Heterogeneous Copper Single‐Atom Catalyzed Three‐Component Radical Difunctionalization of Alkenes
1
@NC) featuring atomically dispersed Cu–N
4
sites that enable efficient three‐component coupling of alkenes, quinoxalinones, and polyhalogenated alkanes. This catalytic system simultaneously installs both gem‐dihaloalkyl and quinoxalinone pharmacophores across a broad substrate scope (52 examples), including traditionally challenging unactivated aliphatic alkenes. Remarkably, Cu
1
@NC maintains excellent catalytic stability over >10 cycles with >95% of its initial activity retained and demonstrates robust scalability (72%–77% isolated yields in gram‐scale reactions). Most significantly, this catalytic system enables efficient late‐stage difunctionalization of alkenes derived from complex bioactive molecules (e.g., ibuprofen, borneol derivatives), underscoring its potential for pharmaceutical applications. Mechanistic investigations reveal that Cu
1
@NC mediates the radical pathway through two essential single‐electron transfer processes: activating TBHP to generate oxygen‐centered radicals and oxidizing intermediate IM‐4 to regenerate the catalytic center. This study delivers an atom‐ and step‐economical route to valuable drug‐like scaffolds, thus opening new avenues for heterogeneous catalysis in multicomponent reactions.
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Jakub S. Cyniak, Daria Szelag · 2026
- Published
- Dec 02, 2025
- Vol/Issue
- 368(2)
- License
- View
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