methyl 3,3-bis(1-methyl-1H-indol-3-yl)propanoate | 1338221-45-6

• 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: methyl 3,3-bis(1-methyl-1H-indol-3-yl)propanoate
• 英文别名: Methyl 3,3-bis(1-methylindol-3-yl)propanoate；methyl 3,3-bis(1-methylindol-3-yl)propanoate
• CAS: 1338221-45-6
• 化学式: C₂₂H₂₂N₂O₂
• 分子量: 346.429
• InChiKey: HTOIEYKTBHJFKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  36.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl 3,3-bis(1-methyl-1H-indol-3-yl)propanoate 、 (3,3-二乙氧基-1-丙烯-2-基)苯 在 对甲苯磺酸 作用下， 反应 3.0h， 生成 methyl 5-methyl-7-phenyl-5,8-dihydrocyclohepta[b]indole-9-carboxylate
  参考文献：
  名称：

  布朗斯台德酸催化级联环化：环庚[b]吲哚衍生物发散合成的有效策略

  摘要：

  基于 BIM 向乙烯基吲哚的关键转化，建立了一种有效的酸催化三组分级联策略，以合成一种特殊的支架，即苯基取代的二氢环庚二[ b ]吲哚羧酸盐。乙烯基吲哚中间体可作为 1,4-双亲核试剂，可被阿托醛缩醛捕获以构建二苯基取代的二氢环庚二[ b ]吲哚。还建立了 2-芳基-3,4-二氢吡喃与 2,3-未取代的吲哚的 [5 + 2] 环化反应，这为获得四氢环庚[ b ]吲哚提供了另一种途径。容易获得的材料、廉价的无金属催化剂、环保溶剂和不同的合成方法确保了这些方法具有实际吸引力。

  DOI：

  10.1039/d2gc02072f
• 作为产物：
  描述：

  吲哚 在 tetrakis(acetonitrile)palladium(II) bis(tetrafluoroborate) 、 sodium hydride 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 15.5h， 生成 methyl 3,3-bis(1-methyl-1H-indol-3-yl)propanoate
  参考文献：
  名称：

  Pd-Catalyzed Direct Coupling of Indoles with Carbon Monoxide and Alkynes: Selective Synthesis of Linear α,β-Unsaturated Ketones

  摘要：

  A new strategy is described for the direct coupling of indoles with CO and alkynes to generate alpha,beta-unsaturated ketones. This procedure, employing Xantphos and Pd(CH3CN)(4)(BF4)(2), is attractive from both environmental and operational points of view and adds value to the method for the carbonylation of alkynes by using carbon nucleophiles and affording linear regioselectivity.

  DOI：

  10.1021/ol400722h

文献信息

• Non-redox metal ion promoted oxidative coupling of indoles with olefins by the palladium(<scp>ii</scp>) acetate catalyst through dioxygen activation: experimental results with DFT calculations
  作者：Sicheng Zhang、Zhuqi Chen、Shuhao Qin、Chenlin Lou、Ahmed M. Senan、Rong-Zhen Liao、Guochuan Yin

  DOI：10.1039/c6ob00401f

  日期：——

  Pd(II)-catalyzed oxidative coupling previously. Detailed investigations revealed that the reaction proceeds by heterobimetallic Pd(II)/Sc(III)-catalyzed oxidative coupling of an indole with an olefin followed by Sc(III)-catalyzed addition with a second indole molecule. DFT calculations disclosed that the formation of heterobimetallic Pd(II)/Sc(III) species substantially decreases the C–H bond activation

