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 CH 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 CH 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 CH sulfonylation reactions.
Authors
- Mrinalini Patil
- Mukeshkumar Yadav
- Pranali Prabhakar Thakur
Institutions
- Center for Excellence in Basic Sciences (IN)
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
- Field-Weighted Citation Impact
- 0.00