ethyl 2-(p-methoxyphenylamino)-3-hydroxy-4-oxo-pentanoate

• 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: ethyl 2-(p-methoxyphenylamino)-3-hydroxy-4-oxo-pentanoate
• 英文别名: Ethyl 3-hydroxy-2-(4-methoxyanilino)-4-oxopentanoate；ethyl 3-hydroxy-2-(4-methoxyanilino)-4-oxopentanoate
• 化学式: C₁₄H₁₉NO₅
• 分子量: 281.309
• InChiKey: ZFMWDSYOJJEUIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  Acetic acid, [(4-methoxyphenyl)imino]-, ethyl ester, (2E)- 、 羟基丙酮 在 L-脯氨酸 作用下， 以 二甲基亚砜 为溶剂， 生成 ethyl 2-(p-methoxyphenylamino)-3-hydroxy-4-oxo-pentanoate 、 ethyl (2S,3S)-2-(4-methoxy-phenylamino)-3-hydroxy-4-oxo-pentanoate
  参考文献：
  名称：

  一种高度对映选择性氨基酸催化的功能化α-氨基酸途径

  摘要：

  提供对映异构纯 α-氨基酸的合成方法的发展引起了几代化学家的兴趣，并成为深入研究的主题。本报告描述了基于催化不对称合成的功能化 α-氨基酸的一般方法。脯氨酸催化 N-PMP 保护的 α-亚氨基乙醛酸乙酯与各种未修饰的酮的曼尼希型反应，以高产率提供功能化的 α-氨基酸，具有出色的区域选择性、非对映选择性和对映选择性。对七个实例的研究产生了六个，产品 ee 值≥99%。在涉及可以形成非对映异构产物的酮供体的反应中，两个相邻的立体中心在碳-碳键形成时同时产生，具有完全的同步立体控制。显着地，

  DOI：

  10.1021/ja017270h

文献信息

• A Highly Enantioselective Amino Acid-Catalyzed Route to Functionalized α-Amino Acids
  作者：Armando Córdova、Wolfgang Notz、Guofu Zhong、Juan M. Betancort、Carlos F. Barbas

  DOI：10.1021/ja017270h

  日期：2002.3.1

  enantiomerically pure α-amino acids has intrigued generations of chemists and been the subject of intense research. This report describes a general approach to functionalized α-amino acids based on catalytic asymmetric synthesis. Proline catalyzed Mannich-type reactions of N-PMP-protected α-imino ethyl glyoxylate with a variety of unmodified ketones to provide functionalized α-amino acids in high yields with

  提供对映异构纯 α-氨基酸的合成方法的发展引起了几代化学家的兴趣，并成为深入研究的主题。本报告描述了基于催化不对称合成的功能化 α-氨基酸的一般方法。脯氨酸催化 N-PMP 保护的 α-亚氨基乙醛酸乙酯与各种未修饰的酮的曼尼希型反应，以高产率提供功能化的 α-氨基酸，具有出色的区域选择性、非对映选择性和对映选择性。对七个实例的研究产生了六个，产品 ee 值≥99%。在涉及可以形成非对映异构产物的酮供体的反应中，两个相邻的立体中心在碳-碳键形成时同时产生，具有完全的同步立体控制。显着地，
• Direct Catalytic Asymmetric Synthesis of <i>anti</i>-1,2-Amino Alcohols and <i>syn</i>-1,2-Diols through Organocatalytic <i>anti</i>-Mannich and <i>syn</i>-Aldol Reactions
  作者：S. S. V. Ramasastry、Haile Zhang、Fujie Tanaka、Carlos F. Barbas

  DOI：10.1021/ja0677012

  日期：2007.1.1

  anti-1,2-amino alcohols and syn-1,2-diols through direct asymmetric Mannich, Mannich-type, and aldol reactions involving unmodified α-hydroxyketones in reactions catalyzed by primary amine-containing amino acids. These reactions exploit (Z)-enamines of α-hydroxyketones in their bond-forming transition states. This study compliments and extends our bioorganic approach to asymmetric synthesis in these two

