tert-butyl 3-(3,4-dimethoxybenzyl)-2-oxoindoline-1-carboxylate | 1229652-52-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: tert-butyl 3-(3,4-dimethoxybenzyl)-2-oxoindoline-1-carboxylate
• CAS: 1229652-52-1
• 化学式: C₂₂H₂₅NO₅
• 分子量: 383.444
• InChiKey: RGDFDNIVSRBEFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.31
• 重原子数：
  28.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  65.07
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(3,4-dimethoxybenzyl)-2-oxoindoline-1-carboxylate 在 四丁基溴化铵 、 sodium hydride 、 potassium carbonate 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 82.17h， 生成
  参考文献：
  名称：

  A facile and efficient synthesis of hexahydro-1H-pyrido[2,3-b]indol-2-one scaffolds via a sequential Michael addition/amidation/reductive cyclization process

  摘要：

  A new methodology was developed for the synthesis of hexahydro-1H-pyrido[2,3-b]indol-2-one scaffolds via a sequential Michael addition/amidation/reductive cyclization process. A wide variety of products bearing a hexahydro-1H-pyrido[2,3-b]indol-2-one core with varying degrees of substitution around it, which is a key structural skeleton found in a large number of biologically active natural products and pharmaceutical compounds, were obtained smoothly with high efficiency (up to overall yield of 67%). Furthermore, their biological activities have been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells k562 by the MU-based assays, using the commercially available standard drug Cisplatin as a positive control. These results suggested there is a trend that lipophilic groups improve the potency, and also suggested a carbonyl moiety located in the hexahydro-1H-pyrido[2,3-b]indol-2-one scaffolds is beneficial for the activity. The results also demonstrated that most of the compounds showed considerable cytotoxicities to these three cell lines K562, A549 and PC-3, and that hexahydro-1H-pyrido[2,3-b]indol-2-one scaffolds may be potential leads for further antitumor activity screenings. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2015.10.039

文献信息

• Amino-Indanol-Catalyzed Asymmetric Michael Additions of Oxindoles to Protected 2-Amino-1-nitroethenes for the Synthesis of 3,3′-Disubstituted Oxindoles Bearing α,β-Diamino Functionality
  作者：Xiong-Li Liu、Zhi-Jun Wu、Xi-Lin Du、Xiao-Mei Zhang、Wei-Cheng Yuan

  DOI：10.1021/jo2004378

  日期：2011.5.20

  An organocatalytic asymmetric Michael addition reaction of 3-substituted oxindoles to protected 2-amino-1-nitroethenes has been developed. The reaction is catalyzed by a simple and readily available amino-indanol derivative and affords the desired products in very high yields (up to 99%) with excellent diastereoselectivities (up to >99:1) and very good enantioselectivities (up to 90%). Significantly

  已经开发出3-取代的羟吲哚与被保护的2-氨基-1-硝基乙烯的有机催化不对称迈克尔加成反应。该反应由一种简单易得的氨基氨基茚满醇衍生物催化，以非常高的非对映选择性（高达> 99：1）和非常好的对映选择性（高达90％）以非常高的收率（高达99％）提供所需的产物。 。重要的是，这项研究为构建带有α，β-二氨基官能团的3，3′-二取代的羟吲哚以及邻近的手性季/叔立体中心提供了一种通用的催化方法。该协议的潜在效用也已通过克级反应和产物的多用途转化得到了证明。此外，根据全面的实验结果和其中一种迈克尔加合物的绝对构型，
• Highly regioselective synthesis of 3-alkenyl-oxindole ring-fused 3,3′-disubstituted oxindoles via direct gamma-substitution of Morita–Baylis–Hillman carbonates of isatins with 3-substituted oxindoles
  作者：Ting-Ting Feng、Xuan Huang、Xiong-Li Liu、De-Hong Jing、Xiong-Wei Liu、Feng-Ming Guo、Ying Zhou、Wei-Cheng Yuan

  DOI：10.1039/c4ob01523a

  日期：——

  The first phase transfer-catalysed direct γ-substitution of Morita–Baylis–Hillman carbonates of isatins with 3-substituted oxindoles has been developed, which affords 3-alkenyl-oxindole ring-fused 3,3′-disubstituted oxindoles in up to 83% yield under mild reaction conditions. Furthermore, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer

