(R)-ethyl 2-[(4-methoxyphenyl)amino]-2-[(S)-4-oxotetrahydro-2H-pyran-3-yl]acetate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-ethyl 2-[(4-methoxyphenyl)amino]-2-[(S)-4-oxotetrahydro-2H-pyran-3-yl]acetate
• 英文别名: ethyl (2R,3S)-2-(4-methoxy-phenylamino)-2-(4-oxo-tetrahydro-pyran-3-yl)-acetate；ethyl (2R)-2-(4-methoxyanilino)-2-[(3S)-4-oxooxan-3-yl]acetate
• 化学式: C₁₆H₂₁NO₅
• 分子量: 307.346
• InChiKey: VDHDJWMNQOFGMW-DZGCQCFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  甲氧苯胺 、 alkaline earth salt of/the/ methylsulfuric acid 在 (S)-2-(trifluoromethane-sulfonylamino-methyl)-pyrrolidine 4 A molecular sieve 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 16.0h， 生成 (R)-ethyl 2-[(4-methoxyphenyl)amino]-2-[(S)-4-oxotetrahydro-2H-pyran-3-yl]acetate
  参考文献：
  名称：

  Catalysis of highly stereoselective Mannich-type reactions of ketones with α-imino esters by a pyrrolidine-sulfonamide. Synthesis of unnatural α-amino acids

  摘要：

  The novel pyrrolidine-sulfonamide I has been prepared and used successfully to catalyze Mannich-type reactions between ketones and alpha-imino esters. The process is used to efficiently synthesize functionalized alpha-amino acid derivatives with excellent levels of regio-, diastereo-, and enantio-selectivity. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2004.08.032

文献信息

• TRANS-3,5-DISUBSTITUTEDPYRROLIDINE: ORGANOCATALYST FOR anti-MANNICH REACTIONS
  申请人：Tanaka Fujie

  公开号：US20070117986A1

  公开（公告）日：2007-05-24

  A compound of Formula I is disclosed, in which R is a substituent containing a hydrogen bond-forming atom within three atoms from the ring carbon to which the substituent is bonded; X is CH 2 , O, S or NR 1 , wherein R 1 is a hydrocarbyl group or an amino-protecting group having one to about 18 carbon atoms; R 2 is hydrido or a hydrocarbyl group containing one to about twelve carbon atoms; and R 3 is hydrido or methyl, but both R 2 and R 3 are not hydrido when X is CH 2 A molecule of Formula I and those in which R 2 and R 3 can both be hydrido (Formula X) functions as a catalyst in a Mannich reaction to asymmetrically form β-aminoaldehyde or β-aminoketone diastereomeric products having two chiral centers on adjacent carbon atoms and in which the anti-diastereomers are in excess over the syn-diastereomers. Methods for carrying out those syntheses are also disclosed.

  披露了一种公式I的化合物，其中R是含有一个在距离与亚基连接的环碳三个原子以内的氢键形成原子的取代基；X是CH2，O，S或NR1，其中R1是一个含有一个到约18个碳原子的烃基团或一个氨基保护基团；R2是氢化物或含有一个到约十二个碳原子的烃基团；R3是氢化物或甲基，但是当X是 时，R2和R3不能都是氢化物。公式I的分子以及其中R2和R3都可以是氢化物（公式X）的分子，在曼尼希反应中作为催化剂，非对称地形成具有相邻碳原子上的两个手性中心的β-氨基醛或β-氨基酮对映异构体产品，并且反式对映异构体过剩于顺式对映异构体。还披露了进行那些合成的方法。
• A Solid-Supported Organocatalyst for Highly Stereoselective, Batch, and Continuous-Flow Mannich Reactions
  作者：Esther Alza、Carles Rodríguez-Escrich、Sonia Sayalero、Amaia Bastero、Miquel A. Pericàs

  DOI：10.1002/chem.200901310

  日期：2009.10.5

  fast reactions leading to complete conversion in 1–3 h are recorded in DMF. With ketone donors, the reactions tend to be slower, but can be efficiently accelerated (six‐membered ring cycloalkanones) by low‐power microwave irradiation. This approach, which greatly facilitates product isolation since the catalyst is removed by simple filtration, has allowed the implementation of the reactions of aldehyde

  据报道，在（2 S，4 R）-羟基脯氨酸官能化的聚苯乙烯树脂的催化下，醛和酮与N-（对-甲氧基苯基）乙醛酸乙酯亚胺的快速，高度立体选择性曼尼希反应。已经研究了脯氨酸与聚合物主链连接的接头性质的影响，并且由叠氮基甲基聚苯乙烯和O构成了1,2,3-三唑接头事实证明，炔丙基羟基脯氨酸是催化活性和对映选择性的最佳选择。对于醛供体，在DMF中记录了可在1-3小时内完成完全转化的快速反应。使用酮供体，反应往往较慢，但可以通过低功率微波辐射有效地加速（六元环环烷酮）。这种方法极大地促进了产物的分离，因为通过简单的过滤就可以除去催化剂，从而可以在连续流，单程系统中实施醛底物的反应。以这种方式，连续合成对映体和非对映体纯加合物（syn / anti > 97：3; ee在室温下，停留时间为6.0分钟，已达到> 99％）。该方法通过大大简化的实验规程避免了纯化步骤，从而通过使用0.46 mmol的催化树脂（5
• An Efficient Route to Quinolines and Other Compounds by Iron-Catalysed Cross-Dehydrogenative Coupling Reactions of Glycine Derivatives
  作者：Peng Liu、Zhiming Wang、Jue Lin、Xianming Hu

  DOI：10.1002/ejoc.201101656

  日期：2012.3

  A simple method has been developed for functionalizing glycine derivatives by iron-catalysed cross-dehydrogenative coupling (CDC) reactions. In particular, N-arylglycine derivatives reacted with alkynes by oxidative C–H/C–H coupling reactions to provide a series of substituted quinolines starting from commercially inexpensive materials. Moreover, N-arylglycine esters can be oxidatively coupled to ketones

  已经开发出一种通过铁催化的交叉脱氢偶联 (CDC) 反应功能化甘氨酸衍生物的简单方法。特别是，N-芳基甘氨酸衍生物通过氧化 C-H/C-H 偶联反应与炔烃反应，从商业上廉价的材料开始提供一系列取代的喹啉。此外，N-芳基甘氨酸酯可以通过在 DDQ 存在下使用 FeCl3 氧化偶联到酮上。
• List–Barbas–Mannich Reaction Catalyzed by Modularly Designed Organocatalysts
  作者：Sandun Perera、Debarshi Sinha、Nirmal K. Rana、Van Trieu-Do、John Cong-Gui Zhao

  DOI：10.1021/jo4019304

  日期：2013.11.1

  The List-Barbas-Mannich reaction of ethyl (p-methoxyphenylimino)acetate (p-methoxyphenyl = PMP) with unmodified aldehydes or ketones catalyzed by modularly designed organocatalysts (MDOs) that are self-assembled from proline and cinchona alkaloid thioureas (such as a quinidine-derived thiourea) produces the corresponding gamma-oxo-alpha-amino acid derivatives in high yields and excellent stereoselectivities. No solvent is necessary for this reaction. Aldehydes are especially good substrates for this reaction: The reaction takes only a few minutes to yield the corresponding List-Barbas-Mannich products in excellent dr (up to >99:1) and ee values (up to >99% ee).