2,2,6,6-tetramethyl-1-(3,3,3-trifluoro-1-phenylpropoxy)piperidine | 1401714-03-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2,2,6,6-tetramethyl-1-(3,3,3-trifluoro-1-phenylpropoxy)piperidine
• 英文别名: 2,2,6,6-Tetramethyl-1-(3,3,3-trifluoro-1-phenylpropoxy)piperidine
• CAS: 1401714-03-1
• 化学式: C₁₈H₂₆F₃NO
• 分子量: 329.406
• InChiKey: KIJAHFPJGBWGOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,2,6,6-tetramethyl-1-(3,3,3-trifluoro-1-phenylpropoxy)piperidine 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以92%的产率得到(E)-3,3,3-trifluoro-1-phenylpropene
  参考文献：
  名称：

  Hydroxylamine‐Mediated C(sp2)−H Trifluoromethylation of Terminal Alkenes

  摘要：

  Introduction of the trifluoromethyl (CF3) group into organic compounds has garnered substantial interest because of its significant role in pharmaceuticals and agrochemicals. Here, we report a hydroxylamine‐mediated radical process for C(sp2)−H trifluoromethylation of terminal alkenes. The reaction shows good reactivity, impressive E/Z selectivity (up to > 20:1), and broad functional group compatibility. Expansion of this approach to perfluoroalkylation and late‐stage trifluoromethylation of bioactive molecules demonstrates its promising application potential. Mechanistic studies suggest that the reaction follows a radical addition and subsequent elimination pathway.

  DOI：

  10.1002/chem.202400995
• 作为产物：
  描述：

  2,2,6,6-四甲基哌啶氧化物 在 萘 、 sodium 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 2,2,6,6-tetramethyl-1-(3,3,3-trifluoro-1-phenylpropoxy)piperidine
  参考文献：
  名称：

  通过实用方法 确定将三氟甲基自由基加到各种烯烃中的速率常数†

  摘要：

  介绍了一种应用竞争动力学测定三氟甲基自由基加成烯烃的速率常数的简单实用方法。在动力学实验中，通过在TEMPO和π受体存在下用TEMPONa进行SET还原，由市售的高价碘-CF 3试剂（Togni-reagent）原位生成三氟甲基自由基。由TEMPOCF 3和CF 3的相对比例形成加成产物，可轻松确定为19通过F-NMR光谱，可以计算出将三氟甲基自由基加到π-受体上的速率常数。该实用方法还适用于测量CF 3 CF 2自由基加成反应中记录的将其他全氟烷基自由基加成至烯烃的速率常数。

  DOI：

  10.1039/c5ob02210j

文献信息

• Enantioselective Trifluoromethylalkynylation of Alkenes via Copper-Catalyzed Radical Relay
  作者：Liang Fu、Song Zhou、Xiaolong Wan、Pinhong Chen、Guosheng Liu

  DOI：10.1021/jacs.8b07436

  日期：2018.9.5

  A novel enantioselective copper-catalyzed trifluoromethylalkynylation of styrenes, proceeding through a radical relay process, is described herein, which affords structurally diverse CF3-containing propargylic compounds in good yield with excellent enantioselectivities under very mild conditions. In addition, the reaction features wide substrate scope and good functional group tolerance. Moreover,

  本文描述了通过自由基中继过程进行的苯乙烯的新型对映选择性铜催化三氟甲基炔基化，其在非常温和的条件下以良好的收率和优异的对映选择性提供结构多样的含 CF3 炔丙基化合物。此外，该反应底物范围广，官能团耐受性好。此外，三氟甲基炔基化产物可以很容易地转化为合成有用的手性末端炔烃、丙二烯、Z-烯烃以及CF3修饰的非甾体抗炎药。
• Copper-Catalyzed Intermolecular Trifluoromethylthiocyanation of Alkenes: Convenient Access to CF₃-Containing Alkyl Thiocyanates
  作者：Zhaoli Liang、Fei Wang、Pinhong Chen、Guosheng Liu

  DOI：10.1021/acs.orglett.5b00939

  日期：2015.5.15

  selective and efficient approach for the direct trifluoromethylthiocyanation of alkenes has been developed using trimethylsilyl isothiocyanate (TMSNCS) as the thiocyanating agent and Togni reagent as the CF3 source in the presence of copper(I) catalyst. Both activated and unactivated alkenes work well to deliver various CF3-containing thiocyanates.

  在铜（I）催化剂存在下，使用三甲基甲硅烷基异硫氰酸酯（TMSNCS）作为硫氰酸化剂和Togni试剂作为CF 3源，已经开发出了一种用于烯烃直接三氟甲基硫氰化的高选择性和高效方法。活化的和未活化的烯烃都可以很好地递送各种含CF 3的硫氰酸酯。
• Transition-Metal-Free Trifluoromethylaminoxylation of Alkenes
  作者：Yi Li、Armido Studer

  DOI：10.1002/anie.201202623

  日期：2012.8.13

  No transition metal! Fluorinated hypervalent‐iodine reagents react with TEMPONa in the presence of an alkene under mild conditions to give the corresponding perfluoroalkylaminoxylation products. These radical addition/trapping reactions occur with high stereoselectivity using commercially available reagents, and the product alkoxyamines are readily transformed into the corresponding alcohols.

  没有过渡金属！在烯烃存在下，氟化的高价碘试剂在温和的条件下与TEMPONa反应，得到相应的全氟烷基氨基木糖基化产物。这些自由基加成/捕集反应使用市售试剂高立体选择性发生，并且该产物烷氧基胺易于转化成相应的醇。
• Copper-Catalyzed Intermolecular Trifluoromethylarylation of Alkenes: Mutual Activation of Arylboronic Acid and CF₃⁺ Reagent
  作者：Fei Wang、Dinghai Wang、Xin Mu、Pinhong Chen、Guosheng Liu

  DOI：10.1021/ja504458j

  日期：2014.7.23

  A novel copper-catalyzed intermolecular trifluoromethylarylation of alkenes is developed using less active ether-type Togni's reagent under mild reaction conditions. Various alkenes and diverse arylboronic acids are compatible with these conditions. Preliminary mechanistic studies reveal that a mutual activation process between arylboronic acid and CF3+ reagent is essential. In addition, the reaction might involve a rate-determining transmetalation, and the final aryl C-C bond is derived from reductive elimination of the aryl(alkyl)Cu(III) intermediate.
• Determination of rate constants for trifluoromethyl radical addition to various alkenes via a practical method
  作者：M. Hartmann、Y. Li、A. Studer

  DOI：10.1039/c5ob02210j

  日期：——

  CF3-addition product formed, which is readily determined by 19F-NMR spectroscopy, rate constants for trifluoromethyl radical addition to the π-acceptor can be calculated. The practical method is also applicable to measure rate constants for the addition of other perfluoroalkyl radicals to alkenes as documented for CF3CF2-radical addition reactions.

  介绍了一种应用竞争动力学测定三氟甲基自由基加成烯烃的速率常数的简单实用方法。在动力学实验中，通过在TEMPO和π受体存在下用TEMPONa进行SET还原，由市售的高价碘-CF 3试剂（Togni-reagent）原位生成三氟甲基自由基。由TEMPOCF 3和CF 3的相对比例形成加成产物，可轻松确定为19通过F-NMR光谱，可以计算出将三氟甲基自由基加到π-受体上的速率常数。该实用方法还适用于测量CF 3 CF 2自由基加成反应中记录的将其他全氟烷基自由基加成至烯烃的速率常数。