Copper-mediated cascade radical cyclization of olefins with naphthalenyl iododifluoromethyl ketones

• Published in: Organic & biomolecular chemistry Vol. 17; no. 26; pp. 6426 - 6431
• Main Authors: Peng, Peng, Huang, Guo-zhi, Sun, Ying-xin, Wang, Xing, Wu, Jing-jing, Wu, Fan-hong
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 14.07.2019; Royal Society of Chemistry
• Subjects: Alkenes; Chemistry; Chemistry, Organic; Copper; Crystallography; Density functional theory; Drug discovery; Intermediates; Ketones; Physical Sciences; Powder; Regioselectivity; Science & Technology; Stereoselectivity; CATALYZED DIRECT DIFLUOROMETHYLATION; CONVENIENT SYNTHESIS; ALKENES; INTRAMOLECULAR CYCLIZATION; ACIDS; TANDEM CYCLIZATION; INHIBITORS; DIFLUOROALKYLATION; GAMMA-BUTYROLACTONES; ACCESS
• ISSN: 1477-0520; 1477-0539; 1477-0539
• DOI: 10.1039/c9ob00916g

Copper-mediated radical cyclization of naphthalenyl iododifluoromethyl ketones with olefins was successfully developed to generate a series of unprecedented gem -difluorodihydrophenanthrenones, especially 2,2-difluoro-3,4-dihydrophenanthren-1(2 H )-one derivatives. This strategy features the use of cheap copper powder and excellent regioselectivity and diastereoselectivity, thus providing a facile approach for application in drug discovery and development. Preliminary mechanistic studies indicate the involvement of difluorinated radical intermediates. Density functional theory (DFT) calculation was performed to provide further evidence for regioselectivity. Copper-mediated radical cyclization of naphthalenyl iododifluoromethyl ketones with olefins was developed to generate a series of unprecedented gem -difluorodihydrophenanthrenones with excellent regioselectivity.