(S)-ethyl 2-[(4-methoxyphenyl)amino]-2-[(R)-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: (S)-ethyl 2-[(4-methoxyphenyl)amino]-2-[(R)-4-oxotetrahydro-2H-pyran-3-yl]acetate
• 英文别名: ethyl (2S,3R)-2-(4-methoxy-phenylamino)-2-(4-oxo-tetrahydro-pyran-3-yl)-acetate；(2S,3S)-ethyl-2-(p-methoxyphenylamino)-2-(4'-oxotetrahydropyran-3'-yl)acetate；ethyl (2S,1'S)-2-(p-methoxyphenylamino)-2-(6'-oxo-3'-oxan-1'-yl)acetate；ethyl (2S)-2-(4-methoxyanilino)-2-[(3R)-4-oxooxan-3-yl]acetate
• 化学式: C₁₆H₂₁NO₅
• 分子量: 307.346
• InChiKey: VDHDJWMNQOFGMW-HIFRSBDPSA-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：

  四氢吡喃酮 、 Acetic acid, [(4-methoxyphenyl)imino]-, ethyl ester, (2E)- 在 N-[(2S)-2-吡咯烷甲基]-三氟甲磺酰胺 作用下， 以 二甲基亚砜 为溶剂， 反应 9.0h， 以83%的产率得到(S)-ethyl 2-[(4-methoxyphenyl)amino]-2-[(R)-4-oxotetrahydro-2H-pyran-3-yl]acetate
  参考文献：
  名称：

  [EN] ORGANOCATALYSTS AND METHODS OF USE IN CHEMICAL SYNTHESIS
  [FR] ORGANOCATALYSEURS ET PROCEDES D'UTILISATION DE CES DERNIERS DANS LA SYNTHESE CHIMIQUE

  摘要：

  本发明涉及一般包括有机催化剂的组合物，该催化剂促进立体选择性反应以及其合成和使用方法。特别地，本发明涉及无金属有机催化剂以促进立体选择性反应，以及其合成和使用方法。这些化合物具有以下结构的式（I）和（II）。其中X独立地选择自CH2、N-Ra、O、S或C=O；Y为CH2、N-Ra、O、S或C=O，但至少X或Y中的一个为CH2，最好是X和Y都为CH2；Ra为H、可选择地取代的C1-C12烷基，最好是可选择地取代的C1-C6烷基，包括C3-C6环烷基，或可选择地取代的芳基，最好是可选择地取代的苯基；Rb为H、可选择地取代的C1-C12烷基，最好是可选择地取代的C1-C6无环或C3-C6环烷基，CHO、N(Me)O、CO(S)Ra或式（III）的基团。其中Rc和Rd各自独立地为H、F、C1、可选择地取代的C1-C20烷基，最好是可选择地取代的C1-C12烷基，更好地是C1-C6烷基，以及可选择地取代的芳基，或者Rc和Rd一起形成可选择地取代的碳环或可选择地取代的杂环；R1为OH、OR、NR'R'、NHC(=O)R、NHSO2R；R2为H、F、C1、可选择地取代的C1-C20烷基，最好是可选择地取代的C1-C6烷基，可选择地取代的芳基或=O基团（与=O连接的碳形成羰基基团）；R3为H、OH、F、C1、Br、I、Cl、可选择地取代的C1-C20烷基、烯基或炔基（'烃基'），最好是可选择地取代的C1-C6烷基，或可选择地取代的芳基，使得R3连接的碳具有R或S构型；R为H、可选择地取代的C1-C20烷基，最好是可选择地取代的C1-C6烷基，或可选择地取代的芳基，R'和R'各自独立地为H、可选择地取代的C1-C20烷基，最好是可选择地取代的C1-C6烷基，或可选择地取代的芳基；或者R'和R'一起形成可选择地取代的杂环，最好是4到7成员的可选择地取代的杂环基团或与R'和R'连接的氮原子形成可选择地取代的杂芳基环；其中所述化合物不含金属催化剂。

  公开号：

  WO2006007586A1

文献信息

• Enantioselective Mannich Reactions with the Practical Proline Mimetic <i>N</i>-(<i>p</i>-Dodecylphenyl-sulfonyl)-2-pyrrolidinecarboxamide
  作者：Hua Yang、Rich G. Carter

  DOI：10.1021/jo8027938

  日期：2009.3.6

  highly enantioselective and diastereoselective protocol for performing Mannich reactions has been developed by using a p-dodecylphenylsulfonamide-based proline catalyst. This catalyst facilitates the use of common, nonpolar solvents and increased concentrations as compared to alternative methods. A series of syn-selective Mannich reactions is reported, including the rapid access of α- and β-amino acids surrogates

  通过使用基于对十二烷基苯基磺酰胺的脯氨酸催化剂，已经开发出用于进行曼尼希反应的高度对映选择性和非对映选择性的方案。与替代方法相比，该催化剂促进了普通非极性溶剂的使用并提高了浓度。一系列的顺式-选择性曼尼希反应报道，包括α-和β氨基酸替代物的快速存取。还证明了使用工业上有吸引力的非极性溶剂，例如2-甲基-四氢呋喃。
• 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
• Catalysis of highly stereoselective Mannich-type reactions of ketones with α-imino esters by a pyrrolidine-sulfonamide. Synthesis of unnatural α-amino acids
  作者：Wei Wang、Jian Wang、Hao Li

