N-(4-fluorophenyl)-5-methylhex-4-enamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-fluorophenyl)-5-methylhex-4-enamide
• 化学式: C₁₃H₁₆FNO
• 分子量: 221.275
• InChiKey: ZTXXLPBBESSSIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(4-fluorophenyl)-5-methylhex-4-enamide 在 Ir(dF(CF₃)ppy)₂(bpy)PF₆ 、 苯硫酚 、 tetrabutylammonium dibutyl phosphate 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以88%的产率得到1-(4-Fluorophenyl)-5-propan-2-ylpyrrolidin-2-one
  参考文献：
  名称：

  Catalytic Olefin Hydroamidation Enabled by Proton-Coupled Electron Transfer

  摘要：

  Here we report a ternary catalyst system for the intramolecular hydroamidation of unactivated olefins using simple N-aryl amide derivatives. Amide activation in these reactions occurs via concerted proton-coupled electron transfer (PCET) mediated by an excited state iridium complex and weak phosphate base to furnish a reactive amidyl radical that readily adds to pendant alkenes. A series of H-atom, electron, and proton transfer events with a thiophenol cocatalyst furnish the product and regenerate the active forms of the photocatalyst and base. Mechanistic studies indicate that the amide substrate can be selectively homolyzed via PCET in the presence of the thiophenol, despite a large difference in bond dissociation free energies between these functional groups.

  DOI：

  10.1021/jacs.5b09671
• 作为产物：
  描述：

  5-甲基-4-己烯酸 、 4-氟苯胺 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以52%的产率得到N-(4-fluorophenyl)-5-methylhex-4-enamide
  参考文献：
  名称：

  Catalytic Olefin Hydroamidation Enabled by Proton-Coupled Electron Transfer

  摘要：

  Here we report a ternary catalyst system for the intramolecular hydroamidation of unactivated olefins using simple N-aryl amide derivatives. Amide activation in these reactions occurs via concerted proton-coupled electron transfer (PCET) mediated by an excited state iridium complex and weak phosphate base to furnish a reactive amidyl radical that readily adds to pendant alkenes. A series of H-atom, electron, and proton transfer events with a thiophenol cocatalyst furnish the product and regenerate the active forms of the photocatalyst and base. Mechanistic studies indicate that the amide substrate can be selectively homolyzed via PCET in the presence of the thiophenol, despite a large difference in bond dissociation free energies between these functional groups.

  DOI：

  10.1021/jacs.5b09671

文献信息

• Catalytic C–N Bond-Forming Reactions Enabled by Proton-Coupled Electron Transfer Activation of Amide N–H Bonds
  作者：Lucas Q. Nguyen、Robert R. Knowles

  DOI：10.1021/acscatal.6b00486

  日期：2016.5.6

  of proton-coupled electron transfer (PCET) to facilitate direct homolytic bond activations of common organic functional groups that are challenging substrates for conventional hydrogen atom transfer catalysts. This perspective details our efforts to develop oxidative PCET platforms for activating the strong N–H bonds of amides, providing catalytic access to synthetically useful amidyl radicals. We

  在过去的三年中，我们的小组对质子偶联电子转移（PCET）促进普通有机官能团的直接均质键活化的能力感兴趣，而普通有机官能团对常规氢原子转移催化剂的底物构成了挑战。该观点详细介绍了我们为开发氧化PCET平台以激活酰胺的强N–H键，为合成有用的酰胺基提供催化途径而做出的努力。我们成功地确定了单电子氧化剂和布朗斯台德碱的兼容组合，尽管它们无法独立激活酰胺底物，但与必要的能级同时伴随通过协调的PCET均化N–H键的作用。所得的酰胺基被用于烯烃碳氨化和加氢酰胺化的新催化方案的开发中。我们还强调了我们的努力，以开发基于PCET的键弱化方案，用于使用酰胺底物的催化共轭胺化反应。在这项工作中，与Ti（III）催化剂配位会显着降低连接的酰胺N–H键的强度，从而使弱H原子受体TEMPO容易发生PCET事件。尽管此讨论的重点是酰胺活化，但我们认为此处介绍的设计参数是通用的，应该为开发PCET催化剂系统提供框架，以
• Catalytic Alkene Carboaminations Enabled by Oxidative Proton-Coupled Electron Transfer
  作者：Gilbert J. Choi、Robert R. Knowles

