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Convergent Paired Electrolysis Enables Electrochemical Halogen-Atom Transfer-Mediated Alkyl Radical Cross-Coupling
1Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
Journal of the American Chemical Society
|September 9, 2025
Summary
This study introduces a metal-free electrochemical method for cross-coupling unactivated alkyl halides. The strategy uses halogen-atom transfer and paired electrolysis to efficiently form C(sp3)-C(sp2) bonds under mild conditions.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Electrochemistry
Background:
- Direct cross-coupling of unactivated alkyl halides with aryl/heteroaryl partners is challenging.
- Inertness and side reactions limit traditional synthetic methods.
Purpose of the Study:
- To develop a transition-metal-free electrochemical strategy for alkyl radical cross-coupling.
- To enable efficient formation of C(sp3)-C(sp2) bonds under mild conditions.
Main Methods:
- Utilized a halogen-atom transfer (HAT) strategy via convergent paired electrolysis.
- Anodic generation of α-aminoalkyl radicals to activate alkyl iodides.
- Cathodic reduction of aryl/heteroaryl aldehydes or nitriles to radical anions.
Main Results:
- Achieved selective radical-radical anion cross-coupling.
- Synthesized diverse alcohols and C(sp3)-C(sp2) coupled products.
- Demonstrated broad functional group tolerance with various alkyl iodides and aryl/heteroaryl partners.
Conclusions:
- The developed electrochemical protocol is operationally simple, scalable, and metal-free.
- Applicable to late-stage modification of complex molecules including natural products, biomolecules, and pharmaceuticals.
- Offers a versatile approach for constructing C(sp3)-C(sp2) bonds.
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