On paper, attaching a new substituent to a carbon-carbon double bond is a simple matter of drawing a line between one end of the double bond and whatever you might want to put there. “That’s a really easy disconnection” for synthesis planning, says Tobias Ritter, an organic chemist at the Max Planck Institute for Kohlenforschung.
But it’s not so easy to do in the laboratory.
Every first-year organic chemistry student learns about Friedel-Crafts alkylation, which substitutes a carbon-hydrogen bond with a carbon-carbon bond on an aromatic ring. But there’s no analogous reaction for alkenes, which prefer addition reactions to substitution. Olefin metathesis can swap pieces of alkenes around, but not all pieces are compatible for swapping, and it doesn’t work at all if the double bond is part of a ring.
Now Ritter and his team have devised a protocol for appending alkyl groups to alkenes through cross-coupling with alkyl zinc reagents derived from carboxylic acids (Nature 2026, DOI: 10.1038/s41586-026-10463-1). Their strategy works on virtually any alkene with an available C-H bond, making it the first truly general alkene alkylation method.
“You pick the olefin that you may be interested in, and if you want to diversify it, now you have a relatively straightforward way of doing that,” Ritter says.
Organic synthesis expert Phil Baran of Scripps Research in California calls the work a “genuinely exciting breakthrough” in an email, adding that the alkylation method “unlocks retrosynthetic disconnections we’ve been missing for decades.”
The researchers’ approach is an extension of their previous work using thianthrenium salts to activate alkene C-H bonds. “We had a solution, and then we applied the solution to a problem,” Ritter says.
Ritter and his team used carboxylic acids because they are inexpensive and available in a variety of useful structures. They initially tried converting the acids to redox-active esters to do radical chemistry, but they couldn’t make the alkyl radicals selectively without also creating thianthrenium radicals. So they switched from one-electron to two-electron chemistry.
They figured out that adding zinc would transform the redox-active esters into stable alkyl zinc compounds. From there, it was straightforward to do palladium-catalyzed coupling with the activated alkene.
Ritter says he and this team realized after developing their zinc reagent that researchers in China had reported alkyl zinc compounds made from redox-active esters in 2020, but the approach had been largely overlooked for synthesis. “Sometimes there are some gems that nobody picks up,” he says.
Zachary Wickens, an organic chemist at the University of Wisconsin–Madison who also works with thianthrenium salts for alkene activation, calls the new method “a really powerful approach” that nicely fills a gap in the alkene synthesis tool kit. The coupling is highly stereoselective and it “does things that I think in many cases would be quite difficult” with legacy strategies such as metathesis, he says. It also invites more research into how to make and use thianthrenium and other sulfonium salts in synthesis, he adds. “Every time we get a new cross-coupling reaction that can transform those salts, they become more useful.”
2026 American Chemical Society
