• Cis-2-butene (left) and trans-2-butene (right). Notice the positions of the methyl groups (outlined in blue shading) with relation to the double bond.
07/09/2012 07:00:00

New Class of Catalysts Opens Up Green Route to a Range of Chemical Products

Caltech chemists in the lab of Nobel laureate Bob Grubbs have developed a new class of catalysts that will increase the range of chemicals—from pharmaceuticals, insect pheromones, and perfume musks to advanced plastics—that can be synthesized using environmentally friendly methods.

"We have been trying to develop this particular class of catalysts for about 15 years," says Grubbs, the Victor and Elizabeth Atkins Professor of Chemistry at Caltech.

Like the catalysts that earned Grubbs the 2005 Nobel Prize in Chemistry, the new chemicals include the metal ruthenium and help drive a chemical reaction called olefin metathesis. That reaction has proven useful and efficient for making chemical products that involve pairs of carbon atoms connected by double bonds.

"Our original catalysts have found many applications," Grubbs notes, "but one of the deficiencies was the lack of control of the geometry of the double bond."

And, indeed, what sets the new class of catalysts apart is their ability to selectively form products that have a particular geometry.

To understand that geometry, think first of trans fats. Like other fats, trans fats are essentially chains of fatty acids that contain carbon-carbon double bonds. The "trans" refers to the geometry or configuration of groups of atoms with relation to those double bonds—they can be either trans or cis. If the groups of atoms connected to the carbons of the double bond are located kitty-corner to each other, they exist in the trans configuration; if they are on the same side, the bonds are cis double bonds. Natural fats contain cis double bonds. Trans fats are formed during chemical processing, and the unnatural fats have been found to be unhealthy.

In most circumstances, trans double bonds are much more stable than their cis counterparts. Since metathesis is a double-bond forming reaction that tends to form the more stable product, it primarily forms trans double bonds. But there are many compounds that scientists and manufacturers would like to make that include pure cis, rather than trans double bonds. Some desired compounds that contain cis double bonds are pharmaceutical targets; others make it possible to manufacture polymers with enhanced properties.

"People haven't been able to make these cis double bonds using ruthenium-based olefin metathesis before," says Myles Herbert, a graduate student in Grubbs's lab who has been working with the new catalysts. There are alternative methods for making cis double bonds, but the most popular tend to generate a lot of chemical waste, making them less economical and less environmentally friendly than metathesis, which is considered a green chemical reaction.

Herbert has been focusing on one promising application of the new catalysts—using them to synthesize insect pheromones. Insects such as the gypsy moth and the Douglas-fir tussock moth are responsible for massive deforestation around the world, and others destroy acres of crops. Rather than using poisonous pesticides to control such populations, farmers are beginning to attack the problem by spraying their fields with female insect sex pheromones. Male bugs follow pheromones to locate females; raising the concentration of those chemicals effectively overwhelms their senses, so they are unable to find mates.

"These pheromones are all nontoxic, so it would be great if they could be adapted for use on an industrial scale," Herbert says. "Since many of them involve cis double bonds, I'm trying to use the new catalysts and metathesis to find a shorter synthesis that uses cheaper materials to make these pheromones."

A Serendipitous Discovery

The new class of catalysts was discovered largely by chance. Theoretical work by William Goddard III, Caltech's Charles and Mary Ferkel Professor of Chemistry, Materials Science, and Applied Physics, and his group suggested that one particular catalyst might yield products with cis double bonds. So while visiting Grubbs's lab, Koji Endo, from Mitsui Chemicals in Japan, set about trying to synthesize that catalyst, which was later proven to be ineffective. However, in the process of trying to make that catalyst, Endo happened across a very unusual reaction that produced an entirely unexpected compound, which turned out to be the first in this new class of ruthenium catalysts. 

"We had seen complexes that were reminiscent of this before, but they always decomposed," says Grubbs's graduate student Keith Keitz, a coauthor on several papers published in the past year describing the new class of catalysts. "So it was really surprising to us that, first of all, this was stable, and second, that when Koji threw it in with some of our standard reaction conditions, this catalyst showed an unprecedented selectivity for cis double bonds."

The reaction looked promising, but there was room for improvement. The first-generation catalyst yielded a mix of products containing roughly half cis and half trans double bonds (previously, the best catalysts produced mixtures with 10 times as many compounds with trans double bonds). To convince synthetic chemists to begin regularly using metathesis to create compounds containing cis double bonds, the researchers would need a catalyst that generated cis bonds 80–100% of the time. And the catalyst would need to be reusable, without being used up—that is, have a high turnover number. Endo's first catalyst had a turnover number around 50. It also tended to decompose in solution within about two hours of being exposed to air; an ideal catalyst would be stable in solution or even on the bench top for days at a time.

The Grubbs team has now made several versions of the catalyst and found one that can be used at least 1,000 times and is much more stable than the original. "We can expose a solution of this to oxygen, and it will stay alive for more than 12 hours," Keitz says. "If you just take a vial of this powder and leave it on the bench, it will be good for over 10 days."

Going forward, the researchers hope to use the new catalysts to synthesize large chemical rings, or macrocycles. Macrocycles are common in chemical fragrances (particularly musks) and are found in pharmaceuticals used to treat cancer and other diseases. Previous metathesis catalysts have been used to create trans macrocycles for these purposes, but the catalysts could not make rings that had a high cis double bond content. "We're hoping that our new catalysts will make it possible to synthesize these compounds using metathesis—a proven green reaction," says Grubbs.

Over the past year and a half, the Grubbs group has published several papers in the Journal of the American Chemical Society about these new catalysts. The work is financially supported by the National Science Foundation, the National Institutes of Health, Mitsui Chemicals, Inc., the Department of Defense, and the Swiss National Science Foundation.

Written by Kimm Fesenmaier