A highly efficient metal-free selective 1,4-addition of difluoroenoxysilanes to chromones?

Organic & Biomolecular Chemistry Pub Date: 2022-12-29 DOI: 10.1039/D2OB02152H

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.

Graphical abstract: A highly efficient metal-free selective 1,4-addition of difluoroenoxysilanes to chromones
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