(R)-tert-butyl (1-benzyl-3-(nitromethyl)-2-oxoindolin-3-yl)carbamate | 1606996-82-0

• 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: (R)-tert-butyl (1-benzyl-3-(nitromethyl)-2-oxoindolin-3-yl)carbamate
• 英文别名: tert-butyl N-[(3R)-1-benzyl-3-(nitromethyl)-2-oxoindol-3-yl]carbamate
• CAS: 1606996-82-0
• 化学式: C₂₁H₂₃N₃O₅
• 分子量: 397.431
• InChiKey: JBTCPJYRFSCDFY-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl (1-benzyl-3-(nitromethyl)-2-oxoindolin-3-yl)carbamate 在 tin(II) chloride dihdyrate 、 苯硫酚 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 0.33h， 生成 C₂₁H₂₃N₃O₄
  参考文献：
  名称：

  手性双功能胍催化的伊斯兰衍生的Kettimines的对映选择性氮杂-亨利反应。

  摘要：

  通过使用手性胍-酰胺有机催化剂，可以实现有效的不对称的伊斯汀衍生酮亚胺氮杂亨利反应。获得了一系列3-取代的3-氨基-2-氧吲哚，具有优异的结果（高达99％的收率，94％的ee）。其他官能化的衍生物也可以方便地转化。这种不含金属的系统非常方便，实用，并且对空气和湿气不敏感。根据催化剂的晶体结构和NMR光谱分析，提出了一种双功能催化模型来解释不对称过程的起源。

  DOI：

  10.1021/acs.joc.5b00075
• 作为产物：
  描述：

  N-BOC-脒三苯基膦 在 C₂₇H₂₅F₆N₃O₃S 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 72.0h， 生成 (R)-tert-butyl (1-benzyl-3-(nitromethyl)-2-oxoindolin-3-yl)carbamate
  参考文献：
  名称：

  奎宁为基础的串联氮杂-亨利反应环化的三官能有机催化剂：吡咯并吲哚-吡咯烷/哌啶的不对称合成。

  摘要：

  已开发出奎宁衍生的三官能磺酰胺催化剂，用于伊斯兰衍生的酮亚胺和硝基烷-甲磺酸酯的有效不对称有机催化串联aza-Henry反应-环化反应，以合成螺吡咯烷/哌啶-吲哚。传统双功能催化剂的脱甲基结合一个额外的氢键C6'-OH基团对显着的对映选择性起着关键作用。

  DOI：

  10.1021/acs.orglett.7b02150

文献信息

• Asymmetric phase-transfer catalysts bearing multiple hydrogen-bonding donors: Synthesis and application in nitro-Mannich reaction of isatin-derived N-Boc ketimines
  作者：Yuxin Liu、Yu Liu、Jingdong Wang、Zhonglin Wei、Jungang Cao、Dapeng Liang、Yingjie Lin、Haifeng Duan

  DOI：10.1016/j.tetlet.2017.05.022

  日期：2017.6

  A series of bifunctional asymmetric phase-transfer catalysts bearing multiple hydrogen-bonding donors derived from cinchona alkaloids are synthesized, and successfully applied to asymmetric nitro-Mannich of isatin-derived N-Boc ketimines. The products 3-substituted 3-amino-oxindoles were constructed in excellent yields (96–99%) and good enantioselectivities (up to 95% ee).

  合成了一系列由金鸡纳生物碱衍生的带有多个氢键供体的双功能不对称相转移催化剂，并将其成功地应用于衍生自Natin的N-Boc酮亚胺的不对称硝基曼尼希。产品3取代的3-氨基-羟吲哚的构建具有出色的收率（96–99％）和良好的对映选择性（高达95％ee）。
• Organocatalytic enantioselective aza-Henry reaction of ketimines derived from isatins: access to optically active 3-amino-2-oxindoles
  作者：Akshay Kumar、Jasneet Kaur、Swapandeep Singh Chimni、Amanpreet Kaur Jassal

  DOI：10.1039/c4ra00902a

  日期：——

  An organocatalytic asymmetric aza-Henry reaction of ketimines derived from isatins with nitroalkanes has been achieved using Cinchona alkaloid organocatalysts. This method works efficiently with several ketimines to produce a good (up to 82%) yield of the corresponding 3-substituted 3-amino-2-oxindoles with a good (up to 89%) enantiomeric excess.

  使用金鸡纳生物碱有机催化剂已经实现了衍生自靛红的酮亚胺与硝基烷烃的有机催化不对称氮杂-亨利反应。该方法与几种酮亚胺一起有效地起作用，以良好的对映体过量（高达89％）产生相应的3-取代的3-氨基-2-氧吲哚的良好的产率（高达82％）。
• Bis(imidazolidine)pyridine-NiCl₂ Catalyst for Nitro-Mannich Reaction of Isatin-Derived <i>N</i>-Boc Ketimines: Asymmetric Synthesis of Chiral 3-Substituted 3-Amino-2-oxindoles
  作者：Takayoshi Arai、Eri Matsumura、Hyuma Masu

  DOI：10.1021/ol501085y

  日期：2014.5.16

  An (S,S)-diphenyldiamine-derived bis(imidazolidine)-pyridine (PyBidine)-NiCl2 complex catalyzed the nitro-Mannich reaction of isatin-derived N-Boc ketimines to construct a chiral quaternary aminocarbon center at the C3 position of oxindoles in yields of up to 99% with 95% ee.
• Isatin N-protected ketimines with nitromethane catalyzed by chiral binol linked monomeric macrocyclic Cu(II)–salen complex
  作者：Tusharkumar Menapara、Raj kumar Tak、S. Saravanan、Rukhsana I. Kureshy、Noor-ul H. Khan、B. Ganguly、Mrinal Kanti Si

  DOI：10.1016/j.tet.2018.10.001

  日期：2018.12

  Chiral Cu-1B generated in situ was used as an efficient catalyst for the synthesis of beta-nitroamines in high yield (88%) with excellent enantioselectivity (ee up to 99%) at RT in absence of co-catalyst via asymmetric aza-Henry reaction of various isatin derived N-Boc ketimines with nitromethane. This catalytic system did not work well with other nitroalkanes under the above optimized reaction conditions. To examine this catalytic behaviour, quantum chemical DFT calculations were performed with the nucleophiles (CH2NO2- and CH3CHNO2-) for the conversion of la to 2a using macrocyclic Cu-1B complex. The DFT calculated results have shown that the reaction with CH2NO2- is more favourable than the corresponding CH3CHNOy. The calculated activation barriers suggest that the reaction with CH2NO2- is -8.0 kcal/mol energetically favoured than CH3CHNO2-. This catalytic protocol was further used to obtain chiral beta-diamines (a building block for pharmaceuticals) at gram scale. In order to elucidate the reaction mechanism of asymmetric aza Henry reaction kinetic experiments were performed with different concentrations of the catalyst Cu-1B, nitromethane and 1g as the representative substrate. The reaction of isatin N-Boc ketimine was first order with respect to the concentration of the catalyst and the nitromethane but did not depend on the initial concentration of the substrate. A possible mechanism for the aza Henry reaction was proposed. (C) 2018 Elsevier Ltd. All rights reserved.