化学学报 ›› 2020, Vol. 78 ›› Issue (9): 933-937.DOI: 10.6023/A20060248 上一篇    下一篇

研究论文

N-硫二氟甲基膦酸二乙酯邻苯二甲酰亚胺:一种新的亲电氟烷硫基试剂

沈峰a, 吕龙b, 沈其龙a   

  1. a 中国科学院上海有机化学研究所 有机氟化学重点实验室 分子合成卓越研究中心 中国科学院大学 上海 200032;
    b 中国科学院上海有机化学研究所 上海 200032
  • 投稿日期:2020-06-18 出版日期:2020-09-15 发布日期:2020-07-24
  • 通讯作者: 吕龙, 沈其龙 E-mail:lulong@sioc.ac.cn;shenql@mail.sioc.ac.cn
  • 基金资助:
    项目受国家自然科学基金(Nos.21625206,21632009,21421002)和中国科学院战略性先导科技专项(B类)(No.XDB20000000)资助.

N-[(Diethoxyphosphoryl)difluoromethylthio]phthalimide: A New Electrophilic Fluoroalkylthiolating Reagent

Shen Fenga, Lu Longb, Shen Qilonga   

  1. a Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China;
    b Shanghai Institute of Organic Chemistry, Shanghai 200032, China
  • Received:2020-06-18 Online:2020-09-15 Published:2020-07-24
  • Supported by:
    Project supported by the National Natural Science Foundation of China (Nos. 21625206, 21632009, 21421002) and the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB20000000).

发展了一例新型亲电氟烷硫基试剂:N-硫二氟甲基膦酸二乙酯邻苯二甲酰亚胺,该试剂可以在溴化镁作用下,以温和的条件高效地实现富电子吲哚傅克类型的亲电氟烷硫基化反应,还可在碱促进下与sp3碳亲核试剂,包括β-酮酸酯、氧化吲哚、苯并呋喃酮等,发生亲电氟烷硫基化反应,简单高效地向分子一步引入硫二氟甲基膦酸二乙酯基团.

关键词: 氟, 亲电, 氟烷硫基

A shelf-stable reagent for the preparation of fluoroalkylthiolated compounds, [(diethylphosphonate)difluoro-methylthio]phthalimide 1, was successfully developed, which reacted with a variety of nucleophiles such as electron-rich heteroarenes, β-ketoesters, oxindoles, benzofuranones in high yield, thus providing a new and efficient approach for the introduction of fluoroalkylthiolated phosphonate moiety. General procedure for the preparation of[(diethylphosphonate)difluoromethylthio]phthalimide 1:to a suspension of silver fluoride (7.6 g, 60 mmol) in anhydrous acetonitrile (100 mL) was added diethyl (difluoro(trimethylsilyl)methyl)phosphonate (13.0 g, 50.0 mmol) at -40℃. The mixture was allowed to stir at 0℃ until a dark brown solution was formed (approximately 15 min). N-(Chlorosulfenyl)phalimide (16.0 g, 75.0 mmol) was then added at -40℃, and the resulting mixture was stirred at -40℃ for 2 h. The mixture was filtered, and the solvent was evaporated in vacuo. The residue was recrystallized using the mixed solvent (petroleum ether/dichlor-omethane) three times to give[(diethylphosphonate)difluoromethylthio]phthalimide 1 as a white solid (5.5 g, 30%). General procedure for reaction of indoles with 1:to a 25 mL Schlenk tube charged with indole (35.1 mg, 0.3 mmol) and reagent 1 (132 mg, 0.36 mmol) and magnesium bromide (82 mg, 0.45 mmol) was added 1,2-dichloroethane (2.0 mL). The mixture was stirred at room temperature for 15 min. The mixture was filtered and the solvent was evaporated in vacuo. The residue was purified by flash chromatography on silica gel to give diethyl (((1H-indol-3-yl)thio)difluoromethyl)phosphonate 3a (93 mg, 93%) as a brown oil. General procedure for reaction of soft carbon nucleophile with reagent 1:to a 25 mL Schlenk tube charged with carbon nucleophiles (153 mg, 0.750 mmol), K2CO3 (103 mg, 0.75 mmol) and reagent 1 (182 mg, 0.50 mmol) was added dichloromethane (3.0 mL). The mixture was stirred at room temperature for 12 h. The reaction mixture was filtered and the solvent was evaporated in vacuo. The residue was purified by flash chromatography on silica gel to give ethyl-2-(((diethoxyphosphoryl)difluoromethyl)thio)-1-oxo-2,3-dihydro-1H-indene-2-carboxylate 5b (160 mg, 76%) as a yellow oil.

Key words: fluorine, electrophilic, fluoroalkylthio