Silicon insertion methods join skeletal-editing toolbox

Skeletal-editing reactions are offering chemists an ever-expanding toolbox of techniques to add, swap, or subtract atoms in molecular backbones. Now two research teams have developed complementary approaches to insert silicon atoms into ring structures using simple reagents, potentially opening up routes to silicon-containing drug analogs and polymers.

“Frankly speaking, methodologies for skeletal editing involving silicon insertion are quite niche,” Hao Wei of Northwest University in China, who co-led one of the teams, says in an email. Until now, he adds, “relevant examples are genuinely scarce.”

Incorporating silicon into drug scaffolds could help to fine-tune their medicinal properties. The carbon-silicon bond is longer than carbon-carbon, for example, which could subtly reshape potential drug molecules and alter how they interact with biological receptors.

But this approach has been held back by a dearth of suitable reactions for preparing organosilicon compounds. Some previous silicon insertion methods have depended on impractically complex or fragile silicon reagents.

Wei’s approach is instead based on using readily available dialkylsilanes. In the presence of a nickel catalyst, these molecules can insert into the carbon-oxygen bond in benzofurans, expanding the ring to form a six-membered oxasilacycle (J. Am. Chem. Soc. 2026, DOI: 10.1021/jacs.6c00274). The reaction is also economical with its atoms, ejecting only hydrogen molecules from the dialkylsilane. “That’s a really big benefit of their reaction,” says Michinori Suginome at Kyoto University, who developed the second silicon-based editing method with his graduate student Yunhao Song.

Wei’s team showed that their oxasilacycles could be used to make more-complex ring systems or as a stepping stone to swap silicon for other functional groups, including a carbonyl, an alkene, or a hydroxyboron.

One drawback is that the reaction doesn’t work with arylsilanes. That’s where Suginome’s method could come in handy. It uses silicon reagents that can carry a wide range of alkyl and aryl groups—as long as they have a phenyl group and a hydrogen atom that can pair up and depart during the reaction (ACS Cent. Sci. 2026, DOI: 10.1021/acscentsci.6c00159).

With the help of an iridium catalyst, the silicon reagent loses its phenyl group and hydrogen and then inserts into the carbon-oxygen bond of furans, benzofurans, and similar compounds. The versatile reaction tolerates a wide variety of functional groups.

“It has the merit of creating a complicated structure very easily,” Suginome says. In one example, Suginome’s team used the method to make a complex polycyclic silicon spirocycle from simple starting materials in just two steps. He and Song also used the method to drive a polymerization process using a silane monomer that was tethered to a benzofuran group, so that the molecules could couple head to tail.

The team’s reaction even worked when germanium was used in place of silicon, which enabled them to insert a diphenylgermylene unit into benzofuran. This version of the reaction could help to open up unexplored areas of organogermanium chemistry, Suginome says.