ethyl 2-((4-fluorophenyl)amino)-2-(1H-indol-3-yl)acetate

• 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 2-((4-fluorophenyl)amino)-2-(1H-indol-3-yl)acetate
• 英文别名: ethyl 2-(4-fluoroanilino)-2-(1H-indol-3-yl)acetate
• 化学式: C₁₈H₁₇FN₂O₂
• 分子量: 312.344
• InChiKey: HFFSQMHVYXAFTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  苯甲基苯胺 、 ethyl 2-((4-fluorophenyl)amino)-2-(1H-indol-3-yl)acetate 在 scandium tris(trifluoromethanesulfonate) 作用下， 以 1,2-二氯乙烷 为溶剂， 以86%的产率得到ethyl 2-(4-(benzylamino)phenyl)-2-(1H-indol-3-yl)acetate
  参考文献：
  名称：

  Synthesis of Unsymmetrical α,α-Diarylacetates

  摘要：

  Ethyl bromofluoroacetate has been developed as a precursor for the convenient synthesis of unsymmetrical alpha,alpha-diarylacetates featuring indoles, anilines, and other electron-rich aromatics. In conjunction with a mild Lewis acid catalyzed C-N -> C-C exchange, intermediate arylglycines can be synthesized and transformed into alpha,alpha a-diarylacetates in a one-pot protocol, resulting in a net diarylation reaction exhibiting a wide scope. In the context of diarylacetates, the synthetic equivalence of the fluorinated reagent with a-nitro-a-diazo carbonyls was established.

  DOI：

  10.1021/acs.joc.5b02383
• 作为产物：
  描述：

  吲哚 、 2-[(4-氟苯基)氨基]乙酸乙酯 在 叔丁基过氧化氢 、 cobalt(II) acetylacetonate hydrate 作用下， 以 水 、 乙腈 为溶剂， 反应 24.0h， 以52%的产率得到ethyl 2-((4-fluorophenyl)amino)-2-(1H-indol-3-yl)acetate
  参考文献：
  名称：

  甘氨酸和肽衍生物的共催化C（sp 3）–H氧化偶联

  摘要：

  描述了钴催化的α-氨基酯和肽衍生物的选择性α-烷基化和α-杂芳基化过程。这些交叉脱氢反应在温和的条件下发生，并允许结构多样的α-氨基羰基化合物的快速组装。与烯醇式化学不同，这些方法的特征在于其位点特异性，在不消旋现有手性中心的情况下发生，并且相对于其他氨基酸单元表现出对芳基甘氨酸基序的总选择性，因此为肽修饰提供了充足的机会。

  DOI：

  10.1021/acs.orglett.7b02567

文献信息

• Arylation of Diazoesters by a Transient NH Insertion Organocascade
  作者：Tyler J. Auvil、Sonia S. So、Anita E. Mattson

  DOI：10.1002/anie.201304921

  日期：2013.10.18

  two: A unique organocatalyzed cascade for the unsymmetric double arylation of α‐nitrodiazoesters is described. This organocascade features the strategic use of carbene‐activating anilines in conjunction with a urea catalyst, thus allowing for the synthesis of pharmaceutically attractive α‐diarylesters through a transient NH insertion process.

  它需要两个步骤：描述了一个独特的有机催化级联，用于α-硝基重氮酯的不对称双芳基化。此organocascade设有与尿素催化剂一起战略性使用卡宾活化苯胺的，从而允许用于药学吸引力α-diarylesters通过瞬时合成N  ħ插入过程。
• Brønsted acid promoted C–C bond formation between indolylmethyl electrophiles and ketene dithioacetals: Diastereoselective synthesis of highly functionalized cyclopenta[b]indoles
  作者：Santosh D. Jadhav、Tavinder Singh、Anand Singh

