This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Restructuring a molecule without rebuilding it from scratch is an increasingly important goal in modern organic chemistry. Skeletal editing is an approach that helps chemists explore new chemical structures and simplify the synthesis of molecules with potential pharmaceutical applications.
But in the case of functional groups such as esters, skeletal editing remains difficult because their carbon–carbon and carbon–oxygen bonds are resistant to cleavage under mild conditions. Now, a research team led by Professor Toshifumi Dohi of Ritsumeikan University, along with Yusuke Yoto, also of Ritsumeikan University, and Dr. Hideyasu China of Doshisha Women's College of Liberal Arts, developed a unique solution inspired by nature.
Their study, published in JACS Au on July 26, 2026, demonstrates that introducing chlorine into hydroxycoumarins can trigger a sequence of bond-cleavage and bond-forming events that removes a carbonyl group and reconstructs the molecule as a coumaranone. "We aimed to develop a new way of editing molecular skeletons for esters, one that could break difficult bonds under mild conditions and immediately reconstruct the molecule into a useful framework," Dohi says. The idea started from the team's interest in a "cut-to-fuse" strategy.
In this concept, halogenation first "cuts" bonds in a cyclic compound, generating a reactive chain, before a subsequent intramolecular reaction "fuses" the chain into a new heterocyclic structure. The researchers projected that a similar process might enable carbonyl deletion—the net removal of a carbonyl unit from hydroxycoumarins. The initial experiments produced an unexpected result.
The team had been investigating fluorine-induced carbon–carbon bond cleavage, but fluorination caused the hydroxycoumarin to fragment into separate products. "Chlorine changed the reaction pathway completely," Dohi says. Treating a hydroxycoumarin with N-chlorosuccinimide (NCS) led to the formation of a chlorinated intermediate that underwent decarbonylative reconstruction, ultimately producing a coumaranone rather than fragmenting the molecule.
The researchers then optimized the reaction and found that the transformation could proceed at room temperature under near-neutral conditions without transition-metal catalysis. Under the optimized conditions, hydroxycoumarin was treated with NCS, water and sodium acetate in ethyl acetate, followed by potassium phosphate. The method produced the model coumaranone in more than 99% yield.
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