Published online 6 October 2010 | Nature | doi:10.1038/news.2010.511

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Clever coupling catalysts lauded by chemistry Nobel

Chemists honoured for palladium-based compounds that have become ubiquitous in drug manufacture.

Nobel winnersAkira Suzuki, Ei-ichi Negishi and Richard Heck share this year's Nobel Prize in Chemistry.Hokkaido University/ REUTERS; Darron Cummings/ AP Photo ; University of Delaware

A technique that stitches together organic molecules quickly and efficiently — revolutionizing research into drugs, electronics and plastics — has won this year's Nobel Prize in Chemistry.

Richard Heck, Ei-ichi Negishi and Akira Suzuki won the award for their development of reactions that cleanly connect chains of carbon atoms, using small amounts of the metal palladium. The processes they uncovered for forming carbon–carbon bonds in the 1960s and 1970s are now a staple of chemistry textbooks, and are used every day in industry and academia.

The award was uniformly welcomed by organic chemists, who were delighted that the prize committee had chosen to reward what many see as chemistry's core discipline: that of making molecules.

"It's fantastic, well deserved. These processes are the bread and butter of synthetic organic chemists, and these guys were there at the beginning of it all," says Stephen Buchwald at the Massachusetts Institute of Technology, Cambridge, who has himself developed new reactions based on the same approach.

If anything, says Mimi Hii, a synthetic chemist at Imperial College London, the award is overdue. "It's something that everyone has been talking about for years — the only speculation was who was going to get it."

Nobel prizes cannot be awarded posthumously, but others who might have deserved a share of the prize include the late John Stille, who died in a plane crash in 1989.

The start of the revolution

Chemists hoping to attach carbon chains together before the 1970s had a painful task, says Buchwald. Mixing together two compounds would often result in a mess of side-products that would form a sludge at the bottom of a chemist's reaction flask. This was particularly the case for aromatic compounds: those containing rings of carbon atoms sandwiched by doughnut-shaped clouds of their own electrons.

By the 1970s, however, chemists were working on a bevy of reactions to solve this problem. They enlisted organometallic compounds, which combine metals such as palladium with organic molecules based around carbon.

By 1968, Heck — then at the Hercules Chemical Company in Wilmington, Delaware — had found that combining organic molecules with palladium produced a compound that dramatically improved such tricky couplings. The palladium atom, it later emerged, inserted itself between atoms in the carbon–carbon chains as the reaction proceeded, effectively guiding both molecules towards the required product. There were few messy side-reactions.

In the late 1970s, Negishi, of Purdue University in West Lafayette, Indiana, and Suzuki, at Hokkaido University in Sapporo, Japan, published their own variants on this theme, each using different kinds of assisting compounds. "Their contributions have revolutionized organic synthesis," says Ian Paterson, a synthetic organic chemist at the University of Cambridge, UK.

Not just a pretty reaction

It took a decade or so before the chemistry really started to catch the eye of industrial chemists, says Andrew Wells, a chemist at the multinational drug giant AstraZeneca, headquartered in London. He estimates that 15–30% of his company's current portfolio of compounds in development make use of palladium-catalysed cross-coupling reactions.

"We have large internal teams dedicated to this chemistry, and a fair amount of our external science spending goes on collaborations with academic institutions on this technology," says Wells.

Just a few of the molecules made with palladium chemistry include the anti-cancer drug Gleevec (imatinib) and the blood-pressure medication Diovan (valsartan), both made by Swiss-based drug company Novartis, as well as the fungicide boscalid, made by German chemical firm BASF. Palladium catalysts are also key to making organic polymers that conduct electricity — which themselves won the Nobel for chemistry in 2000.

More methods?

This year's prize marks the third time in the past decade that the chemistry Nobel has been awarded for new methods of making molecules. In 2005, it was for metathesis — often described as a molecular dance that couples organic molecules — and in 2001, it was for protocols that allow the manufacture of molecules that are specifically right- or left-handed, known as chiral molecules.

"One of our dreams is to be able to synthesize any organic compound of importance," Negishi told a press conference after he'd received the prize. To those outside the industry, it often seems that with modern methods, chemists can now make any molecule they choose.

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But, says Hii, "There aren't that many methodologies out there that are very robust and very reliable. If we can make a molecule in a week, that is fast — and some total-synthesis groups will still spend years on a molecule. There are still a lot of unknowns in organic chemistry."

The president of the American Chemical Society, Joe Francisco, who is one of Negishi's colleagues at Purdue, adds: "I don't think it's going to be the last Nobel awarded for fundamental work in developing a new form of catalyst." 

  • References

    1. Heck, R. F. J. Am. Chem. Soc. 90, 5535-5538 (1968). | Article
    2. Negishi, E.-I., King, A. O. & Okukado, N. J. Org. Chem. 42, 1821-1823 (1977). | Article
    3. Miyaura, N., Yamada, K. & Suzuki, A. Tetrahedron Lett. 20, 3437-3440 (1979). | Article

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  • #60907

    I think this is a nice and tidy compilation! :-) Even educational.

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