Brønsted Acid–Driven C6‐Selective Sulfonylation of Coumarins Promoted by Cu(OTf) <sub>2</sub> : Synthesis of Coumarin–Sulfone Scaffolds

A Cu(OTf) 2 ‐mediated protocol for the regioselective CH sulfonylation of coumarin derivatives with arylsulfonyl chlorides is reported. This transformation exhibits broad substrate scope and excellent functional‐group tolerance, affording a wide range of C6‐sulfonylated coumarins in moderate to excellent yields. The methodology also extends to heteroaromatic frameworks, such as xanthone, and to bioactive scaffolds exemplified by methoxsalane, enabling selective CH sulfonylation even at unconventional positions. Mechanistic investigations, supported by DFT calculations and Fukui function analysis, reveal that transient protonation of coumarin by in situ–generated triflic acid significantly enhances electrophilic susceptibility at the C6 position, thus overriding the intrinsic C3 reactivity of the neutral scaffold. Computational results favor an electrophilic mechanism over a radical process, as no viable single‐electron donor is available to generate a sulfonyl radical under the reaction conditions. The reaction likely proceeds via electrophilic addition of PhSO 2 + to protonated coumarin, followed by a thermodynamically favorable deprotonation step. Overall, this Brønsted acid–assisted sulfonylation provides an efficient, regioselective, and mechanistically well‐supported approach for the functionalization of coumarin and related heteroaromatic systems, thereby expanding the synthetic utility of direct CH sulfonylation reactions.

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Publication Details

Journal
European Journal of Organic Chemistry
Published
2026-03-12
DOI
https://doi.org/10.1002/ejoc.202501148
Primary Topic
Sulfur-Based Synthesis Techniques
Type
article
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article

Brønsted Acid–Driven C6‐Selective Sulfonylation of Coumarins Promoted by Cu(OTf) 2 : Synthesis of Coumarin–Sulfone Scaffolds

Mrinalini Patil, Mukeshkumar Yadav, Pranali Prabhakar Thakur
European Journal of Organic Chemistry
Sulfur-Based Synthesis Techniques
article

Brønsted Acid–Driven C6‐Selective Sulfonylation of Coumarins Promoted by Cu(OTf) 2 : Synthesis of Coumarin–Sulfone Scaffolds

Mrinalini Patil, Mukeshkumar Yadav, Pranali Prabhakar Thakur
article en

Abstract

A Cu(OTf) 2 ‐mediated protocol for the regioselective CH sulfonylation of coumarin derivatives with arylsulfonyl chlorides is reported. This transformation exhibits broad substrate scope and excellent functional‐group tolerance, affording a wide range of C6‐sulfonylated coumarins in moderate to excellent yields. The methodology also extends to heteroaromatic frameworks, such as xanthone, and to bioactive scaffolds exemplified by methoxsalane, enabling selective CH sulfonylation even at unconventional positions. Mechanistic investigations, supported by DFT calculations and Fukui function analysis, reveal that transient protonation of coumarin by in situ–generated triflic acid significantly enhances electrophilic susceptibility at the C6 position, thus overriding the intrinsic C3 reactivity of the neutral scaffold. Computational results favor an electrophilic mechanism over a radical process, as no viable single‐electron donor is available to generate a sulfonyl radical under the reaction conditions. The reaction likely proceeds via electrophilic addition of PhSO 2 + to protonated coumarin, followed by a thermodynamically favorable deprotonation step. Overall, this Brønsted acid–assisted sulfonylation provides an efficient, regioselective, and mechanistically well‐supported approach for the functionalization of coumarin and related heteroaromatic systems, thereby expanding the synthetic utility of direct CH sulfonylation reactions.

European Journal of Organic Chemistry
Center for Excellence in Basic Sciences (IN)
Openalex Percentile: Top 24%
Sulfur-Based Synthesis Techniques
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