tert-butyl (S)-(1-methyl-3-(nitromethyl)-2-oxoindolin-3-yl)carbamate | 1606996-79-5

• 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: tert-butyl (S)-(1-methyl-3-(nitromethyl)-2-oxoindolin-3-yl)carbamate
• 英文别名: tert-butyl N-[(3S)-1-methyl-3-(nitromethyl)-2-oxoindol-3-yl]carbamate
• CAS: 1606996-79-5
• 化学式: C₁₅H₁₉N₃O₅
• 分子量: 321.333
• InChiKey: BVCRPLTWLQZAIY-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  tert-butyl (S)-(1-methyl-3-(nitromethyl)-2-oxoindolin-3-yl)carbamate 在 盐酸 、 sodium tetrahydroborate 、 nickel(II) chloride hexahydrate 作用下， 以 甲醇 、 乙醚 为溶剂， 生成 (S)-3-amino-3-(aminoethyl)-1-methylindolin-2-one
  参考文献：
  名称：

  可回收手性Cu(II)大环salen配合物催化靛红衍生N-Boc酮亚胺的对映选择性氮杂-亨利反应及其在β-二胺合成中的应用

  摘要：

  摘要 原位生成的可回收手性 Cu(II) 大环Salen 配合物 Cu(II)-7 在室温下高效催化各种靛红衍生的 N-Boc 酮亚胺与硝基甲烷作为亲核试剂的不对称氮杂亨利反应，得到高产率 (88%) β-硝基胺具有出色的手性诱导（ee，高达 99%），并具有六倍催化剂可回收性的额外优势。该催化体系还可以与硝基乙烷和硝基戊烷很好地协同工作，以中等收率提供相应的产物，并对主要非对映异构体具有高对映选择性。该协议还用于通过 N-Boc 酮亚胺 (1b) 的不对称氮杂-亨利反应合成对映体纯 (S)-β-二胺，该反应分为两步，产率高，对映选择性高。

  DOI：

  10.1016/j.molcata.2016.05.021
• 作为产物：
  描述：

  硝基甲烷 、 tert-butyl 1-methyl-2-oxoindolin-3-ylidenecarbamate 在 (4R,9R,36R,41R)-14,31,46,63-tetratert-butyl-18,21,24,27,50,53,56,59-octaoxa-3,10,35,42-tetrazaheptacyclo[59.3.1.112,16.129,33.144,48.04,9.036,41]octahexaconta-1(64),2,10,12,14,16(68),29(67),30,32,34,42,44,46,48(66),61(65),62-hexadecaene-13,32,45,64-tetrol 、 Cu(OTf)₂*xH₂O 作用下， 以 四氢呋喃 为溶剂， 反应 30.0h， 以80%的产率得到tert-butyl (S)-(1-methyl-3-(nitromethyl)-2-oxoindolin-3-yl)carbamate
  参考文献：
  名称：

  可回收手性Cu(II)大环salen配合物催化靛红衍生N-Boc酮亚胺的对映选择性氮杂-亨利反应及其在β-二胺合成中的应用

  摘要：

  摘要 原位生成的可回收手性 Cu(II) 大环Salen 配合物 Cu(II)-7 在室温下高效催化各种靛红衍生的 N-Boc 酮亚胺与硝基甲烷作为亲核试剂的不对称氮杂亨利反应，得到高产率 (88%) β-硝基胺具有出色的手性诱导（ee，高达 99%），并具有六倍催化剂可回收性的额外优势。该催化体系还可以与硝基乙烷和硝基戊烷很好地协同工作，以中等收率提供相应的产物，并对主要非对映异构体具有高对映选择性。该协议还用于通过 N-Boc 酮亚胺 (1b) 的不对称氮杂-亨利反应合成对映体纯 (S)-β-二胺，该反应分为两步，产率高，对映选择性高。

  DOI：

  10.1016/j.molcata.2016.05.021

文献信息

• Highly enantioselective aza-Henry reaction with isatin <i>N</i>-Boc ketimines
  作者：Melireth Holmquist、Gonzalo Blay、José R. Pedro

  DOI：10.1039/c4cc04051a

  日期：——

  A highly enantioselective aza-Henry reaction with isatin N-Boc ketimines using a Cu(II)-BOX complex as a catalyst is described. The reaction, which does not require protection of the N1 atom, provides the corresponding nitroamines bearing a quaternary stereocentre with high yields and enantiomeric excesses (up to 99.9%).

  描述了使用Cu（II）-BOX配合物作为催化剂与靛红N-Boc酮亚胺的高度对映选择性氮杂-亨利反应。该反应不需要保护N 1原子，从而提供了带有季立体中心的相应硝胺，具有高收率和对映体过量（高达99.9％）。
• 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）。
• 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.
• Recyclable chiral Cu(II) macrocyclic salen complex catalyzed enantioselective aza-Henry reaction of isatin derived N-Boc ketimines and its application for the synthesis of β-diamine
  作者：Tusharkumar Menapara、Manoj K. Choudhary、Rajkumar Tak、Rukhsana I. Kureshy、Noor-ul H. Khan、Sayed H.R. Abdi

  DOI：10.1016/j.molcata.2016.05.021

  日期：2016.9

  Abstract Recyclable chiral Cu(II) macrocyclic salen complex Cu(II)-7 generated in situ efficiently catalyzed asymmetric aza-Henry reaction of various isatin derived N-Boc ketimines with nitromethane as nucleophile at RT to give a high yield (88%) of β-nitro amines with excellent chiral induction (ee, up to 99%) with the added advantage of six times catalyst recyclability. This catalytic system also

  摘要 原位生成的可回收手性 Cu(II) 大环Salen 配合物 Cu(II)-7 在室温下高效催化各种靛红衍生的 N-Boc 酮亚胺与硝基甲烷作为亲核试剂的不对称氮杂亨利反应，得到高产率 (88%) β-硝基胺具有出色的手性诱导（ee，高达 99%），并具有六倍催化剂可回收性的额外优势。该催化体系还可以与硝基乙烷和硝基戊烷很好地协同工作，以中等收率提供相应的产物，并对主要非对映异构体具有高对映选择性。该协议还用于通过 N-Boc 酮亚胺 (1b) 的不对称氮杂-亨利反应合成对映体纯 (S)-β-二胺，该反应分为两步，产率高，对映选择性高。