Helping Reactions ‘Dance’

The story07_ of the Nobel Prize-winning breakthrough in metathesis

Some scientific breakthroughs are “discoveries” in the common sense of the word — such as Alexander Fleming’s startling 1928 discovery of penicillin growing in a petri dish. But breakthroughs that are potentially just as significant can also occur when creative minds makes new connections between other scientists’ findings.

Organic chemist Robert Grubbs, co-winner of the Nobel Prize in Chemistry, is an excellent example of the latter kind of breakthrough. Grubbs, the Victor and Elizabeth Atkins Professor of Chemistry at the California Institute of Technology, was supported by a grant from the ACS Petroleum Research Fund as he developed a new catalyst for the metathesis method in organic synthesis — one that offers a wide variety of applications that are already benefiting people, society and the environment.

Metathesis literally means ‘change places,’ and the reaction has been compared to couples changing partners in a dance.

A curious reaction

As a post-doc in the late-1960s, Grubbs learned about an interesting reaction called metathesis that had been recently discovered by accident. The literal meaning of the word is ‘change places,’ and the reaction has been compared to couples changing partners in a dance.

In metathesis reactions, double bonds among carbon atoms are broken and reformed in ways that cause atom groups to change places. In this unique type of organic reaction, certain atoms can be selectively stripped out from a compound and replaced with atoms that were previously part of another compound. The result is a custom-built molecule with specialized properties — and an innovation that can lead to better drugs for the treatment of disease, or better electrical conducting properties for specialized plastics, for example.

“Back in the ‘60s, no one had any idea how metathesis happened,” Grubbs recalled in an interview, “and that’s what attracted me to it.” A few years later, in 1971, French chemist Yves Chauvin was the first to explain in detail how the reaction functioned, and identified certain types of metal compounds that could act as catalysts, although they were not efficient enough to have any clear practical application. Almost two decades later, in 1990, inorganic chemist Richard Schrock became the first to produce an efficient metal-compound catalyst for metathesis.

Finding better catalysts

Working along a parallel line of inquiry in olefin metathesis, Grubbs was developing catalysts with ruthenium as the active metal. In 1992, he demonstrated that these new catalyst molecules had advantages over earlier ones, including the fact that they were stable in air, could be used in the presence of alcohols, water and carboxylic acids, and showed greater selectivity, although lower reactivity, than Schrock’s catalysts.

In 2005 Grubbs, Chauvin, and Schrock were selected as joint winners of the Nobel Prize in Chemistry “for the development of the metathesis method in organic synthesis.”

Fast-forward to 2008, and the industrial use of Grubbs’ catalysts has spread throughout the world. In fact, metathesis is used daily in the chemical industry, mainly in the development of pharmaceuticals and of advanced plastic materials. Thanks to Grubbs’ and his co-Laureates’ contributions, synthesis methods have been developed that are:

• more efficient (requiring fewer reaction steps and resources and generating less waste)
• simpler (stable in air, at normal temperatures and pressures)
• “greener” (with non-injurious solvents and less hazardous waste)

Fundamental applications

Metathesis is an example of how important fundamental science has been applied for the good of many. “For me,” Grubbs told an interviewer shortly after he was announced as a co-Laureate, “fundamental and applied science seem to flow together. We started out doing very fundamental work — and still do — but I think you also have to keep an eye out for where your research might be useful, and then ‘point it’ in that direction. Once you do that, there are lots of wonderful industrial chemists who will take it and do the applied part.”

Grubbs takes a humble perspective on his role in the breakthrough. “It wasn’t really a ‘discovery,’” he explained to an interviewer in 2005. “It was more a series of changes and additions — finding something and pointing it in new directions. And,” he added with a laugh, “there are still lots of problems out there to solve.”

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