Acta Chimica Sinica ›› 2018, Vol. 76 ›› Issue (12): 951-955.DOI: 10.6023/A18080313 Previous Articles     Next Articles

Special Issue: 有机氟化学



陈栋a, 吉梅山a, 姚英明a, 朱晨a,b   

  1. a. 苏州大学材料与化学化工学部 苏州 215123;
    b. 中国科学院上海有机化学研究所 天然产物有机合成重点实验室 上海 200032
  • 投稿日期:2018-08-02 发布日期:2018-08-27
  • 通讯作者: 姚英明,;朱晨,;
  • 基金资助:


Difunctionalization of Unactivated Alkenes through SCF3 Radical-triggered Distal Functional Group Migration

Chen Donga, Ji Meishana, Yao Yingminga, Zhu Chena,b   

  1. a. College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123;
    b. Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
  • Received:2018-08-02 Published:2018-08-27
  • Contact: 10.6023/A18080313;
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21722205).

Radical-mediated C-SCF3 bond formation via the addition of SCF3 radical to alkenes has become an efficient strategy for the construction of alkyl trifluoromethylthioethers. However, the scope of alkenes is largely limited to activated alkenes in which the presence of adjacent carbonyl or aryl group is required to stabilize the alkyl radical intermediates by p-π conjugation. A few cases involving trifluoromethylthiolation of unactivated olefins have been reported, but in these reactions only a single functional group is incorporated to alkenes. The radical difunctionalization of unactivated olefins remains challenging and has received less attention. Recently, we established a new protocol to realize the radical difunctionalization of alkenes through intramolecularly distal functional group migration. This tactic provides a useful and elegant tool for the elusive functionalization of unactivated olefins. A portfolio of groups such as cyano, heteroaryl, imino, aldehyde, and alkynyl can be readily migrated in the transformation. Herein, we disclose an efficient and practical approach for the trifluoromethylthiolation of unactivated olefins based on the intramolecular migration of heteroaryl and imino groups. The migration is triggered by the addition of SCF3 radical, which is generated from the mixture of AgSCF3 and K2S2O8at room temperature, to alkenes. The reaction demonstrates a high functional group compatibility and broad substrate scope. A variety of nitrogen-containing five- and six-membered heteroaryl as well as imino groups are readily migrated, affording the synthetically valuable alkyl trifluoromethylthioether compounds in good yields. The typical procedure is as follows: a mixture of tertiary alcohol (0.2 mmol), AgSCF3(0.3 mmol), and K2S2O8(0.6 mmol) is loaded in a flame-dried reaction vial which is subjected to evacuation/flushing with nitrogen three times. Dry DMF (2.0 mL) is added to the mixture via syringe, and the mixture is then stirred at room temperature until the starting material is consumed which is determined by TLC. The mixture is extracted with ethyl acetate (10 mL×3). The combined organic extracts are washed with brine, dried over Na2SO4, filtered, concentrated, and purified by flash column chromatography on silica gel (eluent: petroleum ether/ethyl acetate) to give the desired product.

Key words: alkene difunctionalization, trifluoromethylthiolation, migration reaction, radical reaction, heteroaryl