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Chemists fracture rings to install fluorine

Reaction opens unstrained nitrogen rings furnishing alkyl fluorine compounds

by Tien Nguyen
July 14, 2018 | A version of this story appeared in Volume 96, Issue 29

Reacting a fluorinating reagent with a six-membered nitrogen-containing ring in the presence of silver tetrafluoroborate opens the ring, fluorinates one of the carbons and oxidizes another.

To construct new bonds, as chemists are wont to do, they must first break bonds. But some bonds give way easier than others. Researchers can readily split carbon-carbon double bonds for further functionalization, yet they struggle to crack relatively inert, C–C single bonds. A new method developed by Richmond Sarpong and coworkers at the University of California, Berkeley, now cleaves C–C bonds in nitrogen-containing rings (Science 2018, DOI: 10.1126/science.aat6365). Using an excess of a silver salt and a common fluorinating reagent, the reaction (example shown) unfurls the ring to a linear alkyl chain with a fluorine atom at one end, a functional group coveted by chemists for its ability to modulate a molecule’s properties. In some cases, the method also introduces a formyl group on the nitrogen at the other end. The team proposes that the reaction proceeds through oxidation followed by radical ring opening. They successfully opened four-membered rings and larger ones, but five-membered rings were mostly just oxygenated. The researchers also demonstrated the ring-opening fluorination of two peptides, a strategy that could be immediately applicable in drug discovery or biological uses, Sarpong says. In addition, the team showed the geminal difluorination of rings using 0.25 equivalents of a silver salt and hope to lower the amount of metal needed in future reactions.


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