  手性 1,2-氨基醇和 1,2-二醇是在大量天然和生物活性分子中发现的常见结构基序。已经报道了使用基于金属的策略有效对映选择性合成含有顺-或反-1,2-氨基醇和1,2-二醇的酮。然而，迄今为止，涉及有机催化的方法仅限于合成 1,2-氨基醇和反 1,2-二醇。在此，我们公开了通过直接不对称曼尼希、曼尼希型和羟醛反应（涉及未修饰的 α-羟基酮在伯胺催化的反应中）制备高度对映体富集的抗 1,2-氨基醇和合成 1,2-二醇的简单有效途径-含氨基酸。这些反应利用处于成键过渡态的 α-羟基酮的 (Z)-烯胺。这项研究补充并扩展了我们在这两种多功能合成子类中进行不对称合成的生物有机方法。值得注意的是，这些反应是实用的，耐受湿溶剂，并且...
• Catalysis of 3-Pyrrolidinecarboxylic Acid and Related Pyrrolidine Derivatives in Enantioselective <i>anti</i>-Mannich-Type Reactions:  Importance of the 3-Acid Group on Pyrrolidine for Stereocontrol
  作者：Haile Zhang、Susumu Mitsumori、Naoto Utsumi、Masanori Imai、Noemi Garcia-Delgado、Maria Mifsud、Klaus Albertshofer、Paul Ha-Yeon Cheong、K. N. Houk、Fujie Tanaka、Carlos F. Barbas

  DOI：10.1021/ja074907+

  日期：2008.1.1

  The development of enantioselective anti-selective Mannich-type reactions of aldehydes and ketones with imines catalyzed by 3-pyrrolidinecarboxylic acid and related pyrrolidine derivatives is reported in detail. Both (3R,5R)-5-methyl-3-pyrrolidinecarboxylic acid and (R)-3-pyrrolidinecarboxylic acid efficiently catalyzed the reactions of aldehydes with alpha-imino esters under mild conditions and afforded anti-Mannich products with high diastereo- and enantioselectivities (anti/syn up to 99:1, up to >99% ee). For the reactions of ketones with a-imino esters, (R)-3-pyrrolidinecarboxylic acid was an efficient catalyst (anti/syn up to >99:1, up to 99% ee). Evaluation of a series of pyrrolidine-based catalysts indicated that the acid group at the beta-position of the pyrrolidine ring of the catalyst played an important role in forwarding the carbon-carbon bond formation and in directing anti-selectivity and enantioselectivity.
• Continuous Flow Enantioselective Three-Component <i>anti</i>-Mannich Reactions Catalyzed by a Polymer-Supported Threonine Derivative
  作者：Carles Ayats、Andrea H. Henseler、Estefanía Dibello、Miquel A. Pericàs

  DOI：10.1021/cs5006037

  日期：2014.9.5

  A series of primary amino acid-derived polystyrene-supported organocatalysts was tested in antiselective Mannidi reactions. The polystyrene-immobilized threonine derivative showed the best performance in threecomponent (hydroxyacetone, anilines, and aldehydes) Mannich reactions to provide anti-beta-amino-alpha-hydroxycarbonyl compounds (11 examples; up to 95% ee), and its use could be extended to dihydroxyacetone and protected hydroxyace-tones (7 examples; up to 90% ee). The high activity depicted by the catalyst has allowed its implementation in continuous flow. Under this operation mode, the supported threonine catalyst produces anti-Mannich adducts with generally higher diastereo- and enantioselectivity than in batch. A family of five different enantioenriched anti-Mannich adducts has been sequentially prepared in flow by passing different combinations of anilines and aromatic aldehydes over the same sample of catalyst. This confirms the suitability of this methodology for the rapid access to small libraries of enantioenriched compounds.
• Insights into the spontaneous emergence of enantioselectivity in an asymmetric Mannich reaction carried out without external catalyst
  作者：Felix E. Held、Anja Fingerhut、Svetlana B. Tsogoeva

  DOI：10.1016/j.tetasy.2012.10.021

  日期：2012.12

  ESI-MS, chiral HPLC, time-resolved H-1 NMR and optical rotation measurements were performed to gain insights into the nature of spontaneous mirror symmetry breaking in the catalyst-free Mannich reaction of PMP protected alpha-iminoethylglyoxylate with hydroxyacetone. Spontaneous temporary generation of enantiomeric excesses of up to 7.4% in the major syn diastereomer is reproducibly observed in aqueous phosphate buffers, starting from achiral conditions. The syn-product ee values for both enantiomers [(2S,3S) and (2R,3R)], although not with stochastic distribution, have been observed with no clear preference for either enantiomer. (C) 2012 Elsevier Ltd. All rights reserved.