ethyl (2R,3S)-2-(p-methoxyphenylamino)-3-methyl-4-oxohexanoate

• 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,3S)-2-(p-methoxyphenylamino)-3-methyl-4-oxohexanoate
• 英文别名: ethyl 2-(p-methoxyphenylamino)-3-methyl-4-oxohexanoate；ethyl (2S,3S)-2-(p-methoxyphenylamino)-3-methyl-4-oxohexanoate；ethyl (2R,3S)-2-(4-methoxyanilino)-3-methyl-4-oxohexanoate
• 化学式: C₁₆H₂₃NO₄
• 分子量: 293.363
• InChiKey: AGVCIAKDKNOFTN-IAQYHMDHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  甲氧苯胺 在 (S)-trifluoro-N-(pyrrolidin-3-ylmethyl)methanesulfonamide 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 78.0h， 生成 ethyl (2R,3S)-2-(p-methoxyphenylamino)-3-methyl-4-oxohexanoate
  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

• 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CH2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。
• Design of a C2-symmetric chiral pyrrolidine-based amino sulfonamide: application to anti-selective direct asymmetric Mannich reactions
  作者：Taichi Kano、Yoshio Hato、Keiji Maruoka

  DOI：10.1016/j.tetlet.2006.09.147

  日期：2006.11

  The anti-selective direct asymmetric Mannich reaction was found to be efficiently catalyzed by the novel pyrrolidine-based amino sulfonamide (R,R)-2 prepared from l-tartaric acid.

  所述抗-选择性直接不对称曼尼希反应被发现通过新的吡咯烷基氨基磺酰胺（被有效地催化- [R ，- [R ）- 2从1-酒石酸制备。
• Asymmetric anti-Mannich reactions in continuous flow
  作者：Rafael Martín-Rapún、Sonia Sayalero、Miquel A. Pericàs

  DOI：10.1039/c3gc41444b

  日期：——

  A polystyrene-supported, pyrrolidine-based catalyst depicting very high activity and excellent stereoselectivity in the anti-Mannich reaction of aldehydes and ketones has been developed. The very robust, immobilized catalyst has been successfully used in the implementation of a continuous flow process with short residence times (down to 6 min) for the production of highly enantioenriched anti-type Mannich adducts at the preparative scale.

  开发了一种在醛和酮的反曼尼希反应中表现出极高活性和优异立体选择性的聚苯乙烯负载吡咯烷基催化剂。这种非常坚固的固定化催化剂已成功应用于连续流动工艺的实施，该工艺具有短停留时间（低至6分钟），用于制备规模上生产高度对映体富集的反式曼尼希加合物。
• 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。
• 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.