ethyl (2S,3'R)-2-(p-methoxyphenylamino)-2-(4'-oxotetrahydrothiopyran-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 (2S,3'R)-2-(p-methoxyphenylamino)-2-(4'-oxotetrahydrothiopyran-3'-yl)acetate
• 英文别名: ethyl 2-((4-methoxyphenyl)amino)-2-(4-oxotetrahydro-2H-thiopyran-3-yl)acetate；ethyl (2S,3R)-2-(4-methoxyphenylamino)-2-(4'-oxotetrahydrothiopyran-3'-yl)acetate；ethyl (2S)-2-(4-methoxyanilino)-2-[(3R)-4-oxothian-3-yl]acetate
• 化学式: C₁₆H₂₁NO₄S
• 分子量: 323.413
• InChiKey: JZESJGYRPMTONK-ZFWWWQNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 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：
  89.9
• 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 (2S,3'R)-2-(p-methoxyphenylamino)-2-(4'-oxotetrahydrothiopyran-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

• 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。
• Enantioselective aerobic oxidative cross-dehydrogenative coupling of glycine derivatives with ketones and aldehydes <i>via</i> cooperative photoredox catalysis and organocatalysis
  作者：Xiaorong Yang、Zhixiang Xie、Ying Li、Yuan Zhang

  DOI：10.1039/d0sc00683a

  日期：——

  glycine derivatives and simple ketones or aldehydes, which provides an efficient approach for the rapid synthesis of enantiopure unnatural α-alkyl α-amino acid derivatives in good yield with excellent diastereo- (up to >99 : 1) and enantioselectivities (up to 97% ee). This process includes the direct photoinduced oxidation of glycine derivatives to an imine intermediate, followed by the asymmetric Mannich-type

  光氧化还原催化和烯胺催化的结合使甘氨酸衍生物与简单的酮或醛之间的对映选择性好氧氧化交叉脱氢偶联成为可能，这为快速合成对映纯的非天然α-烷基α-氨基酸衍生物提供了一种有效的方法。高收率，非对映异构体（高达> 99：1）和对映选择性（高达97％ee）。此过程包括将甘氨酸衍生物直接光诱导氧化为亚胺中间体，然后与原位生成的烯胺中间体进行不对称曼尼希型反应由酮或醛和手性仲胺有机催化剂制得。这种温和的方法可以直接形成C–C键，同时安装两个新的立体中心，而不会浪费掉官能团。
• A Designer Axially Chiral Amino Sulfonamide as an Efficient Organocatalyst for Direct Asymmetric<i>anti</i>-Selective Mannich Reactions and<i>syn</i>-Selective Cross-Aldol Reactions
  作者：Taichi Kano、Yukako Yamaguchi、Keiji Maruoka

  DOI：10.1002/chem.200900267

  日期：2009.7.6

  Amino sulfonamide catalyst: A distal proton of the axially chiral amino sulfonamide (S)‐1 realized the opposite diastereoselectivity in Mannich and cross‐aldol reactions compared with that observed in proline‐catalyzed reactions. The reactions catalyzed by (S)‐1 proceeded smoothly to give the anti‐Mannich and syn‐aldol adducts in excellent enantioselectivity (see scheme).

  氨基磺酰胺催化剂：与脯氨酸催化反应相比，轴向手性氨基磺酰胺（S）-1的远端质子在曼尼希和交叉羟醛反应中实现了相反的非对映选择性。由（S）-1催化的反应进行得很顺利，从而得到了具有出色对映选择性的抗曼尼希和顺式醇醛加合物（参见方案）。
• 4-Aminothiourea Prolinol<i>tert</i>-Butyldiphenylsilyl Ether: A Chiral Secondary Amine-Thiourea as Organocatalyst for Enantioselective<i>anti</i>-Mannich Reactions
  作者：Hui Zhang、Yongming Chuan、Zhengyu Li、Yungui Peng

  DOI：10.1002/adsc.200900399

  日期：2009.10

  anti-Selective Mannich reactions of N-p-methoxyphenyl (PMP)-protected α-iminoglyoxylate with unmodified aldehydes or ketones were effectively catalyzed by 4-aminothiourea prolinol tert-butyldiphenylsilyl ether. The reactions led to chiral β-amino carbonyl compounds in high yields (up to 94%), excellent diastereo- and enantioselectivities (up to 98% de and >99% ee). The study demonstrated for the first

  抗的-选择性曼尼希反应ñ - p -甲氧基苯基（PMP）与未改性的醛或酮-保护的α-iminoglyoxylate得到有效利用4-氨基硫脲脯氨醇催化叔-butyldiphenylsilyl醚。反应导致高收率（高达94％），出色的非对映异构和对映选择性（高达98％de和> 99％ee）的手性β-氨基羰基化合物。该研究首次证明，仲胺-硫脲手性有机催化剂可促进未修饰醛或酮与α-亚氨基乙醛酸酯的直接曼尼希型反应。
• TEMPO-Enabled Electrochemical Enantioselective Oxidative Coupling of Secondary Acyclic Amines with Ketones
  作者：Zhen-Hua Wang、Pei-Sen Gao、Xiu Wang、Jun-Qing Gao、Xue-Tao Xu、Zeng He、Cong Ma、Tian-Sheng Mei

  DOI：10.1021/jacs.1c08671

  日期：2021.9.29

  asymmetric coupling of secondary acyclic amines with ketones via a Shono-type oxidation has been described, affording the corresponding amino acid derivatives with good to excellent diastereoselectivity and enantioselectivity. The addition of an N-oxyl radical as a redox mediator could selectively oxidize the substrate rather than the product, although their oxidation potential difference is subtle (about

  已经描述了仲无环胺与酮通过 Shono 型氧化的电化学不对称偶联，提供了具有良好至优异的非对映选择性和对映选择性的相应氨基酸衍生物。添加N-氧基自由基作为氧化还原介质可以选择性氧化底物而不是产物，尽管它们的氧化电位差异很小（约 13 mV）。这种电化学转化在没有化学计量添加剂（包括金属、氧化剂和电解质）的情况下进行，这使其具有良好的官能团兼容性。机理研究表明，质子介导的产物外消旋化可通过阴极处质子的还原来防止。