ethyl 3,3,3-trifluoro-2-hydroxy-2-(2-methyl-1H-indol-3-yl)propanoate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl 3,3,3-trifluoro-2-hydroxy-2-(2-methyl-1H-indol-3-yl)propanoate
• 英文别名: (S)-ethyl 3,3,3-trifluoro-2-hydroxy-2-(2-methyl-1H-indol-3-yl)-propanoate；ethyl (2S)-3,3,3-trifluoro-2-hydroxy-2-(2-methyl-1H-indol-3-yl)propanoate
• 化学式: C₁₄H₁₄F₃NO₃
• 分子量: 301.265
• InChiKey: OKLMMCIKGHSFQE-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  62.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-甲基吲哚 、 三氟乙酸乙酯 在 CSCS 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以96%的产率得到ethyl 3,3,3-trifluoro-2-hydroxy-2-(2-methyl-1H-indol-3-yl)propanoate
  参考文献：
  名称：

  Enhanced efficiency of recyclable C3-symmetric cinchonine-squaramides in the asymmetric Friedel–Crafts reaction of indoles with alkyl trifluoropyruvate

  摘要：

  The highly enantioselective Friedel-Crafts reaction of indoles with trifluoropyruvate catalyzed by a C-3-symmetric cinchonine-squaramide is reported. A wide variety of trifluoromethylated indole derivatives were obtained in high yields and with excellent enantioselectivities (99% and up to > 99% ee). Moreover the C-3 catalyst can be easily recovered and was used five times. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2012.08.015

文献信息

• Novel Enantiocomplementary<i>C</i>₂‐Symmetric Chiral Bis(imidazoline) Ligands: Highly Enantioselective Friedel–Crafts Alkylation of Indoles with Ethyl 3,3,3‐Trifluoropyruvate
  作者：Shuichi Nakamura、Kengo Hyodo、Yuko Nakamura、Norio Shibata、Takeshi Toru

  DOI：10.1002/adsc.200800189

  日期：2008.7.7

  Enantioselective Friedel–Crafts alkylations of a variety of indoles with ethyl 3,3,3-trifluoropyruvate catalyzed by novel chiral m-phenylenebis(imidazoline)-copper(II) complexes or the bis(imidazoline)-achiral acid combination afforded products with high enantioselectivity. Both enantiomers of indole derivatives can be prepared with high enantioselectivities by tuning the N-substituents of the imidazoline

  的各种吲哚的对映选择性的Friedel-Crafts烷基化反应与由新型手性催化乙基3,3,3-三氟丙酮米-phenylenebis（咪唑啉） -铜（II）配合物或双（咪唑啉）-achiral酸组合得到的产品具有高对映选择性。吲哚衍生物的两种对映异构体可以通过调节咪唑啉的N-取代基而以高对映选择性制备。
• Asymmetric Friedel–Crafts Alkylation of Indoles with Trifluoromethyl Pyruvate Catalyzed by a Dinuclear Zinc Catalyst
  作者：Yuan-Zhao Hua、Jun-Wei Chen、Hua Yang、Min-Can Wang

  DOI：10.1021/acs.joc.7b02599

  日期：2018.2.2

  cooperative catalysis model has been reported for the asymmetric Friedel–Crafts (F–C) alkylation of indoles with trifluoromethyl pyruvates using Trost’s intramolecular dinuclear zinc complex as the catalyst. This dinuclear zinc catalyst was prepared in situ by reacting the chiral ligand (S,S)-L2b with 2 equiv of ZnEt2. A series of trifluoromethyl alcohol and indole-containing biological compounds were formed

  据报道，使用Trost分子内双核锌络合物作为催化剂，吲哚与三氟甲基丙酮酸酯的不对称Friedel-Crafts（FC）烷基化的双金属协同催化模型。这种双核锌催化剂通过手性配体（反应原位制备S，S - ）L2b的与2当量ZnEt的2。在温和的条件下，在10 mol％的催化剂存在下，以中等至良好的收率（高达95％）和良好的对映选择性（高达88％对映体过量（ee））形成一系列三氟甲醇和含吲哚的生物化合物。提出了一种协同过渡状态模型来解释不对称感应的起源。
• Enantioselective inhibition of reverse transcriptase (RT) of HIV-1 by non-racemic indole-based trifluoropropanoates developed by asymmetric catalysis using recyclable organocatalysts
  作者：Xin Han、Wenjie Ouyang、Bin Liu、Wei Wang、Po Tien、Shuwen Wu、Hai-Bing Zhou