  DOI：10.1016/j.tetlet.2020.152349

  日期：2020.9

  method for the construction of carbon–carbon bonds between α-substituted indolylmethyl electrophiles and ketene dithioacetals is described. This strategy was utilized to access 2,3-disubstituted cyclopenta[b]indoles via formal [3+2] cycloadditions. Readily available indolyl methanols and α-indolyl-α-amino carbonyl compounds serve as electrophiles upon activation by p-toluenesulfonic acid (PTSA) and react

  描述了一种布朗斯台德酸促进的方法，用于在α取代的吲哚基甲基亲电子试剂和乙烯酮二硫缩醛之间建立碳-碳键。利用该策略通过正式的[3 + 2]环加成反应获得2,3-二取代的环戊[ b ]吲哚。现成的吲哚基甲醇和α-吲哚基-α-氨基羰基化合物经p活化后可作为亲电子试剂-甲苯磺酸（PTSA）与乙烯酮二硫缩醛反应，形成两个碳-碳键和一个具有出色的非对映选择性的五元环。采用结构相关的吲哚基前体以实现分子多样性的优势被关键的替代作用所突显，这些作用突出了机理上的差异并指导了反应的发展。
• Urea-Catalyzed N–H Insertion–Arylation Reactions of Nitrodiazoesters
  作者：Sonia S. So、Shameema Oottikkal、Jovica D. Badjić、Christopher M. Hadad、Anita E. Mattson

  DOI：10.1021/jo500698q

  日期：2014.6.6

  The power of hydrogen-bond donor catalysis has been harnessed to elicit and control carbene-like reactivity from nitrodiazoesters. Specifically, select ureas have been identified as effective catalysts for N-H insertion and multicomponent coupling reactions of nitrodiazoesters, anilines, and aromatic nucleophiles, thereby preparing a variety of alpha-aryl glycines in high yield. Experimental and computational studies designed to probe the plausible reaction pathways suggest that difluoroboronate ureas are particularly well-suited to catalyze reactions of nitrodiazoesters with a range of anilines through a polar reaction pathway Urea-facilitated loss of nitrite followed by addition of a nucleophile conceivably generates the observed aryl glycine products.
• Synthesis of Unsymmetrical α,α-Diarylacetates
  作者：Santosh D. Jadhav、Anand Singh

  DOI：10.1021/acs.joc.5b02383

  日期：2016.1.15

  Ethyl bromofluoroacetate has been developed as a precursor for the convenient synthesis of unsymmetrical alpha,alpha-diarylacetates featuring indoles, anilines, and other electron-rich aromatics. In conjunction with a mild Lewis acid catalyzed C-N -> C-C exchange, intermediate arylglycines can be synthesized and transformed into alpha,alpha a-diarylacetates in a one-pot protocol, resulting in a net diarylation reaction exhibiting a wide scope. In the context of diarylacetates, the synthetic equivalence of the fluorinated reagent with a-nitro-a-diazo carbonyls was established.
• Co-Catalyzed C(sp³)–H Oxidative Coupling of Glycine and Peptide Derivatives
  作者：Marcos San Segundo、Itziar Guerrero、Arkaitz Correa

  DOI：10.1021/acs.orglett.7b02567

  日期：2017.10.6

  peptide derivatives are described. These cross-dehydrogenative reactions occur under mild conditions and allow for the rapid assembly of structurally diverse α-amino carbonyl compounds. Unlike enolate chemistry, these methods are distinguished by their site-specificity, occur without racemization of the existing chiral centers, and exhibit total selectivity for aryl glycine motifs over other amino acid

  描述了钴催化的α-氨基酯和肽衍生物的选择性α-烷基化和α-杂芳基化过程。这些交叉脱氢反应在温和的条件下发生，并允许结构多样的α-氨基羰基化合物的快速组装。与烯醇式化学不同，这些方法的特征在于其位点特异性，在不消旋现有手性中心的情况下发生，并且相对于其他氨基酸单元表现出对芳基甘氨酸基序的总选择性，因此为肽修饰提供了充足的机会。