Carbon-atom transfer with spiro style

A new reagent has moved carbon-atom transfer out of the chemical flatlands, allowing chemists to place a single carbon atom so that it makes bonds to four different substituents. The reagent makes molecules with spiro centers, which could be unusual motifs in drug candidates or could form the cores of highly strained molecules.

Chemists led by Max M. Hansmann of the Technical University of Dortmund were inspired by earlier work they’d done on a carbon-transfer agent that combined diazo chemistry and phosphorus ylide chemistry. But the molecules they made with that reagent were all linear around the added carbon—they were alkynes and allenes.

To transfer tetrahedral carbons, the researchers decided to change their phosphorus ylide to a sulfur ylide, generating the diazosulfur ylide reagent Ph₂S=C=N₂ (where Ph is phenyl). “The reactivity of a sulfur ylide is very different compared to the reactivity of a phosphorus ylide. This is well known in classical organic synthesis,” Hansmann says.

In one example (shown), the chemists use the reagent to create an unusual bridged spiropentane. The new reagent’s diazo portion first reacts with an olefin via a [3+2] cycloaddition. This is followed by cyclopropanation on another olefin with the sulfur ylide portion of the reagent. Warming the reaction eliminates N₂, leaving behind the bridged spiropentane (Science 2025, DOI: 10.1126/science.ads5974).

Because the diazosulfur ylide is air sensitive and can decompose violently if heated, Hansmann’s team developed a user-friendly, one-pot approach that lets chemists generate and use the reagent without the need to isolate it. “Ideally, you just want to make it in situ, keep it in solution, and trap it,” Hansmann says.

Richmond Sarpong, a synthetic organic chemist at the University of California, Berkeley, who was not involved in the work, says that the new reagent gives chemists another creative way to add a single carbon to olefins. “It allows access to a range of interesting spiro-fused compounds that will otherwise be difficult to prepare,” he says in an email. “I look forward to seeing other applications of this reagent in synthesis.”