组成。在最佳反应条件下，特别是一种有机催化剂在环己酮与水中多种芳香醛的直接醛醇反应中提供了出色的立体控制（高达 99% ee 和 99:1 dr）。
• Dipeptide-catalyzed direct asymmetric aldol reactions in the presence of water
  作者：Meng Lei、Lanxiang Shi、Gong Li、Shilv Chen、Weihai Fang、Zemei Ge、Tieming Cheng、Runtao Li

  DOI：10.1016/j.tet.2007.05.077

  日期：2007.8

  dipeptide has been discovered and developed as an efficient catalyst for the direct asymmetric aldol reactions of unmodified ketones with various aldehydes including aromatic, aliphatic, heteroaromatic, and unsaturated aldehydes in the presence of water at 0 °C. The resulted methodology and optimal conditions led to the corresponding aldol products with high yields (up to 94%) and good enantioselectivities

  基于l-脯氨酸的二肽已被发现并开发为在0°C的水存在下，未修饰的酮与各种醛（包括芳族，脂肪族，杂芳族和不饱和醛）直接不对称醛醇缩合反应的有效催化剂。所得到的方法学和最佳条件导致相应的醛醇产物具有高产率（高达94％）和良好的对映选择性（高达97％ee）。