Chemists set electrons free and break a decades-old chemistry barrier

For decades, however, chemists have faced a basic limitation in how electron transfer works. When two molecules are competing to receive an electron, the electron typically goes to the molecule that is easier to reduce. That natural preference can prevent researchers from directing reactions toward other potentially useful pathways.

Researchers led by chemists at the University of Wisconsin-Madison, working with teams at Colorado State University and the University of Colorado Boulder, have now demonstrated a different approach to reaction design. Their new strategy, recently reported in Nature, addresses a long-standing problem involving electron-transfer selectivity and could make a wide range of previously inaccessible coupling reactions possible.

Releasing Electrons Directly Into Solution

Rather than trying to control which molecule receives an electron through conventional chemical preferences, the researchers developed a catalyst that releases the electron directly into the surrounding solution.

"Our catalyst works a bit differently because it actually just ejects the electron directly into solvent," says Zachary Wickens, a professor in the UW-Madison Department of Chemistry who led the work. "This gives you, more or less, the strongest reductant and the most aggressive source of electrons you could possibly have since a free electron would rather be in basically any molecule than just on its own in solution."

Once released, the free electron is extremely eager to find somewhere else to go. It can attach to the first molecule it encounters, even if that molecule would not normally be the preferred electron recipient based on its ability to stabilize the added electron.

That behavior changes the usual rules governing which reaction pathway wins. As Wickens puts it, "anything is better than the electron freely floating in solution," says Wickens.

Why the Unexpected Selectivity Works

While the Wisconsin team developed and tested the new reaction system in the laboratory, collaborators in Colorado investigated the underlying chemistry to determine why the approach behaves so differently.

Researchers at Colorado State University carried out computational studies, while scientists at the University of Colorado Boulder used spectroscopy to examine the processes controlling the new reaction framework. The Colorado State work was led by Robert Paton with support from the National Science Foundation-funded Center for Sustainable Photoredox Catalysis (SuPRCat).

"Our calculations reveal how the decisive selectivity emerges after electron transfer has already occurred," says Paton. "We found that the desired reactant can escape reversal and continue toward product, while the partner that is easier to reduce is effectively recycled back to its starting material. This explains how the reaction can succeed despite the usual thermodynamic preference."

The findings show that the crucial selection does not necessarily happen when the electron first moves. Instead, the outcome can be determined by what happens afterward. The desired molecule can continue along the pathway that produces the final product, while the molecule that would normally be favored for reduction can return to its original state.

A New Framework for Designing Redox Reactions

The Wickens group has spent the past five years developing the family of catalysts that made this alternative approach to selectivity possible. By changing how chemists think about where and when reaction selectivity is determined, the method could expand the range of molecules that can be connected through electron-transfer chemistry.

According to Wickens, "This is not just another synthetic method; it's a new way to design redox reactions."

The research team included Prof. Zachary Wickens, Joseph M. Edgecomb, Matthew D. Resmini, and Alissia F. Meyer of UW-Madison; Niket Manoj and Prof. Robert S. Paton of CSU; and Prof. Niels H. Damrauer and Arindam Sau of CU Boulder.