Lehigh University
Lehigh University


A Radical Approach to Greener Chemistry

A slow electron waltz: Catalysis in single electron steps with radicals as intermediates is essential for an atom-economical arylation of epoxides with a proton-coupled electron transfer as a key step.

An international team of chemists from Lehigh University and Germany have developed a new method for jump-starting common industrial chemical reactions with a single-electron catalyst that regenerates itself during the reaction.

Described as “a slow electron waltz” in the German journal Angewandte Chemie, the potentially novel approach to catalytic reactions employs oxidative additions and reductive eliminations in single electron steps. The process passes a single electron borrowed from titanium (III) through a complex chemical dance that turns substituted benzenes containing pendant epoxides into indoles that are precursors to numerous pharmaceutically important compounds.

The new method avoids the waste of using a “sacrificial” additional metal to cause the reaction, like manganese or zinc, toxic metals that are commonly consumed in reactions employed in the fine chemical, polymer and pharmaceutical industries.  Instead, it employs less than one percent of the titanium catalyst per each mole of primary reactants. Traditional industrial reactions of this type can require just as much catalyst as they do raw feeder materials, making the reactions inefficient and expensive.

“We like to think of this research as a step towards a greener version of free-radical chemistry, said Robert Flowers, chair of Lehigh’s department of chemistry and an author of the paper Catalytic, Atom-Economical Radical Arylation of Epoxides. “Even if you can increase the efficiency of a large-scale industrial reaction by one percent it could save millions of dollars. Plus, any process where you are creating less waste is very important and that is the ultimate goal.”

Industrial-scale chemistry is all about synthesizing complex compounds from molecularly simply, raw materials. The fewer steps to turn “feed stocks,” derived from petroleum, into complex products or fine chemicals, the more efficient, cheaper and green the industry can be.

Flowers and his colleagues exploited the innate capability of titanocene, in which titanium undergoes reversible electron-transfer reactions. “Once we generate the intermediate free radical, it reduces the titanium and regenerates it,” said Flowers. “So you get electron transfer to the substrate, an intra-molecular reaction and then electron transfer back to the metal.”

The research team used infrared spectroscopy to observe the reduction of titanium (IV) to (III), watched the catalyst levels decrease as the starting material converted to a final product, then monitored the titanium catalyst rise back to its initial concentration. Placing more starting material into the reaction—and no further catalyst—continued the reaction.

The development of efficient catalytic reactions is one of the central goals of synthetic chemistry and arguably the most important for the invention of novel, sustainable processes.  Radical based transformations are among the most attractive methods for use in catalytic cycles. Flowers’ research team and collaborations revolve around developing new synthetic reactions and exploring the molecular mechanisms behind them.  They are currently examining intermolecular reactions and additions initiated through single electron reduction of other functional groups including ketones, aldehydes, and esters.

The research was funded by the National Science Foundation and the Deutsche Forschungsgemeinschaft. The study was conducted by Professor Andreas Gansäuer, Maike Behlendorf, Daniel von Laufenberg, André Fleckhaus and Christian Kube of the Universität Bonn; and Flowers and Dhandapani V. Sadasivam of the Department of Chemistry at Lehigh University.

The full article, online in advance of publication, is available at http://onlinelibrary.wiley.com/doi/10.1002/anie.201200431/suppinfo

Story by Jordan Reese

Posted on Thursday, April 26, 2012

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