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.

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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
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article

Convergent Paired Electrolysis Enables Electrochemical Halogen-Atom Transfer-Mediated Alkyl Radical Cross-Coupling

Ke Zheng, Xiang Sun
7 citations
Journal of the American Chemical Society
Radical Photochemical Reactions
6.55
article

Convergent Paired Electrolysis Enables Electrochemical Halogen-Atom Transfer-Mediated Alkyl Radical Cross-Coupling

Ke Zheng, Xiang Sun
article en
7 citations

Abstract

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.

Journal of the American Chemical SocietyVol. 147(38)
Sichuan University (CN), Green Chemistry (PL)
Openalex Percentile: Top 3%
Radical Photochemical Reactions
6.55
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