Acta Chimica Sinica ›› 2019, Vol. 77 ›› Issue (9): 911-915.DOI: 10.6023/A19050181 Previous Articles     Next Articles

Special Issue: 有机自由基化学



戴建玲, 雷文龙, 刘强*()   

  1. 兰州大学功能有机分子化学国家重点实验室 化学化工学院 兰州 730000
  • 投稿日期:2019-05-15 发布日期:2019-08-14
  • 通讯作者: 刘强
  • 基金资助:
    项目受国家自然科学基金(Nos. 21572090);项目受国家自然科学基金(21871123);兰州大学中央高校基础研究基金资助(lzujbky-2017-k05)

Visible-Light-Driven Difluoroalkylation of Aromatics Catalyzed by Copper

Dai, Jianling, Lei, Wenlong, Liu, Qiang*()   

  1. State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000
  • Received:2019-05-15 Published:2019-08-14
  • Contact: Liu, Qiang
  • Supported by:
    Project supported by the National Natural Science Foundation of China(Nos. 21572090);Project supported by the National Natural Science Foundation of China(21871123);the Fundamental Research Funds for the Central Universities(lzujbky-2017-k05)

The introduction of difluoromethyl groups into organic molecules not only can dramatically alter physical properties of nonfluorinated counterparts, but also provide valuable CF2-containing building blocks for the synthesis of other difluoromethylenated compounds. Therefore, there is a growing demand to develop efficient and practical methods for the introduction of the difluoromethyl motif. Although significant advances have been made in the preparation of difluoromethylated arenes, these reactions usually required pre-functionalized substrates, precious metal catalysts, elevated temperature, and so on. In the past decade, visible light-driven photoredox catalysis has been proved to be powerful in synthetic radical chemistry. Particularly, direct difluoroalkylations of arenes have been achieved using precious-metal photocatalysts such as ruthenium or iridium polypyridyl complexes. Herein, we are committed to developing a cheap copper-based phororedox system for direct difluoroalkylation of arenes. The key to this approach is the in-situ formation of cuprous photocatalyst from cuprous iodide, an imine ligand (2,9-dichloro-1,10-phenanthroline) and a triaryl phosphine ligand (4,5-bis(diphenylphos- phino)-9,9-dimethyl xanthene). With catalytic amount of reagents mentioned above, the direct difluoroalkylation between arenes and difluoroalkylation reagents (BrCF2CO2Et or BrCF2CONR 1R 2) took place smoothly under 6 W blue LED irradiation at room temperature. A variety of electron-rich arenes, including electron-donating aromatics, indoles, furans, thiophenes, and pyrimidines, could be carbonyldifluoromethylated in moderate to excellent yields. In addition, high yields were obtained for the intramolecular and intermolecular aminocarbonyldifluoromethylation by the catalytic system. Preliminary mechanistic studies reveal that [Cu(dcp)(xantphos)]I (dcp=2,9-dichloro-1,10-phenanthroline, xantphos=4,5-bis(diphenyl phosphino)-9,9-dimethyl xanthene), in situ-formed from CuI, dcp, and xantphos should be the real photocatalyst to catalyze the visible light-driven difluoroalkylation. Difluormethyl radicals, produced by single electron transfer from the excited photocatalyst to difluoroalkylation reagents, should be involved in the difluoroalkylation. In summary, visible-light driven difluoroalkylation of arenes with difluoroalkylation reagents via Cu-catalysis has been developed. The use of the bidentate phosphine ligand and the imine ligand is essential for high efficiency as they could bind to cuprous iodide to generate the photocatalyst in situ. The typical procedure is as follows: a mixture of arenes (0.6 mmol), CuI (0.02 mmol), dcp (0.02 mmol), xantphos (0.02 mmol), K3PO4 (0.4 mmol) and CH2Cl2 (2 mL) were loaded in a flame-dried reaction vial which was subjected to evacuation with argon for 30 min. Subsequently, BrCF2CO2Et (0.2 mmol) was added to the mixture via syringe, and the mixture continued degassing for 5 min. After degassing procedure, the vial was sealed with wax, and irradiated by blue light for 24 h. The reaction was monitored by TLC. Further purification of the evaporated mixture by flash column chromatography on silica gel (eluent: petroleum ether/ethyl acetate) gave the desired product.

Key words: alkyl radical, visible-light photocatalysis, difluoroalkylation, arenes, copper