  DOI：10.1039/c3ob41667d

  日期：——

  Herein, we report the development of efficient inhibitors of reverse transcriptase (RT) of HIV-1 based on indole-alkyl trifluoropyruvate derivatives by a TZM-bl cell assay. The inhibitory activities of the two enantiomers and the corresponding racemic mixture have been compared. TZM-bl cells exhibited strong enantioselective discrimination for the (R)-configuration, among these indole derivatives, the most active compound R-12, with a 5-NO2 substituent, gave the best result when tested in the TZM-bl cells on HIV virus type HIV-1IIIB, with an EC50 value of 0.019 μM, CC50 value of 210.697 μM and SI (selectivity index, CC50/EC50) value of 11 089, respectively. The cell test showed that, in most cases, the R-enantiomer was superior to the Rac-mixture, which was better than the corresponding S-enantiomer. The results indicated that the R-enantiomer is the most favorable configuration as an efficient HIV-1 inhibitor. Molecular modeling studies suggested a structural basis for the enantioselectivity of RT towards this class of molecules.

  在此，我们报道了基于吲哚-烷基三氟丙酮酸衍生物的高效HIV-1逆转录酶（RT）抑制剂的开发，通过TZM-bl细胞 assay进行。已经比较了两种对映体及其相应的消旋混合物的抑制活性。TZM-bl细胞对这些吲哚衍生物中的(R)-构型表现出强烈的立体选择性辨别。在这些吲哚衍生物中，活性最强的化合物R-12，带有一个5-NO2取代基，在TZM-bl细胞中对HIV病毒类型HIV-1IIIB进行测试时，得到了最好的结果，其EC50值为0.019 μM，CC50值为210.697 μM，SI（选择性指数，CC50/EC50）值为11089。细胞测试表明，在大多数情况下，R-对映体优于消旋混合物，后者又优于相应的S-对映体。结果表明，R-对映体是最有利于作为高效HIV-1抑制剂的构型。分子建模研究为RT对这类分子的立体选择性提供了结构基础。
• Enantioselective Friedel–Crafts alkylation of indole derivatives catalyzed by new Yb(OTf)₃-pyridylalkylamine complexes as chiral Lewis acids
  作者：Guillaume Grach、Aurelia Dinut、Sylvain Marque、Jérôme Marrot、Richard Gil、Damien Prim

  DOI：10.1039/c0ob00461h

  日期：——

  New Yb(OTf)3-pyridylalkylamine complexes have been employed as chiral Lewis acids in the enantioselective Friedel–Crafts alkylation of indole derivatives with trifluoropyruvates. The influence of the substituents as well as the configuration of the ligands have been studied and allowed us to reach enantiomeric excesses up to 83%.

  新型的Yb(OTf)3-吡啶基烷基胺配合物已被用作手性Lewis酸，在三氟丙酮酸存在下进行吲哚衍生物的非对映选择性Friedel-Crafts烷基化反应。我们研究了取代基及配体构型的影响，并实现了高达83%的对映体过量。
• On the molecular structure and geometry of pyridylalkylamine–H+ complexes: application to catalytic enantioselective hydroxyalkylation of indoles
  作者：Sylvain Marque、Vanessa Razafimahaléo、Aurelia Dinut、Guillaume Grach、Damien Prim、Xavier Moreau、Richard Gil

  DOI：10.1039/c3nj00310h

  日期：——

  The protonation of 2-pyridylalkylamines (PAA) was investigated through quantum chemical calculations at a DFT level of theory in dichloromethane solution. Two different PAA–H+ species and a dynamic equilibrium between protonated forms were evidenced. The overall geometry of the PAA–H+ promoters is strongly influenced by the nature of the moiety and the absolute configuration of the pseudobenzylic stereocenter. Thus, PAA–H+ complexes were used as organocatalysts in the enantioselective hydroxyalkylation of indole derivatives. The combination of PAA, a strong acid and a soft counter-ion was found to be a mandatory parameter to achieve high yields and selectivities allowing hydroxyalkylation of both N–H and N-protected indoles using a unique catalytic system.

  对2-吡啶基烷基胺（PAA）的质子化进行了通过量子化学计算的研究，采用DFT理论水平在二氯甲烷溶液中进行。实验表明存在两种不同的PAA-H+物种及其质子化形式之间的动态平衡。PAA-H+促进剂的整体几何构型受到取代基的性质和伪苄基立体中心的绝对构型的强烈影响。因此，PAA-H+复合物被用作吲哚衍生物的对映选择性羟基烷基化的有机催化剂。研究发现，PAA、强酸和软对离子相结合是实现高产率和选择性的必要参数，这使得使用独特的催化系统能够对N-H和N保护的吲哚进行羟基烷基化反应。