Acta Chimica Sinica ›› 2019, Vol. 77 ›› Issue (9): 884-888.DOI: 10.6023/A19060220 Previous Articles     Next Articles

Special Issue: 有机自由基化学 纪念南开大学化学学科创建100周年



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
  • 投稿日期:2019-06-18 发布日期:2019-08-13
  • 通讯作者: 陈弓,何刚;
  • 基金资助:

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 Published:2019-08-13
  • Contact: Chen, Gong,He, Gang;
  • 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)

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