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

Abstract

The mono/difluoromethyl (CFH₂/CF₂H) group could act as a metabolically stable bioisostere of lipophilic hydrogen bond donors, playing a vital role in drug discovery. The direct introduction of the fluoromethyl group into organic molecules represents a challenging and attractive task in organic chemistry. Herein, we describe visible light-mediated NHC and photoredox co-catalyzed three-component 1,4-mono-/di-fluoromethylative acylation of 1,3-enynes by employing bench-stable and cost-effective sodium fluoromethyl sulfite and easily accessible benzoyl fluoride. SO₂ might undergo reversible coupling with the propargyl radical or allene radical, thus playing a critical role in unprecedented radical monofluoromethylation of 1,3-enynes. This approach provides a modulized platform for the synthesis of fluoromethyl-containing allene ketones.