Citation: Shen Feng, Lu Long, Shen Qilong. N-[(Diethoxyphosphoryl)difluoromethylthio]phthalimide: A New Electrophilic Fluoroalkylthiolating Reagent[J]. Acta Chimica Sinica, ;2020, 78(9): 933-937. doi: 10.6023/A20060248 shu

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

Shen Feng ^a ,
Lu Long ^b,, ,
Shen Qilong ^a,,

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

Corresponding author: Lu Long, lulong@sioc.ac.cn Shen Qilong, shenql@mail.sioc.ac.cn
Received Date: 18 June 2020
Available Online: 23 July 2020
Fund Project: Project supported by the National Natural Science Foundation of China 21632009the Strategic Priority Research Program of the Chinese Academy of Sciences XDB20000000Project supported by the National Natural Science Foundation of China 21421002Project supported by the National Natural Science Foundation of China 21625206Project 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).

Figures(2)

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.
- fluorine,
- electrophilic,
- fluoroalkylthio
1. [1]
  (a) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320.(b) Landelle, G.; Panossian, A.; Leroux, F. R. Current Top. Med. Chem. 2014, 14, 941.(c) Ni, C.-F.; Hu, M.-Y.; Hu, J.-B. Chem. Rev. 2015, 115, 765.
2. [2]
  (a) Rico, I.; Wakselman, C. Tetrahedron Lett. 1981, 22, 323.(b) Fujita, T.; Iwasa, J.; Hansch, C. J. Am. Chem. Soc. 1964, 66, 5175.(c) Landelle, G.; Panossian, A.; Leroux, F. R. Curr. Topics in Med. Chem. 2014, 14, 941.(d) Xu, X.-H.; Matsuzaki, K.; Shibata, N. Chem. Rev. 2015, 115, 731.
3. [3]
4. [4]
  Selected examples for the development of electrophilic trifluoromethylthiolating reagents:(a) Ferry, A.; Billard, T. Angew. Chem. Int. Ed. 2009, 48, 8551.(b) Baert, F.; Billard, T. Angew. Chem. Int. Ed. 2012, 51, 10382.(c) Alazet, S.; Zimmer, L.; Billard, T. Angew. Chem. Int. Ed. 2013, 52, 10814.(d) Yang, Y.-D.; Azuma, A.; Tokunaga, E.; Yamasaki, M.; Shiro, M.; Shibata, N. J. Am. Chem. Soc. 2013, 135, 8782.(e) Shao, X.-X.; Wang, X.-Q.; Yang, T.; Lu, L.; Shen, Q. Angew. Chem. Int. Ed. 2013, 52, 3457.(f) Xu, C.; Ma, B.; Shen, Q. Angew. Chem. Int. Ed. 2014, 53, 9316.(g) Xu, J.-B.; Chen, P.-H.; Ye, J.-X.; Liu, G.-S. Acta Chim. Sinica. 2015, 73, 1294;(h) Zhang, P.-P; Li, M.; Xue, X.-S.; Xu, C.; Zhao, Q.; Liu, Y.; Wang, H.; Guo, Y.; Lu, L.; Shen, Q. J. Org. Chem. 2016, 81, 7486.(i) Zhang, H.; Leng, X.-B.; Wan, X. L.; Shen, Q. Org. Chem. Front. 2017, 4, 1051.(j) Lu, S.-Y.; Chen, W.-B.; Shen, Q. Chin. Chem. Lett. 2019, 30, 2279.(k) Zhang, H.; Wan, X.-L.; Shen, Q. Chin. J. Chem. 2019, 37, 1041.(l) Yang, X. G.; Zheng, K.; Zhang, C. Org. Lett. 2020, 20, 2026.(m) Shen, F.; Lu, L.; Shen, Q. Chem. Sci. 2020, 11, 8020.
5. [5]
6. [6]
  Ismalaj, E.; Bars, D. L.; Billard, T. Angew. Chem. Int. Ed. 2016, 55, 4790.
7. [7]
  Xiong, H.-Y.; Bayle, A.; Pannecoucke, X.; Besset, T. Angew. Chem. Int. Ed. 2016, 55, 13490.
8. [8]
  Shen, F.; Zhang, P.-P.; Lu, L.; Shen, Q. Org. Lett. 2017, 19, 1032.
9. [9]
  Ivanova, M. V.; Bayle, A.; Besset, T.; Pannecoucke, X.; Poisson, T. Chem. Eur. J. 2016, 22, 10284.
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