  已经开发出第一批经相转移催化的森田的Bayes-Hillman碳酸异丁酯碳酸酯与3-取代的羟吲哚的直接γ取代反应，该化合物可提供高达83％的3-烯基-羟吲哚环稠合的3,3'-二取代的羟吲哚。在温和的反应条件下收率。此外，使用基于MTT的检测方法，以市售标准药物顺铂为阳性对照，通过针对人前列腺癌细胞PC-3和人白血病细胞K562的体外评估，初步证明了其生物学活性。令人欣慰的是，化合物3aa，3ba和3ca对人前列腺癌细胞（PC-3）的体外抑制活性与顺铂相当。更重要的是，3ba对人白血病细胞K562也具有良好的抑制作用。这些结果表明3-烯基-羟吲哚环稠合的3，3′-二取代的羟吲哚类似物可能是用于进一步生物学筛选的潜在先导化合物。
• Asymmetric Allylic Alkylation with Deconjugated Carbonyl Compounds: Direct Vinylogous Umpolung Strategy
  作者：Guang‐Yao Ran、Xing‐Xing Yang、Jing‐Fei Yue、Wei Du、Ying‐Chun Chen

  DOI：10.1002/anie.201903478

  日期：2019.7

  conditions. In cooperation with a chiral‐phosphonium‐based phase‐transfer catalyst, the asymmetric direct oxidative allylic alkylations of 3‐substituted oxindoles are furnished under O2 atmosphere. The γ‐ or even remote ϵ‐regioselective alkylation products, with substantial substituents, are delivered with excellent enantioselectivity, and can be further used to access diverse chiral spirocyclic architectures

  针对无共轭羰基化合物，开发了一种原子经济且高效的乙烯基类化合物策略，该策略可在无配体条件下与Pd（OAc）2生成电子不足的π-烯丙基铝配合物。与手性phosph基相转移催化剂配合使用，在O 2气氛下提供了3个取代的羟吲哚的不对称直接氧化烯丙基烷基化反应。具有大量取代基的γ或什至偏远的ϵ区域选择性烷基化产物具有出色的对映选择性，可进一步用于有效地访问各种手性螺环结构。可以类似地使用Mukaiyama二烯醇甲硅烷基醚，这表明当前的活性π-烯丙基铝物种是Pd互变异构化的结果II-二壬酸酯中间体。
• Organocatalytic Asymmetric Conjugate Addition of 3-Monosubstituted Oxindoles to (<i>E</i>)-1,4-Diaryl-2-buten-1,4-diones: A Strategy for the Indirect Enantioselective Furanylation and Pyrrolylation of 3-Alkyloxindoles
  作者：Yu-Hua Liao、Xiong-Li Liu、Zhi-Jun Wu、Xi-Lin Du、Xiao-Mei Zhang、Wei-Cheng Yuan

  DOI：10.1002/chem.201103293

  日期：2012.5.21

  3′‐disubstituted oxindoles—3‐furanyl‐ and 3‐pyrrolyl‐3‐alkyl‐oxindoles—in high yields and good enantioselectivities. Notably, the studies presented here sufficiently confirm that this two‐step strategy of sequential conjugate addition/Paal–Knorr cyclization is not only an attractive method for the indirect enantioselective heteroarylation of 3‐alkyloxindoles, but also opens up new avenues toward asymmetric synthesis

  3-单取代的羟吲哚的不对称共轭加成范围为（E）描述了由市售的辛可宁催化的1,4-二芳基-2-丁烯-1,4-二酮。这种有机催化不对称反应提供了范围广的3,3'-二取代的羟吲哚，这些化合物包含1,4-二羰基部分以及附近的季铵和叔立体中心，收率高至优异（高达98％），并具有出色的非对映异构体和中高对映体比例（分别高达99：1和95：5）。随后，在不同的Paal–Knorr条件下，所得迈克尔加合物中1,4-二羰基部分的环化产生了两种新型的3,3'-二取代的羟吲哚——3-呋喃基和3-吡咯基-3-烷基-氧吲哚-高收率和良好的对映选择性。尤其，
• Organocatalytic Enantioselective Hydroxymethylation of Oxindoles with Paraformaldehyde as C1 Unit
  作者：Xiong-Li Liu、Yu-Hua Liao、Zhi-Jun Wu、Lin-Feng Cun、Xiao-Mei Zhang、Wei-Cheng Yuan

  DOI：10.1021/jo100769n

  日期：2010.7.16

  A bifunctional thiourea-tertiary amine-catalyzed asymmetric hydroxymethylation of 3-substituted oxindoles using paraformaldehyde as the C1 unit was developed. A wide scope of oxindoles, bearing C3 sterically congested quaternary carbon centers, were smoothly obtained in good to excellent yields (up to 99%) and high enantioselectivities (up to 91% ee) under mild reaction conditions. A more significant feature of this approach employs cheap and readily available paraformaldehyde as a hydroxymethylation Cl unit, which is activated by chiral bifunctional thiourea organocatalysts.