N-[(4-fluorophenyl)(phenyl)methyl]-3-methylpyridin-2-amine | 1370412-42-2

• 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)(phenyl)methyl]-3-methylpyridin-2-amine
• 英文别名: N-[(4-fluorophenyl)-phenylmethyl]-3-methylpyridin-2-amine
• CAS: 1370412-42-2
• 化学式: C₁₉H₁₇FN₂
• 分子量: 292.356
• InChiKey: MHVJEIWHEVEPAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  对氟苄胺 在 [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂ 、 palladium diacetate 、 三甲基乙酸钾 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 甲苯 为溶剂， 反应 40.0h， 生成 N-[(4-fluorophenyl)(phenyl)methyl]-3-methylpyridin-2-amine
  参考文献：
  名称：

  芳基溴和芳基氯用于钌(II)介导的苯甲基胺的直接芳基化

  摘要：

  报道了钌(II)催化的苄胺与芳基卤的 sp3 C-H 键芳基化反应。在本方法中，芳基碘化物以及更重要的是更便宜的芳基溴化物和芳基氯化物可以用作芳基源。此外，该方法不需要在手套箱中进行复杂的操作，并且可以在简单的螺旋盖小瓶中进行。新戊酸钾被证明有利于芳基溴或碘化物作为芳基源的转化，但对于芳基氯则不需要。在后一种情况下，PPh3 的添加导致了高转化率。3-甲基和3-苯基吡啶被确定为定向基团，3-位的取代基代表了高转化率的关键结构特征。引导基团可以在转化后裂解，从而获得二芳基甲基胺。进行了机理研究，并与相关转化的机理报告进行了严格的比较。

  DOI：

  10.1002/ejoc.201300004

文献信息

• Ruthenium(II)-Catalyzed sp³ C–H Bond Arylation of Benzylic Amines Using Aryl Halides
  作者：Navid Dastbaravardeh、Michael Schnürch、Marko D. Mihovilovic

  DOI：10.1021/ol301680v

  日期：2012.7.20

  protocol for the direct arylation of benzylic amines was developed. Employing 3-substituted pyridines as directing groups, arylation was achieved using aryl bromides or aryl iodides as the aryl source. Potassium pivalate proved to be an important additive in this transformation. The arylation took place selectively in the benzylic sp3 position, and no significant competitive sp2 arylation was observed

  建立了钌（II）催化的苄基胺直接芳基化的方案。使用3-取代的吡啶作为指导基团，使用芳基溴化物或芳基碘化物作为芳基源实现芳基化。新戊酸钾被证明是该转化过程中的重要添加剂。芳基化选择性地发生在苄基sp 3位置，没有观察到明显的竞争性sp 2芳基化。观察到少量的丙烯酸化亚胺为副产物。另外，建立了裂解吡啶基的反应条件，使得能够获得双芳基甲胺。
• Mechanistic Investigations and Substrate Scope Evaluation of Ruthenium-Catalyzed Direct sp³ Arylation of Benzylic Positions Directed by 3-Substituted Pyridines
  作者：Navid Dastbaravardeh、Karl Kirchner、Michael Schnürch、Marko D. Mihovilovic

  DOI：10.1021/jo302547q

  日期：2013.1.18

  A highly efficient direct arylation process of benzylic amines with arylboronates was developed that employs Ru catalysis. The arylation takes place with greatest efficiency at the benzylic sp(3) carbon. If the distance to the activating aryl ring is increased, arylation is still possible but the yield drops significantly. Efficiency of the CH activation was found to be significantly increased by use of 3-substituted pyridines as directing groups, which can be removed after the transformation in high yield. Calculation of the energy profile of different rotamers of the substrate revealed that presence of a substituent in the 3-position favors a conformation with the CH2 group adopting a position in closer proximity to the directing group and facilitating C-H insertion. This operationally simple reaction can be carried out in argon atmosphere as well as in air and under neutral reaction conditions, displaying a remarkable functional group tolerance. Mechanistic studies were carried out and critically compared to mechanistic reports of related transformations.