A Radically New Approach to Synthetic Chemistry – Zoo House News
Scientists at the US Department of Energy’s (DOE) Brookhaven National Laboratory helped measure how unpaired electrons in atoms on one end of a molecule can drive chemical reactivity on the opposite side of the molecule. As detailed in a recent article published in the Journal of the American Chemical Society, this work in collaboration with Princeton University shows how molecules containing these so-called free radicals could be used in a whole new class of reactions.
“Most reactions involving free radicals occur at the site of the unpaired electron,” explained Brookhaven Lab chemist Matthew Bird, one of the paper’s co-corresponding authors. The Princeton team had become experts in using free radicals for a range of synthetic applications, such as polymer upcycling. But they wondered if free radicals could also affect reactivity at other parts of the molecule by pulling electrons away from those more distant locations.
“Our measurements show that these radicals can exert powerful ‘electron-withdrawing’ effects that make other parts of the molecule more reactive,” Bird said.
The Princeton team demonstrated how this long-distance train can overcome energy barriers and bring otherwise unreactive molecules together, potentially leading to a new approach to synthesizing organic molecules.
The research drew on the combined resources of a Princeton-led DOE Energy Frontier Research Center (EFRC) focused on Bio-Inspired Light Escalated Chemistry (BioLEC). The collaboration brings together leading synthetic chemists with groups that have advanced spectroscopic techniques to study reactions. Funding was recently extended for another four years.
Robert Knowles, who led Princeton’s role in this research, said: “This project is an example of how BioLEC’s combined expertise allowed the team to quantify an important physical property of this radical species, which in turn allowed us to to develop the resulting synthesis methodology. “
The Brookhaven team’s main contribution is a technique called pulse radiolysis, which is only available at Brookhaven and one other US location
“We use the Laser Electron Accelerator Facility (LEAF) – part of the Accelerator Center for Energy Research (ACER) in Brookhaven’s Chemistry Division – to generate intense, high-energy electron pulses,” Bird explained. “These pulses allow us to add or subtract electrons from molecules to produce reactive species that are difficult to produce with other techniques, including short-lived reaction intermediates. With this technique, we can step into part of a reaction and monitor what’s happening.”
For the current study, the team used pulse radiolysis to create molecules with oxygen-centered radicals, and then measured the “electron-withdrawing” effects on the other side of the molecule. They measured electron attraction by tracking how strongly the oxygen on the opposite side attracts protons, positively charged ions sloshing around in solution. The stronger the radical’s attraction, the more acidic the solution needs to be for protons to bind to the molecule, Bird explained.
The Brookhaven scientists found that the acidity had to be high to allow proton capture, meaning the oxygen radical was a very strong electron withdrawing group. That was good news for the Princeton team. They then showed that it is possible to exploit the “electron-withdrawing” effect of oxygen radicals by making parts of molecules that are generally inert more chemically reactive.
“The oxygen radical induces a transient ‘polarity reversal’ within the molecule – causing electrons that would normally want to stay on that far side to move to the radical to make the ‘far’ side more reactive,” Bird explained.
These results enabled a novel substitution reaction on phenolic-based starting materials to produce more complex phenolic products.
“This is a great example of how our pulse radiolysis technique can be applied to cutting-edge scientific problems,” said Bird. “We were very pleased to welcome Nick Shin, an excellent PhD student from the Knowles group, for this collaboration. We look forward to further joint projects in this second phase of BioLEC and to what new problems we can investigate with pulse radiolysis. “
Brookhaven Lab’s role in this work and the EFRC at Princeton were funded by the DOE Office of Science (BES). Princeton received additional funding for the synthesis work from the National Institutes of Health.