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

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.

NHC and photoredox catalysis dual-catalyzed 1,4-mono-/di-fluoromethylative acylation of 1,3-enynes

“…Significant progress has been achieved in radical fluoroalkylation, including trifluoromethylation, 4 difluoromethylation, 5–7 and others. However, in terms of radical monofluoromethylation 8–12 of C–C multiple bonds, it still appears to be in its infancy. In this domain, monofluoromethylation of olefins 9,10 is relatively well-documented, and the transformation includes hydro-monofluoromethylation, 9 chloro-monofluoromethylation, 10 a oxy-monofluoromethylation, 10 b – d etc.…”

“…However, in terms of radical monofluoromethylation 8–12 of C–C multiple bonds, it still appears to be in its infancy. In this domain, monofluoromethylation of olefins 9,10 is relatively well-documented, and the transformation includes hydro-monofluoromethylation, 9 chloro-monofluoromethylation, 10 a oxy-monofluoromethylation, 10 b – d etc. Furthermore, driven by cyclization, monofluoromethylative arylation of olefins, 11 alkynes, 12 a and isonitrile 12 b , c has been realized, leading to the direct construction of monofluoromethylated heterocycles.…”