Selectivity Achieved Despite Indiscriminate Photoreduction in New Study

Superselective bond formation in organic synthesis is often ruled by single-electron transfer (SET) chemistry: the substrate with the more favorable redox potential typically reduces faster, dictating the outcome. But that redox “gatekeeping” becomes a major limitation when the desired transformation requires productive SET of a harder-to-reduce partner. In many systems, this thermodynamic mismatch prevents productive coupling altogether, stalling designs that would otherwise enable new carbon–carbon or carbon–heteroatom connectivity.

Now, researchers report a different selectivity logic that largely ignores redox potentials. In a study published in Nature (2026), the team introduces a selectivity paradigm for outer-sphere SET in which reaction rates become dominated by diffusion-limited electron transfer rather than by the relative thermodynamics of the substrates.

The key enabling tool is a class of “super-potent” photoreductants. Under irradiation, these reagents deliver electrons so aggressively that the SET step proceeds at the fastest pace allowed by molecular encounter rates. As a result, the usual expectation—more easily reduced substrates win the competition—no longer holds.

Instead, the fate of the electrons is determined downstream. After SET generates radical intermediates, subsequent chemical steps compete against back electron transfer (BET), which can rapidly quench radicals. Selectivity therefore emerges from the relative kinetics of productive radical chemistry versus BET, creating an outcome profile that can differ radically from classical redox control.

To validate the concept, the group studied radical annulation reactions between cyclopropyl ketones and alkenes that are much easier to reduce. Historically, pairing such mismatched partners is problematic because ketone reduction is thermodynamically disfavored.

Despite this, the photoreduction strategy promotes selective radical annulation even when the ketone reduction step becomes less favorable by as much as a volt. The approach effectively “decouples” the selectivity from the redox potential mismatch that would normally block the transformation.

More broadly, the findings provide a blueprint for designing SET reactions that intentionally violate conventional redox potential rules. By using sufficiently powerful photoreductants to reach diffusion-limited SET, chemists can shift control from electron-transfer thermodynamics to radical survival and reactivity.