(+/-)-ethyl (2R*,3R*)-4,4,4-trifluoro-3-(4-methoxyanilino)-2-methyl-butanoate

• 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*,3R*)-4,4,4-trifluoro-3-(4-methoxyanilino)-2-methyl-butanoate
• 英文别名: ethyl (2RS,3RS)-4,4,4-trifluoro-3-(4-methoxyanilino)-2-methylbutanoate；ethyl 4,4,4-trifluoro-3-((4-methoxyphenyl)amino)-2-methylbutanoate；ethyl (2R,3R)-4,4,4-trifluoro-3-(4-methoxyanilino)-2-methylbutanoate
• 化学式: C₁₄H₁₈F₃NO₃
• 分子量: 305.297
• InChiKey: ZKLLBCUNTTXXBD-BXKDBHETSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (+/-)-ethyl (2R*,3R*)-4,4,4-trifluoro-3-(4-methoxyanilino)-2-methyl-butanoate 在 ammonium cerium(IV) nitrate 作用下， 以 水 、 乙腈 为溶剂， 生成 ethyl (2RS,3RS)-3-amino-4,4,4-trifluoro-2-methylbutanoate
  参考文献：
  名称：

  New Strategy for the Stereoselective Synthesis of Fluorinated β-Amino Acids

  摘要：

  Racemic and chiral nonracemic alpha-substituted and alpha-unsubstituted beta-fluoroalkyl beta-amino acid derivatives 6 and 9 have been synthesized in two steps starting from fluorinated imidoyl chlorides 1 and ester enolates. This approach is based on the chemical reduction of previously obtained gamma-fluorinated beta-enamino esters 4 by using ZnI2/NaBH4 in a nonchelated aprotic medium (dry CH2Cl2) as the reducing agent. A metal-chelated six-membered model has been suggested to explain the stereochemical outcome of the reduction reaction. The process takes place with high yields and with moderate to good diastereoselectivity. The best results related to diastereoselective reduction of chiral beta-enamino esters 4 were provided by the use of (-)-8-phenylmenthol as a chiral auxiliary.

  DOI：

  10.1021/jo025621k
• 作为产物：
  描述：

  丙酸乙酯 在 sodium tetrahydroborate 、 zinc(II) iodide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 49.5h， 生成 (+/-)-ethyl (2R*,3R*)-4,4,4-trifluoro-3-(4-methoxyanilino)-2-methyl-butanoate
  参考文献：
  名称：

  New Strategy for the Stereoselective Synthesis of Fluorinated β-Amino Acids

  摘要：

  Racemic and chiral nonracemic alpha-substituted and alpha-unsubstituted beta-fluoroalkyl beta-amino acid derivatives 6 and 9 have been synthesized in two steps starting from fluorinated imidoyl chlorides 1 and ester enolates. This approach is based on the chemical reduction of previously obtained gamma-fluorinated beta-enamino esters 4 by using ZnI2/NaBH4 in a nonchelated aprotic medium (dry CH2Cl2) as the reducing agent. A metal-chelated six-membered model has been suggested to explain the stereochemical outcome of the reduction reaction. The process takes place with high yields and with moderate to good diastereoselectivity. The best results related to diastereoselective reduction of chiral beta-enamino esters 4 were provided by the use of (-)-8-phenylmenthol as a chiral auxiliary.

  DOI：

  10.1021/jo025621k

文献信息

• Synthesis of Chiral β-Fluoroalkyl β-Amino Acid Derivatives via Palladium-Catalyzed Hydrogenation
  作者：Mu-Wang Chen、Qin Yang、Zhihong Deng、Qiuping Ding、Yiyuan Peng

  DOI：10.1021/acs.joc.9b01523

  日期：2019.8.16

  An enantioselective palladium-catalyzed hydrogenation of β-fluoroalkyl β-amino acrylic acid derivatives has been successfully developed, providing the corresponding chiral β-fluoroalkyl β-amino acid derivatives in good yields with excellent enantioselectivities. In addition, chiral γ-fluoroalkyl γ-amino alcohol could be synthesized by a simple reduction of the corresponding hydrogenated product. The

  已经成功开发了对映选择性钯催化的β-氟烷基β-氨基丙烯酸衍生物的氢化反应，以良好的收率和优异的对映选择性提供了相应的手性β-氟烷基β-氨基酸衍生物。另外，可以通过简单还原相应的氢化产物来合成手性γ-氟烷基γ-氨基醇。通过氘标记实验探索了反应的机理。
• 一种钯催化不对称氢化合成手性含氟β-氨基酸衍生物的方法
  申请人：中国科学院大连化学物理研究所

  公开号：CN112209843B

  公开（公告）日：2023-03-03

  一种钯催化不对称氢化合成手性含氟β‑氨基酸衍生物的方法，其用到的催化体系是钯的手性双磷配合物。反应能在下列条件内进行，温度：0‑80℃；溶剂：2,2,2‑三氟乙醇或六氟异丙醇；压力：100‑1000psi；底物和催化剂的比例是25/l；用到的金属前体：三氟醋酸钯；用到的手性配体：手性双磷配体；催化剂的制备方法为：将钯的金属前体和手性双磷配体在丙酮中室温搅拌一小时，然后真空浓缩得到催化剂。对含氟烯胺的氢化能得到相应的手性含氟β‑氨基酸衍生物，其对映体过量可达到96％。本发明操作简便实用，对映选择性高，产率好，且反应具有绿色原子经济性，对环境友好。
• First Highly Diastereoselective Synthesis of <i>s</i><i>yn</i> α-Methyl β-Fluoroalkyl β-Amino Esters
  作者：Santos Fustero、Belén Pina、Marta García de la Torre、Antonio Navarro、Carmen Ramírez de Arellano、Antonio Simón

  DOI：10.1021/ol990774o

  日期：1999.10.1

  [GRAPHICS]A new two-step approach for the diastereoselective synthesis of the syn alpha-methyl beta-fluoroalkyl beta-amino esters 4 has been developed. This approach is based on the chemical reduction of the fluorinated beta-enamino esters 3, which have been previously obtained from imidoyl chlorides 1 and lithium ester enolates, with Znl(2)/NaBH4 as the reducing agent. The process takes place with high syn diastereoselectivity and good to excellent yields. A metal-chelated six-membered model has been suggested to explain the stereochemical outcome of the reduction reaction.
• New Strategy for the Stereoselective Synthesis of Fluorinated β-Amino Acids
  作者：Santos Fustero、Belén Pina、Esther Salavert、Antonio Navarro、M. Carmen Ramírez de Arellano、Antonio Simón Fuentes

  DOI：10.1021/jo025621k

  日期：2002.7.1

  Racemic and chiral nonracemic alpha-substituted and alpha-unsubstituted beta-fluoroalkyl beta-amino acid derivatives 6 and 9 have been synthesized in two steps starting from fluorinated imidoyl chlorides 1 and ester enolates. This approach is based on the chemical reduction of previously obtained gamma-fluorinated beta-enamino esters 4 by using ZnI2/NaBH4 in a nonchelated aprotic medium (dry CH2Cl2) as the reducing agent. A metal-chelated six-membered model has been suggested to explain the stereochemical outcome of the reduction reaction. The process takes place with high yields and with moderate to good diastereoselectivity. The best results related to diastereoselective reduction of chiral beta-enamino esters 4 were provided by the use of (-)-8-phenylmenthol as a chiral auxiliary.