  DOI：10.1021/jacs.5b05377

  日期：2015.7.29

  N-arylamides (bond dissociation free energies ∼ 100 kcal/mol) via concerted proton-coupled electron transfer (PCET) and mediating efficient carboamination reactions of the resulting amidyl radicals. This manner of PCET activation, which finds its basis in numerous biological redox processes, enables the formal homolysis of a stronger amide N-H bond in the presence of weaker allylic C-H bonds, a selectivity that

  在这里，我们描述了一种由铱光催化剂和弱磷酸盐碱组成的双催化剂体系，该体系能够通过协同质子耦合电子转移（PCET）选择性地均化 N-芳基酰胺的 NH 键（键解离自由能 ~ 100 kcal/mol） ) 并介导所得酰胺基自由基的有效碳胺化反应。这种 PCET 活化方式在众多生物氧化还原过程中找到了基础，它能够在较弱的烯丙基 CH 键存在下对较强的酰胺 NH 键进行形式均裂，这种选择性在常规分子 H 原子受体中并不常见。此外，这种转化可以从简单的酰胺原料中获得广泛的结构复杂的杂环。设计，合成范围，
• Photoredox-Catalyzed Oxidation of Anions for the Atom-Economical Hydro-, Amido-, and Dialkylation of Alkenes
  作者：Katherine C. Forbes、Anne Marie Crooke、Yuri Lee、Masamu Kawada、Kian M. Shamskhou、Rachel A. Zhang、Jeffrey S. Cannon

  DOI：10.1021/acs.joc.1c03055

  日期：2022.3.4

  method to generate free radical intermediates in organic synthesis. This report describes the use of photoredox catalysis to directly oxidize common nucleophilic anions to access electrophilic 1,3-dicarbonyl and amidyl radical intermediates. First, conjugate bases of 1,3-dicarbonyls were oxidized to neutral radical species for intramolecular hydro- and dialkylation of alkenes. This overall redox-neutral

  光氧化还原催化已成为有机合成中产生自由基中间体的有效方法。本报告描述了使用光氧化还原催化直接氧化常见的亲核阴离子以获得亲电子 1,3-二羰基和酰胺基自由基中间体。首先，1,3-二羰基的共轭碱基被氧化成中性自由基，用于烯烃的分子内加氢和二烷基化。这种整体氧化还原中性工艺以优异的收率（高达 96%）提供了环戊酮产品。范围包括各种苯乙烯自由基受体和具有新形成的邻位季碳的产品。然后将该过程扩展到通过通过N进行的烯烃酰胺基烷基化来合成吡咯烷酮-芳基酰胺基自由基中间体，产率高（高达 85%）。这些反应的特点是条件温和、原子经济性高，并且没有化学计量的副产物。机械和计算研究支持逐步质子耦合电子转移机制，其中“借电子”光催化剂氧化阴离子并在成键后还原苄基自由基。
• Catalytic Olefin Hydroamidation Enabled by Proton-Coupled Electron Transfer
  作者：David C. Miller、Gilbert J. Choi、Hudson S. Orbe、Robert R. Knowles

  DOI：10.1021/jacs.5b09671

  日期：2015.10.28

  Here we report a ternary catalyst system for the intramolecular hydroamidation of unactivated olefins using simple N-aryl amide derivatives. Amide activation in these reactions occurs via concerted proton-coupled electron transfer (PCET) mediated by an excited state iridium complex and weak phosphate base to furnish a reactive amidyl radical that readily adds to pendant alkenes. A series of H-atom, electron, and proton transfer events with a thiophenol cocatalyst furnish the product and regenerate the active forms of the photocatalyst and base. Mechanistic studies indicate that the amide substrate can be selectively homolyzed via PCET in the presence of the thiophenol, despite a large difference in bond dissociation free energies between these functional groups.