(Z)-2-Acetylamino-3-(3,5-difluoro-phenyl)-acrylic acid methyl ester

• 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: (Z)-2-Acetylamino-3-(3,5-difluoro-phenyl)-acrylic acid methyl ester
• 英文别名: (Z)-methyl 2-acetamido-3-(3,5-difluorophenyl)acrylate；methyl (Z)-2-acetamido-3-(3,5-difluorophenyl)prop-2-enoate
• 化学式: C₁₂H₁₁F₂NO₃
• 分子量: 255.221
• InChiKey: HEHBAQWTEUZOLP-WZUFQYTHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (Z)-2-Acetylamino-3-(3,5-difluoro-phenyl)-acrylic acid methyl ester 在 phosphino>-β-D-glucopyranoside>Rh(COD)>⁺SbF6^- 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 N-acetyl-3,5-difluorophenylalanine methyl ester
  参考文献：
  名称：

  Carbohydrate Phosphinites as Practical Ligands in Asymmetric Catalysis:  Electronic Effects and Dependence of Backbone Chirality in Rh-Catalyzed Asymmetric Hydrogenations. Synthesis of R- or S-Amino Acids Using Natural Sugars as Ligand Precursors

  摘要：

  Vicinal diarylphosphinites derived from carbohydrates are excellent ligands for the Rh(I)-catalyzed enantioselective asymmetric hydrogenation of dehydroamino acid derivatives, producing the highest enantioselectivity of any ligands directly prepared from natural products. The enantioselectivity can be enhanced by the appropriate choice of substituents on the aromatic rings of the phosphinites. For example, the use of phosphinites with electron-donating bis(3,5-dimethylphenyl) groups on phosphorus provides ee's up to 99% for a wide range of amino acids including some with easily removable N-protecting groups. Electron-withdrawing aryl substituents, on the other hand, decrease the enantioselectivity. Sense of chiral induction in the amino acid product depends on the relative juxtaposition of the vicinal diphosphinites on a given sugar backbone. When readily available D-glucopyranosides are used as the starting sugars, 2,3-phosphinites give the S-amino acids and 3,4-phosphinites give the R-amino acids. In the case of aromatic and heteroaromatic amino acids, enantioselectivities > 95% are consistently obtained. Practical considerations such as the ease of ligand synthesis, rates of reactions, catalyst turnover, and scope and limitations in terms of substrates are discussed. A possible explanation for the enhancement of enantioselectivity by electron-rich phosphinites is offered.

  DOI：

  10.1021/jo970884d

文献信息

• Electronic Amplification of Selectivity in Rh-Catalyzed Hydrogenations: D-Glucose-Derived Ligands for the Synthesis of D- or L-Amino Acids
  作者：T. V. RajanBabu、Timothy A. Ayers、Albert L. Casalnuovo

  DOI：10.1021/ja00088a065

  日期：1994.5

  elimination.5~6 Only a few examples have been documented where electronic tuning of a ligand system has resulted in an enhancement of enant iosele~t ivi ty .~-~~ Previously we demonstrated that the enantioselectivity of the Ni(0)-catalyzed asymmetric hydrocyanation of olefins was dramatically improved when phosphinites with electron-withdrawing substituents a t phosphorus were employed as ligandsS8 In

  过渡金属配合物的不对称催化在过去十年中取得了巨大进步，但即使在已被广泛研究的反应中，对于实现高对映选择性很重要的因素仍然是推测的主题。 2 大多数情况下，基于空间位阻的启发式模型论据被用于结果的合理化 3 和更具选择性的催化剂的设计^。^ 电子效应很少被用作对映选择性的控制元素，尽管这种效应长期以来被认为在初级有机金属过程中很重要，例如氧化加法和还原消除。5~6 只有少数几个例子被记录在案，其中配体系统的电子调谐导致对映选择性的增强。～～～～～～～～此前，我们证明了当在磷上具有吸电子取代基的亚膦酸盐用作配体时，Ni(0)催化的烯烃不对称氢氰化的对映选择性得到显着提高。 Rh(1) 催化的乙酰氨基丙烯酸酯 1 (eq l) 的不对称氢化。] 在这种情况下，富含电子的次膦酸盐提供了高度富电子次膦酸盐提供了一个高度富电子次膦酸盐提供了一个高度
• Carbohydrate Phosphinites as Practical Ligands in Asymmetric Catalysis:  Electronic Effects and Dependence of Backbone Chirality in Rh-Catalyzed Asymmetric Hydrogenations. Synthesis of <i>R</i>- or <i>S</i>-Amino Acids Using Natural Sugars as Ligand Precursors
  作者：T. V. RajanBabu、Timothy A. Ayers、Gary A. Halliday、Kimberly K. You、Joseph C. Calabrese

  DOI：10.1021/jo970884d

  日期：1997.8.1

  Vicinal diarylphosphinites derived from carbohydrates are excellent ligands for the Rh(I)-catalyzed enantioselective asymmetric hydrogenation of dehydroamino acid derivatives, producing the highest enantioselectivity of any ligands directly prepared from natural products. The enantioselectivity can be enhanced by the appropriate choice of substituents on the aromatic rings of the phosphinites. For example, the use of phosphinites with electron-donating bis(3,5-dimethylphenyl) groups on phosphorus provides ee's up to 99% for a wide range of amino acids including some with easily removable N-protecting groups. Electron-withdrawing aryl substituents, on the other hand, decrease the enantioselectivity. Sense of chiral induction in the amino acid product depends on the relative juxtaposition of the vicinal diphosphinites on a given sugar backbone. When readily available D-glucopyranosides are used as the starting sugars, 2,3-phosphinites give the S-amino acids and 3,4-phosphinites give the R-amino acids. In the case of aromatic and heteroaromatic amino acids, enantioselectivities > 95% are consistently obtained. Practical considerations such as the ease of ligand synthesis, rates of reactions, catalyst turnover, and scope and limitations in terms of substrates are discussed. A possible explanation for the enhancement of enantioselectivity by electron-rich phosphinites is offered.