ethyl (2R,3'R)-2-(p-methoxyphenylamino)-2-(4'-oxotetrahydropyran-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: ethyl (2R,3'R)-2-(p-methoxyphenylamino)-2-(4'-oxotetrahydropyran-3'-yl)acetate
• 英文别名: ethyl 2-(p-methoxyphenylamino)-2-(4’-oxotetrahydropyran-3’-yl)acetate；ethyl 2-[(4-methoxyphenyl)amino]-2-[4-oxotetrahydro-2H-pyran-3-yl]acetate；ethyl (2R,3S)-2-(4-methoxyphenylamino)-2-(4'-oxotetrahydropyran-3'-yl)acetate；ethyl (2R)-2-(4-methoxyanilino)-2-[(3R)-4-oxooxan-3-yl]acetate
• 化学式: C₁₆H₂₁NO₅
• 分子量: 307.346
• InChiKey: VDHDJWMNQOFGMW-UKRRQHHQSA-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 在 (R)-吡咯烷-3-羧酸 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 6.0h， 生成 ethyl (2R,3'R)-2-(p-methoxyphenylamino)-2-(4'-oxotetrahydropyran-3'-yl)acetate
  参考文献：
  名称：

  3-Pyrrolidinecarboxylic Acid for Direct Catalytic Asymmetric anti-Mannich-Type Reactions of Unmodified Ketones

  摘要：

  We report the development of direct catalytic, enantioselective, anti-selective Mannich-type reactions between unmodified ketones and alpha-imino esters under mild conditions. The reactions were performed using 5-10 mol % of (R)-3-pyrrolidinecarboxylic or (R)-beta-proline as catalyst in an environmentally benign solvent, 2-PrOH, at room temperature. The anti-Mannich products were obtained in good yields with high diastereo- and enantioselectivities (up to anti/syn >99:1, 99% ee). While (3R,5R)-5-methyl-3-pyrrolidinecarboxylic acid is an excellent catalyst for the anti-Mannich-type reactions of aldehydes, it did not efficiently catalyze the corresponding Mannich-type reactions of ketones; (R)-3-pyrrolidinecarboxylic acid did efficiently catalyze the Mannich-type reactions of ketones. (S)-Proline or (S)-2-pyrrolidinecarboxylic acid has been reported to catalyze the Mannich-type reactions of ketones to afford the syn-products. Thus, the position of the carboxylic acid group on the pyrrolidine ring directs the stereoselection of the catalyzed reaction, providing either syn- or anti-Mannich products.

  DOI：

  10.1021/ja062950b

文献信息

• Highly Active Organocatalysts for Asymmetric anti-Mannich Reactions
  作者：Rafael Martín-Rapún、Xinyuan Fan、Sonia Sayalero、Mahboubeh Bahramnejad、Félix Cuevas、Miquel A. Pericàs

  DOI：10.1002/chem.201101513

  日期：2011.8.1

  of enantiopure 4‐oxy‐substituted 3‐aminopyrrolidines arising from the enantioselective ring‐opening of meso‐3‐pyrroline oxide have been developed as catalysts for the asymmetric, anti‐selective Mannich reaction (see scheme; PMP=p‐methoxyphenyl; PG=protecting group). Very high catalytic activity (down to 0.01 mol % loading) and stereoselectivity have been recorded.

  减轻负担！已经开发了由内消旋3-吡咯啉氧化物的对映选择性开环产生的对映纯4-氧取代的3-氨基吡咯烷类，作为不对称，反选择性曼尼希反应的催化剂（见方案； PMP =对甲氧基苯基； PG ＝保护基）。记录到非常高的催化活性（低至0.01 mol％的负载量）和立体选择性。
• Asymmetric Synthesis and Catalytic Activity of 3-Methyl-β-proline in Enantioselective <i>anti</i>-Mannich-type Reactions
  作者：Kazuhiro Nagata、Yasushi Kuga、Akinori Higashi、Atsushi Kinoshita、Takuya Kanemitsu、Michiko Miyazaki、Takashi Itoh

  DOI：10.1021/jo4010316

  日期：2013.7.19

  Enantiomerically pure 3-methyl-β-proline was synthesized using an asymmetric phase-transfer-catalyzed alkylation of a cyanopropanoate to establish the all-carbon stereogenic center. The catalytic activity of 3-methyl-β-proline in the Mannich-type reaction between a glyoxylate imine and ketones/aldehydes was subsequently investigated. The catalyst was designed and found to be more soluble in nonpolar

  使用氰基丙酸酯的不对称相转移催化烷基化合成对映体纯的3-甲基-β-脯氨酸，以建立全碳立体异构中心。随后研究了3-甲基-β-脯氨酸在乙醛酸亚胺与酮/醛之间的曼尼希型反应中的催化活性。设计该催化剂，发现该催化剂相对于未取代的β-脯氨酸催化剂更溶于非极性有机溶剂，因此可以在优化过程中增加灵活性。这项工作在一个高度发展高潮抗采用低催化剂装载-diastereo-和对映选择性方法。
• Enantioselective anti-Mannich reaction catalyzed by modularly designed organocatalysts
  作者：Swapna Konda、John C.-G. Zhao

  DOI：10.1016/j.tet.2018.09.006

  日期：2018.10

  te was realized using the modularly designed organocatalysts (MDOs) self-assembled from cinchona alkaloid derivatives and (R)-pyrrolidien-3-carboxylic acid in the reaction media. The desired anti-Mannich products were obtained in good to excellent yields (up to 93%), excellent diastereoselectivities (up to 99:1 dr), and good to high enantioselectivities (up to 99% ee).

  利用金鸡纳生物碱衍生物和( R )-吡咯烷-3-羧基自组装的模块化设计的有机催化剂(MDO)，实现了醛和酮与(4-甲氧基苯基亚氨基)乙酸乙酯的反曼尼希反应的高度立体选择性方法反应介质中的酸。所需的抗曼尼希产物以良好到优异的产率（高达 93%）、优异的非对映选择性（高达 99:1 dr）和良好到高的对映选择性（高达 99% ee）获得。
• 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。
• 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.