  DOI：10.1016/j.tetlet.2004.08.032

  日期：2004.9

  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.
• 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).
• [EN] ORGANOCATALYSTS AND METHODS OF USE IN CHEMICAL SYNTHESIS<br/>[FR] ORGANOCATALYSEURS ET PROCEDES D'UTILISATION DE CES DERNIERS DANS LA SYNTHESE CHIMIQUE
  申请人：STC UNM

  公开号：WO2006007586A1

  公开（公告）日：2006-01-19

  The present invention pertains generally to compositions comprising organocatalysts that facilitate stereo-selective reactions and the method of their synthesis and use. Particularly, the invention relates to metal-free organocatalysts for facilitation of stereo-­selective reactions, and the method of their synthesis and use. These compounds have the structure of the Formulas (I) and (II). Where X is independently selected from CH2, N-Ra, O, S or C=O; Y is CH2, N-Ra, O, S or C=O, with the proviso that at least one of X or Y is CH2, and preferably both of X and Y are CH2; Ra is H, an optionally substituted C1-C12 alkyl, preferably an optionally substituted C1-C6 alkyl including a C3-C6 cyclic alkyl group, or an optionally substituted aryl group, preferably an optionally substituted phenyl group; Rb is H, an optionally substituted C1-C12 alkyl, preferably an optionally substituted C1-C6 acyclic or a a C3-C6 cyclic alkyl group, CHO, N(Me)O, CO(S)Ra or the group of Formula (III). Where Rc and Rd are each independently H, F, C1, an optionally substituted C1-C20 alkyl, preferably an optionally substituted C1-C12 alkyl, more preferably a C1-C6 alkyl, and an optionally substituted aryl group, or together Rc and Rd form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; R1 is OH, OR, NR'R', NHC(=O)R, NHSO2R; R2 is H, F, C1, an optionally substituted C1-C20 alkyl, preferably an optionally substituted C1­C6 alkyl, an optionally substituted aryl group or a =O group (which establishes a carbonyl group with the carbon to which =O is attached; R3 is H, OH, F, C1, Br, I, Cl, an optionally substituted C1-C20 alkyl, alkenyl or alkynyl ('hydrocarbyl') group, preferably an optionally substituted C1-C6 alkyl, or an optionally substituted aryl, such that the carbon to which R3 is attached has an R or S configuration; R is H, an optionally substituted C1-C20 alkyl, preferably an optionally substituted C1-C6 alkyl, or an optionally substituted aryl group, R' and R' are each independently H, an optionally substituted C1-C20 alkyl group, preferably an optionally substituted C1-C6 alkyl, or an optionally substituted aryl group; or together R' and R' form an optionally substituted heterocyclic, preferably a 4 to 7 membered optionally substituted heterocyclic group or an optionally substituted heteroaryl ring with the nitrogen to which R' and R' are attached; and wherein said compound is free from a metal catalyst.

  本发明涉及一般包括有机催化剂的组合物，该催化剂促进立体选择性反应以及其合成和使用方法。特别地，本发明涉及无金属有机催化剂以促进立体选择性反应，以及其合成和使用方法。这些化合物具有以下结构的式（I）和（II）。其中X独立地选择自CH2、N-Ra、O、S或C=O；Y为CH2、N-Ra、O、S或C=O，但至少X或Y中的一个为CH2，最好是X和Y都为CH2；Ra为H、可选择地取代的C1-C12烷基，最好是可选择地取代的C1-C6烷基，包括C3-C6环烷基，或可选择地取代的芳基，最好是可选择地取代的苯基；Rb为H、可选择地取代的C1-C12烷基，最好是可选择地取代的C1-C6无环或C3-C6环烷基，CHO、N(Me)O、CO(S)Ra或式（III）的基团。其中Rc和Rd各自独立地为H、F、C1、可选择地取代的C1-C20烷基，最好是可选择地取代的C1-C12烷基，更好地是C1-C6烷基，以及可选择地取代的芳基，或者Rc和Rd一起形成可选择地取代的碳环或可选择地取代的杂环；R1为OH、OR、NR'R'、NHC(=O)R、NHSO2R；R2为H、F、C1、可选择地取代的C1-C20烷基，最好是可选择地取代的C1-C6烷基，可选择地取代的芳基或=O基团（与=O连接的碳形成羰基基团）；R3为H、OH、F、C1、Br、I、Cl、可选择地取代的C1-C20烷基、烯基或炔基（'烃基'），最好是可选择地取代的C1-C6烷基，或可选择地取代的芳基，使得R3连接的碳具有R或S构型；R为H、可选择地取代的C1-C20烷基，最好是可选择地取代的C1-C6烷基，或可选择地取代的芳基，R'和R'各自独立地为H、可选择地取代的C1-C20烷基，最好是可选择地取代的C1-C6烷基，或可选择地取代的芳基；或者R'和R'一起形成可选择地取代的杂环，最好是4到7成员的可选择地取代的杂环基团或与R'和R'连接的氮原子形成可选择地取代的杂芳基环；其中所述化合物不含金属催化剂。