摘要/Abstract

以CuI为铜源, 通过原位形成光催化剂的途径, 实现了室温下可见光驱使铜催化溴二氟乙酸乙酯、溴二氟酰胺等对芳烃及杂芳烃的二氟烷基化反应. 该反应条件温和、原料廉价易得、底物适用范围广、产率较高, 为合成二氟烷基(杂)芳烃化合物提供了一种方法. 机理研究表明, 该反应可能经历了单电子转移的自由基反应历程.
关键词: 烷基自由基, 可见光催化, 二氟烷基化反应, 芳烃, 铜
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


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