化学学报 ›› 2019, Vol. 77 ›› Issue (9): 884-888.DOI: 10.6023/A19060220 上一篇    下一篇

所属专题: 有机自由基化学

研究通讯

铜催化苯甲酰亚胺高烯丙酯的分子内胺化全氟烷基化反应

张衡, 牟学清, 陈弓*(), 何刚*()   

  1. 南开大学化学学院 元素有机化学国家重点实验室 天津 300071
  • 收稿日期:2019-06-18 出版日期:2019-09-15 发布日期:2019-08-13
  • 通讯作者: 陈弓,何刚 E-mail:gongchen@nankai.edu.cn;hegang@nankai.edu.cn
  • 基金资助:
    项目受国家自然科学基金(Nos.21672105);项目受国家自然科学基金(21702109);项目受国家自然科学基金(21890722);天津市自然科学基金(Nos.17JCYBJC19700);天津市自然科学基金(18JCZDJC32800);南开大学中央高校基本科研业务费专项资金资助(No.63161122)

Copper-catalyzed Intramolecular Aminoperfluoroalkylation Reaction of O-Homoallyl Benzimidates

Zhang, Heng, Mou, Xueqing, Chen, Gong*(), He, Gang*()   

  1. State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071
  • Received:2019-06-18 Online:2019-09-15 Published:2019-08-13
  • Contact: Chen, Gong,He, Gang E-mail:gongchen@nankai.edu.cn;hegang@nankai.edu.cn
  • Supported by:
    Project supported by the National Natural Science Foundation of China(Nos.21672105);Project supported by the National Natural Science Foundation of China(21702109);Project supported by the National Natural Science Foundation of China(21890722);Natural Science Foundation of Tianjin(Nos.17JCYBJC19700);Natural Science Foundation of Tianjin(18JCZDJC32800);the Fundamental Research Funds for the Central Universities (Nankai University)(No.63161122)

报道了铜催化苯甲酰亚胺高烯丙酯底物的分子内胺化全氟烷基化反应. 该反应以全氟碘代烷为全氟烷基化试剂, 醋酸铜为催化剂, 邻菲啰啉为配体, 在醋酸银存在下以中等的收率实现苯甲酰亚胺高烯丙酯底物末端双键的胺化全氟烷基化, 最终生成1,3-噁嗪类分子. 多种官能团取代的苯甲酰亚胺高烯丙酯和具有不同碳链长度的全氟碘代烷烃都能适用于该反应, 为多氟烷基取代的1,3-噁嗪类化合物的合成提供了一种简洁的方法. 多氟烷基取代的1,3-噁嗪类化合物还可在温和条件下高效转化为γ氨基醇衍生物. 初步的机理研究证明该反应经历了全氟烷基自由基对碳碳双键的亲电加成, 之后苯甲酰亚胺基团作为分子内亲核性胺源经历分子内亲核取代途径生成1,3-噁嗪骨架.

关键词: 苯甲酰亚胺高烯丙酯, 全氟碘代烷烃, 胺化全氟烷基化反应, 1,3-噁嗪, 铜催化

Azaheterocycles have been broadly applied in the development of therapeutic agents, agrochemicals and functional material molecules. Azaheterocycles equipped with perfluoroalkyl group usually manifest superior physical and biological properties than their parent molecules, such as showing improved metabolic stability and high lipophilicity. The synthesis of perfluoroalkyl modified azaheterocycles has attracted considerable research interest in recent years. The strategy of intramolecular aminoperfluoroalkylation of alkenes, which functionalize C=C bond with an external perfluoroalkyl group and an internal amine nucleophile in one pot, provides a streamlined synthesis of perfluoroalkyl substituted azaheterocycles. This strategy has been applied by Liu, Sodeoka and other research groups in the synthesis of perfluoroalkyl substituted aziridines, pyrrolidines, lactams and pyrazolines featuring the use of pendent amine, amide, hydrazone or urea group as internal amine source. We have previously developed a copper(I)-catalyzed intramolecular aminotrifluoromethylation reaction of O-homoallyl benzimidates with Togni reagent I for the synthesis of trifluoromethyl containing chiral 1,3-oxazines using a chiral BOX ligand. However, this method is limited to aminotrifluoromethylation reaction as other perfluoroalkyl substituted hypervalent iodine reagents are not easily accessible. Herein, we report our recent research results on the synthesis of perfluoroalkyl substituted 1,3-oxazines using commercial available perfluoroalkyl iodides as perfluoroalkyl source. This intramolecular aminoperfluoroalkylation reaction proceeds selectively in the presence of Cu(OAc)2 catalyst, 1,10-phenanthroline ligand and AgOAc additive. A broad range of O-homoallyl benzimidates and perfluoroalkyl iodides are compatible with the reaction conditions, affording perfluoroalkyl substituted 1,3-oxazines in moderate to good yields. The 1,3-oxazine product can be prepared in gram scale and readily hydrolyzed under mild conditions to give perfluoroalkyl substituted 1,3-amino alcohols. Preliminary mechanism studies revealed that this intramolecular aminoperfluoroalkylation reaction initiated with the addition of a perfluoroalkyl radical to the terminal alkene, and the subsequent functionalization with the benzimidate motif via intramolecular substitution generated 1,3-oxazine products.

Key words: O-homoallyl benzimidates, aminoperfluoroalkylation, perfluoroalkyl iodides, 1,3-oxazines, copper catalysis