  近几十年来，通过C–H键活化作用开发新的催化技术以合成多功能药物引起了人们的广泛关注。这项工作为Pd（II）催化的C–H键活化引入了一种新的催化剂设计策略，其中作为路易斯酸的非氧化还原金属离子起着重要的作用。在使用双氧将吲哚与烯烃进行氧化偶合时，发现单独的Pd（OAc）2作为催化剂在环境温度下非常缓慢，这会降低烯化产物的产率，而向Pd中添加非氧化还原金属离子（ OAc）2大大提高了其催化效率。特别是，它提供了双（吲哚基）甲烷衍生物作为主要产物，这是以前不能通过Pd（II）催化的氧化偶联合成的一类药理分子。详细的研究表明，该反应通过吲哚与烯烃的异双金属Pd（II）/ Sc（III）催化的氧化偶联而进行，然后通过Sc（III）催化的第二个吲哚分子进行加成反应。DFT计算表明，异双金属Pd（II）/ Sc（III）的形成）物质会大大降低C–H键活化能垒，并将速率确定步骤从吲哚的C–H键活化转移到
• TFA-catalyzed C–N bond activation of enamides with indoles: efficient synthesis of 3,3-bisindolylpropanoates and other bisindolylalkanes
  作者：Hai-Yan Xu、You Zi、Xiao-Ping Xu、Shun-Yi Wang、Shun-Jun Ji

  DOI：10.1016/j.tet.2012.11.098

  日期：2013.2

  An efficient TFA-catalyzed cleavage of C-N bonds in alkylation of indoles by tertiary enamides was described. A variety of bisindolylalkane derivatives, especially 3,3-bisindolylpropanoates, were expeditiously synthesized in good yields. (c) 2012 Elsevier Ltd. All rights reserved.
• Regioselective synthesis of 3,3-bis(indolyl)propanoic acid derivatives by iron(III)-catalyzed hydroarylation of propynoic acid derivatives with indoles
  作者：Md. Shahajahan Kutubi、Tsugio Kitamura

  DOI：10.1016/j.tet.2011.08.051

  日期：2011.10

  Intermolecular hydroarylation of propynoic acid and its esters with indoles proceeded efficiently in acetic acid under a catalytic system of FeCl3/3AgOTf and afforded the corresponding 3,3-bis(indol-3yl) propanoic acids and their esters in high yields. In the case of 2-methylindole, 3-indolylacrylic acid and its ethyl ester were obtained in high yields. This iron-catalyzed hydroarylation showed a high regioselectivity at the 3-position of indoles and a high utility for the synthesis of bis(indol-3-yl) compounds, which are important for biological and pharmaceutical fields. (C) 2011 Elsevier Ltd. All rights reserved.
• Pd-Catalyzed Direct Coupling of Indoles with Carbon Monoxide and Alkynes: Selective Synthesis of Linear α,β-Unsaturated Ketones
  作者：Fanlong Zeng、Howard Alper

  DOI：10.1021/ol400722h

  日期：2013.4.19

  A new strategy is described for the direct coupling of indoles with CO and alkynes to generate alpha,beta-unsaturated ketones. This procedure, employing Xantphos and Pd(CH3CN)(4)(BF4)(2), is attractive from both environmental and operational points of view and adds value to the method for the carbonylation of alkynes by using carbon nucleophiles and affording linear regioselectivity.
• Brønsted acid-catalyzed cascade cyclization: an efficient strategy for divergent synthesis of cyclohepta[<i>b</i>]indole derivatives
  作者：Shaomin Chen、Zhiyan Chen、Tianjian Zhang、Bo Zhao、Bo You、Minghao Li、Yanlong Gu

  DOI：10.1039/d2gc02072f

  日期：——

  dihydrocyclohepta[b]indole carboxylate. The vinylindole intermediates worked as 1,4-bisnucleophiles and could be trapped by atropaldehyde acetals to construct diphenyl-substituted dihydrocyclohepta[b]indoles. A [5 + 2] cyclization of 2-aryl-3,4-dihydropyrans with 2,3-unsubstituted indoles was also established, which provided another route to access tetrahydrocyclohepta[b]indoles. Readily available materials

  基于 BIM 向乙烯基吲哚的关键转化，建立了一种有效的酸催化三组分级联策略，以合成一种特殊的支架，即苯基取代的二氢环庚二[ b ]吲哚羧酸盐。乙烯基吲哚中间体可作为 1,4-双亲核试剂，可被阿托醛缩醛捕获以构建二苯基取代的二氢环庚二[ b ]吲哚。还建立了 2-芳基-3,4-二氢吡喃与 2,3-未取代的吲哚的 [5 + 2] 环化反应，这为获得四氢环庚[ b ]吲哚提供了另一种途径。容易获得的材料、廉价的无金属催化剂、环保溶剂和不同的合成方法确保了这些方法具有实际吸引力。