A highly efficient metal-free selective 1, 4-addition of difluoroenoxysilanes to chromones. Issue 5 (10th January 2023)

• Record Type: Journal Article
• Authors: Wang, Xi-Yu; Yang, Min; Zhou, Ying; Zhou, Jian; Hao, Yong-Jia
• Is Part Of: Organic & biomolecular chemistry. Volume 21:Issue 5(2023)
• Page Start: 1033
• Page End: 1037
• Publication Date: 2023-01-10
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d2ob02152h
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : An efficient HOTf-catalyzed 1, 4-addition reaction of difluoroenoxysilanes to chromones was developed, providing rapid access to valuable C2-difluoroalkylated chroman-4-ones. 3g showed antiproliferative effect on HCT116 cells with an IC50 of 6.37 μM. Abstract : A highly efficient metal-free selective 1, 4-addition reaction of difluoroenoxysilanes to chromones was developed using the low-cost and readily available HOTf as the catalyst, which is a facile and straightforward method to access valuable C2-difluoroalkylated chroman-4-one derivatives. Interestingly, the products could be readily converted to the difluorinated bioisostere of the natural product ( S )-2, 6-dimethylchroman-4-one and a difluorinated benzo-seven-membered heterocycle via the Schmidt rearrangement reaction. In addition, the in vitro anti-proliferative activities of these synthesized derivatives against human colon carcinoma cells (HCT116) revealed that compound 3g exhibited potent inhibitory effect on HCT116 cancer cells with an IC50 value of 6.37 μM, representing a novel lead compound for further structural optimization and biological evaluation.