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Biological Chemistry

In Gold (And Palladium) We Trust

An impurity makes gold-mediated couplings both beautiful and complicated

by Carmen Drahl
July 26, 2010 | A version of this story appeared in Volume 88, Issue 30

When it comes to metal catalysis, chemists have learned time and again that every component of a reaction matters, no matter how insignificant it might seem. Sometimes, it’s those trace ingredients that are actually driving the chemistry.

Last month, researchers in Spain added another chapter to that lesson book. They pointed out that certain gold-mediated cross-coupling reactions are significantly affected by tiny amounts of palladium, making it unlikely that gold is the sole catalyst in those couplings (Org. Lett. 2010, 12, 3006). The find comes just a year after other groups discovered the importance of trace amounts of copper in what were thought to be iron-catalyzed cross-couplings (C&EN, July 13, 2009, page 6).

In the past decade, gold has come into its own as a tool in chemistry, catalyzing cycloisomerization reactions, alkyne activations, and more (C&EN, Sept. 24, 2007, page 87). But reports of a gold catalyst mediating carbon-carbon cross-coupling reactions such as the Sonogashira reaction were a bit more surprising, says Antonio M. Echavarren, an organometallic chemist at Spain’s Institute of Chemical Research of Catalonia. “For us it didn’t make much sense to propose a gold-catalyzed cross-coupling reaction,” he says. “We knew Au(I) is very unreactive toward oxidative addition,” which is the first step in a cross-coupling reaction’s catalytic cycle, he adds.

Echavarren and his research team have a long-standing interest in how cross-coupling reactions work. With Pablo Espinet of Spain’s Valladolid University, they took a close look at the process. Palladium, the traditional catalyst for Sonogashira reactions, undergoes oxidative addition with ease. “And it’s known that palladium is a very common contaminant of gold,” Echavarren says. His team suspected that trace amounts of palladium could be behind the surprising gold chemistry.

Sure enough, when the researchers used ultrapure sources of gold, they did not obtain any cross-coupling products. But adding small amounts of palladium improved the yields. They suggest that instead of replacing palladium, gold works together with palladium, playing the role of the copper cocatalyst typically used in Sonogashira chemistry.

Researchers who have proposed gold-catalyzed Sonogashira and Suzuki cross-couplings, including Avelino Corma of Spain’s Polytechnic University of Valencia, did not respond to C&EN’s requests for comment by press time.

“This is really a paper that suggests a possibility,” says Suzanne A. Blum, who studies dual catalysis with gold and palladium at the University of California, Irvine. “There are a number of reasons why one lab may not be able to reproduce another lab’s results,” she cautions. Contamination is one possibility, but there are others, such as incomplete experimental instructions. “We can’t know for sure what happened in this case unless the exact batch of gold that was originally used is tested” for contamination with palladium, she adds. Still, the new result is exciting because it implies that dual gold-palladium catalysis could be applicable more generally than previously thought, she says.

That broader applicability “is a good thing for catalysis” because it opens the door to more tandem reactions, says A. Stephen K. Hashmi, an expert in gold catalysis at the University of Heidelberg, in Germany. Blum, Hashmi, and others have already been turning to the gold-palladium combination to achieve new levels of selectivity (Organometallics 2009, 28, 1275; J. Am. Chem. Soc. 2009, 131, 18022; Angew. Chem. Int. Ed. 2009, 48, 8243).

“I think this is all good news,” says organometallic chemist Amir H. Hoveyda of Boston College. Any stigma that gets attached to this type of discovery is misplaced, he says. “I wouldn’t necessarily view this as a mistake or detraction. I just think that chemists are becoming wiser about the complexity of catalysis,” he says. “It is far more beautiful and complicated than we thought.”


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