Visible Light-Mediated Monofluoromethylation/Acylation of Olefins by Dual Organo-Catalysis

Jiuli Xia; Yunliang Guo; Zhiguang Lv; Jiaqiong Sun; Guangfan Zheng; Qian Zhang

doi:10.3390/molecules29040790

Visible Light-Mediated Monofluoromethylation/Acylation of Olefins by Dual Organo-Catalysis

Molecules. 2024 Feb 8;29(4):790. doi: 10.3390/molecules29040790.

Authors

Jiuli Xia¹, Yunliang Guo², Zhiguang Lv¹, Jiaqiong Sun², Guangfan Zheng¹, Qian Zhang^{1

3}

Affiliations

¹ Key Laboratory of Functional Organic Molecule Design & Synthesis of Jilin Province, Department of Chemistry, Northeast Normal University, Changchun 130024, China.
² School of Environment, Northeast Normal University, Changchun 130117, China.
³ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.

Abstract

Monofluoromethyl (CH₂F) motifs exhibit unique bioactivities and are considered privileged units in drug discovery. The radical monofluoromethylative difunctionalization of alkenes stands out as an appealing approach to access CH₂F-containing compounds. However, this strategy remains largely underdeveloped, particularly under metal-free conditions. In this study, we report on visible light-mediated three-component monofluoromethylation/acylation of styrene derivatives employing NHC and organic photocatalyst dual catalysis. A diverse array of α-aryl-β-monofluoromethyl ketones was successfully synthesized with excellent functional group tolerance and selectivity. The mild and metal-free CH₂F radical generation strategy from NaSO₂CFH₂ holds potential for further applications in fluoroalkyl radical chemistry.

Keywords: NHCs; alkenes; metal-free; monofluoromethylation/acylation; organic photocatalyst.

Grants and funding

We thank the NSFC (22193012, 22001157, 21831002, and 22201033), Natural Science Foundation of Jilin Province (20230101047JC, YDZJ202201ZYTS338), Jilin Educational Committee (JJKH20231295KJ, JJKH20231302KJ), and the Fundamental Research Funds for the Central Universities (2412022ZD012, 2412022QD016, 2412021QD007) for their generous financial support.