Convergent Paired Electrolysis Enables Electrochemical Halogen-Atom Transfer-Mediated Alkyl Radical Cross-Coupling
The direct cross-coupling of unactivated alkyl halides with aryl or heteroaryl partners remains a fundamental challenge in synthetic chemistry due to their inertness and propensity for side reactions. Herein, we report a transition-metal-free electrochemical halogen-atom transfer strategy that enables efficient alkyl radical cross-coupling via convergent paired electrolysis. In this system, anodically generated α-aminoalkyl radicals mediate the activation of alkyl iodides, while aryl/heteroaryl aldehydes or nitriles undergo cathodic reduction to afford persistent ketyl radical anions or aryl radical anions. The matched redox processes facilitate selective radical-radical anion cross-coupling to furnish diverse alcohols and C(sp<sup>3</sup>)-C(sp<sup>2</sup>) coupling products under mild conditions. This operationally simple, scalable protocol exhibits broad functional group tolerance and is applicable to a wide range of primary, secondary, and tertiary alkyl iodides and structurally diverse aryl and heteroaryl coupling partners. The utility of this strategy is further demonstrated in the late-stage modification of natural products, biomolecules, and pharmaceuticals.
Authors
- Ke Zheng (ORCID: https://orcid.org/0000-0002-3345-7715)
- Xiang Sun (ORCID: https://orcid.org/0009-0009-5018-872X)
Institutions
- Sichuan University (CN)
- Green Chemistry (PL)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2025-09-09
- DOI
- https://doi.org/10.1021/jacs.5c10472
- Citations
- 7
- Primary Topic
- Radical Photochemical Reactions
- Type
- article
- Field-Weighted Citation Impact
- 6.55