2-(difluoro(4-(trifluoromethyl)phenyl)methyl)benzo[d]oxazole | 1616729-57-7

• 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: 2-(difluoro(4-(trifluoromethyl)phenyl)methyl)benzo[d]oxazole
• 英文别名: 2-[alpha,alpha-Difluoro-4-(trifluoromethyl)benzyl]benzoxazole；2-[difluoro-[4-(trifluoromethyl)phenyl]methyl]-1,3-benzoxazole
• CAS: 1616729-57-7
• 化学式: C₁₅H₈F₅NO
• 分子量: 313.227
• InChiKey: LAXUHVVDNGKUMT-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：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  26
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-(溴二氟甲基)-1,3-苯并噁唑 、 4-(三氟甲基)苯硼酸频哪醇酯 在 palladium diacetate 、 potassium carbonate 、 正丁基-二(1-金刚烷基)碘化磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 7.0h， 以74%的产率得到2-(difluoro(4-(trifluoromethyl)phenyl)methyl)benzo[d]oxazole
  参考文献：
  名称：

  Heteroaryldifluoromethylation of Organoborons Catalyzed by Palladium: Facile Access to Aryl(Heteroaryl)difluoromethanes

  摘要：

  A first example of Pd-catalyzed heteroaryldifluoromethylation of organoborons with bromodifluoromethylated heteroarenes has been described. The use of phosphine ligand PAd2(n-Bu)·HI is critical for the reaction efficiency. With use of this ligand, a wide range of aryl(heteroaryl)difluoromethanes were obtained with high efficiency. The notable features of this reaction are its broad substrate scope and excellent functional group compatibility, thus providing a facile protocol for application in drug discovery and development.

  DOI：

  10.1021/ol502121m

文献信息

• Nickel-Catalyzed Cross-Coupling of Functionalized Difluoromethyl Bromides and Chlorides with Aryl Boronic Acids: A General Method for Difluoroalkylated Arenes
  作者：Yu-Lan Xiao、Wen-Hao Guo、Guo-Zhen He、Qiang Pan、Xingang Zhang

  DOI：10.1002/anie.201405653

  日期：2014.9.8

  Transition‐metal‐catalyzed difluoroalkylation of aromatics remains challenging despite the importance of difluoroalkylated arenes in medicinal chemistry. Herein, the first successful example of nickel‐catalyzed difluoroalkylation of aryl boronic acids is described. The reaction allows access to a variety of functionalized difluoromethyl bromides and chlorides, and paves the way to highly cost‐efficient

  尽管二氟烷基化芳烃在药物化学中非常重要，但过渡金属催化的芳烃二氟烷基化仍具有挑战性。本文描述了第一个成功的芳基硼酸镍催化二氟烷基化反应的例子。该反应允许获得各种功能化的二氟甲基溴化物和氯化物，并为高成本效益地合成各种二氟烷基化芳烃铺平了道路。该协议的显着特点是它的通用性强，出色的功能基团相容性，低成本的镍催化剂以及克级生产的实用性，从而为药物发现和开发中的应用提供了一种简便的方法。
• Enhancement of Neighbouring-Group Participation in Cu⁰-Promoted Cross-Coupling<i>gem</i>-Difluoromethylenation of Aryl/Alkenyl Halides with 1,3-Azolic Difluoromethyl Bromides
  作者：Haizhen Jiang、Wenjun Lu、Kun Yang、Guobin Ma、Minjun Xu、Jian Li、Jianhua Yao、Wen Wan、Hongmei Deng、Shaoxiong Wu、Shizheng Zhu、Jian Hao

  DOI：10.1002/chem.201402205

  日期：2014.8.4

  3‐azolic (oxa‐, thia‐ or aza‐) difluoromethyl bromides or 2‐bromodifluoromethyl‐1,3‐oxazoline has been developed for the construction of pharmaceutically important gem‐difluoromethylene‐linked twin molecules. The unique π‐conjugated aryl‐fused 1,3‐azolic moiety in difluoromethyl bromide substrates could stabilise the reaction intermediates, which promotes the reactivities, providing facile access to the

  铜（0）促进了未活化的芳基或烯基卤化物与苯并1,3-氮杂（氧杂，硫杂或氮杂）二氟甲基溴化物或2-溴二氟甲基-1,3-恶唑啉的铜（0）促进的直接还原宝石-二氟甲基化反应。为构建药学上重要的宝石-二氟亚甲基连接的双分子而开发。二氟甲基溴基质中独特的π-共轭芳基稠合的1,3-唑基部分可以稳定反应中间体，从而提高反应活性，提供易于获得的交联产物，产率高至优异，并具有显着的官能团耐受性。该反应表现出增强的邻群参与作用。该方法可以为宝石的构建提供新的策略。通过进一步官能化1,3-唑基骨架，使二氟亚甲基连接相同或不相同的孪生药物。
• Heteroaryldifluoromethylation of Organoborons Catalyzed by Palladium: Facile Access to Aryl(Heteroaryl)difluoromethanes
  作者：Yu-Lan Xiao、Bo Zhang、Zhang Feng、Xingang Zhang

  DOI：10.1021/ol502121m

  日期：2014.9.19

  A first example of Pd-catalyzed heteroaryldifluoromethylation of organoborons with bromodifluoromethylated heteroarenes has been described. The use of phosphine ligand PAd2(n-Bu)·HI is critical for the reaction efficiency. With use of this ligand, a wide range of aryl(heteroaryl)difluoromethanes were obtained with high efficiency. The notable features of this reaction are its broad substrate scope and excellent functional group compatibility, thus providing a facile protocol for application in drug discovery and development.