Photoredox/Copper Dual-Catalyzed Formal α-Nucleophilic Addition to α,β-Unsaturated Enones for the Synthesis of Chiral γ-Lactones

Abstract

The inherent polarity mismatch suggests that direct α-nucleophilic addition is disfavored both thermodynamically and kinetically under conventional conditions. However, indirect α-nucleophilic addition reactions of α,β-unsaturated carbonyl compounds via copper-catalyzed radical pathways have been well established. Herein, we reported a formal asymmetric α-nucleophilic addition reaction of α,β-unsaturated carbonyl compounds through merging photoredox catalysis with copper catalysis. This transformation proceeds via radical addition to an α,β-unsaturated carbonyl compound, followed by a C–O bond cross-coupling reaction to afford the corresponding chiral γ-lactones. With this strategy, a diverse range of chiral γ-lactones bearing a quaternary stereocenter could be afforded.

Keywords

Radicals / Chiral γ-lactones / Photocatalysis / Copper catalysis / α-Nucleophilic addition / α,β-Unsaturated enones / C–C formation / C–O formation

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