Electron transfer is a powerful way to accomplish chemical transformations, especially when driven by light or electricity.
Redox reactions naturally depend on how easy or difficult it is for the molecules involved to accept or part with electrons, a property described by their reduction or oxidation potential. The molecule that is easiest to give an electron to will get it first, a property that chemists can leverage to design highly selective reactions. But a reaction that depends on selectively giving an electron to the more reluctant of two possible acceptors will be prohibitively difficult.
Chemists have now come up with a strategy to do selective light-driven redox chemistry that doesn’t depend on reduction potentials (Nature 2026, DOI: 10.1038/s41586-026-10897-7). Their approach makes it possible to couple molecules that have mismatched potentials.
“It’s a different kind of blueprint for designing selective redox reactions,” says Zachary Wickens of the University of Wisconsin–Madison, who led the method-development side of the project.
The researchers’ solution involves giving out electrons indiscriminately using an electrochemically generated photocatalyst. As quickly as it spits out the electrons into solution, the catalyst can also quickly take them back if they aren’t immediately funneled into a productive reaction. The upshot is that the reaction selectivity becomes dependent on the reversibility of the electron-transfer step rather than its difficulty.
“You’re sort of playing different rates against each other in very clever ways,” says coauthor Niels Damrauer of the University of Colorado Boulder, whose group carried out time-resolved spectroscopy experiments to investigate the reaction mechanism.
The researchers developed and validated their strategy using a [3+2] cycloaddition reaction between a cyclopropyl ketone and an alkene. Though the alkene is the more ready electron acceptor, it can pass its extra electron right back to the photocatalyst. Meanwhile, giving an electron to the ketone triggers an irreversible ring opening. The ring-opened radical anion then reacts with the alkene to make the cycloaddition product.
By combining protective back electron transfer and an irreversible step, “they’re able to kind of unearth an entirely new selectivity control feature,” says Joshua Barham of the University of Strathclyde, who works on photoelectrochemistry for organic synthesis but was not involved in the work. The new strategy also offers the ability to do highly reducing chemistry with more control than other approaches, he adds.
The ketone still technically accepts electrons a little slower than the alkene, but that is OK, Wickens says. “All you need is to get some shots on goal,” and the irreversible reaction takes care of the rest, he says.
“It’s a really simple principle, but it’s very powerful, with a lot of potential applications,” says Phillip Milner of Cornell University, who also researches strategies for driving challenging electron-transfer reactions. He adds that the work is a great reminder of why it’s important to understand reaction mechanisms, and of the power of cross-disciplinary collaborations to deepen that understanding.
Although the method won’t work if one of the starting materials doesn’t undergo an irreversible reaction, Barham says the researchers’ approach opens up lots of fascinating possibilities such as late-stage modifications of complex molecules or remediating environmental pollutants. “I’m quite excited about it. It’ll be interesting to see where it goes.”
Wickens and Damrauer both say they plan to keep exploring ways to leverage this selectivity strategy, and they welcome other researchers to do the same. “When you sort of push the boundaries of reducing power or oxidative power, what kinds of things will emerge in terms of selectivity and control that weren’t known before?” Damrauer asks.
