ethyl (2S,3R)-3-acetyl-6-chloro-2-(p-methoxyphenylamino)hexanoate

• 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 (2S,3R)-3-acetyl-6-chloro-2-(p-methoxyphenylamino)hexanoate
• 英文别名: ethyl (2S,3R)-3-acetyl-6-chloro-2-(4-methoxyanilino)hexanoate
• 化学式: C₁₇H₂₄ClNO₄
• 分子量: 341.835
• InChiKey: NAKZUTZGXLTPQQ-HOTGVXAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 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 (R)-吡咯烷-3-羧酸 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 20.0h， 生成 ethyl (2S,3R)-3-acetyl-6-chloro-2-(p-methoxyphenylamino)hexanoate
  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。
• 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.
• [EN] TRANS-3,5-DISUBSTITUTEDPYRROLIDINE: ORGANOCATALYST FOR ANTI-MANNICH REACTIONS<br/>[FR] PYRROLIDINE TRANS-3,5-DISUBSTITUEE: ORGANOCATALYSEUR POUR REACTIONS ANTI-MANNICH
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2007062316A2

  公开（公告）日：2007-05-31

  [EN] 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 CH₂, 0, S or NR¹, wherein R^l is a hydrocarbyl group or an amino-protecting group having one to about 18 carbon atoms; R² is hydrido or a hydrocarbyl group containing one to about twelve carbon atoms,- and R³ is hydrido or methyl, but both R² and R³ are not hydrido when X is CH₂ (I) A molecule of Formula I and those in which R² and R³ can both be hydrido (Formula X) functions as a catalyst in a Mannich reaction to asymmetrically form ß- aminoaldehyde or ß- 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.
  [FR] L'invention concerne un composé représenté par la formule I, dans lequel R représente un substituant contenant un atome formant une liaison hydrogène dans un groupe de trois atomes provenant du noyau carbone auquel le substituant est lié; X représente CH₂, O, S ou NR¹, R¹ représentant un groupe hydrocarbyle ou un groupe amino protecteur comportant de un à environ 18 atomes de carbone; R² représente hydrido ou un groupe hydrocarbyle contenant de un à environ douze atomes de carbone; et R³ représente hydrido ou méthyle, mais R² et R³ ne représentent par hydrido lorsque X représente CH₂. (Formule I). L'invention concerne une molécule représentée par la formule I, dans laquelle R² et R³ peuvent représenter des fonctions hydrido (formule X), qui sert de catalyseur dans une réaction de Mannich permettant de former asymétriquement des produits diastéréomères de ß-aminoaldéhyde ou de ß-aminocétone comportant deux centres chiraux sur des atomes de carbone adjacents, et dans laquelle les anti-diastéréomères sont en excès par rapport aux diastéréomères syn-. Des procédés de mise en oeuvre de ces synthèses sont également décrits.
• 3-Pyrrolidinecarboxylic Acid for Direct Catalytic Asymmetric <i>a</i><i>nti</i>-Mannich-Type Reactions of Unmodified Ketones
  作者：Haile Zhang、Maria Mifsud、Fujie Tanaka、Carlos F. Barbas

  DOI：10.1021/ja062950b

  日期：2006.8.1

  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.