Nobel chemists change chemical partners

Yves Chauvin of the Institut Français du Pétrole, Rueil-Malmaison, France, Robert H. Grubbs of California Institute of Technology (Caltech), Pasadena, CA, US, and Richard R. Schrock, Massachusetts Institute of Technology (MIT), Cambridge, MA, US, share this year's Nobel prize for chemistry for developing the metathesis method in organic synthesis. David Bradley reports .

All organic substances, by definition contain the element carbon. Carbon has a remarkable ability to form long and short chains and rings, to bond to almost every other element and to link to them and each other through an array of bond types. This chemical affability means not only do carbon compounds form the basis of life on Earth, but they also allow life to synthesise an incredibly rich diversity of molecules. Carbon compounds have also allowed one species in particular to feed itself, change its environment, heal its wounds, and to create in ways almost beyond imagination. This year's chemistry laureates developed a particular way of manipulating carbon compounds, known as metathesis, that has led to yet more opportunities for synthesising a host of novel and useful organic molecules.

Changing places 

Metathesis means 'change places'. In metathesis reactions, double bonds are broken and reformed between carbon atoms in such a way that chemical groups trade places. A generic example might be represented by organic molecules comprised of chemical groups A, B, C, and D: 

A=B + C=D  <--> A=C + B=D 

where B and C have swapped places to create two new products. A specific example would be an alkene metathesis in which side chains on two alkene molecules swap places to produce two new alkenes. Work during the 1950s and 1960s gradually built up a repertoire of such reactions in which the petrochemical feedstock propene, for example, could undergo a switch into ethene and butene, two useful starting materials for polymers. Cyclic alkenes were soon added to the repertoire. 

The go-between for such chemical trade are catalyst molecules, such as metal chlorides and organometallic complexes. In 1970 Chauvin outlined how these metatheses reactions work and what types of metallic compounds might be made that would act as catalysts for these reactions. Until then, chemists had been using a trial and error approach. Chauvin and his colleagues demonstrated that the active form of the catalyst in metathesis was a metal carbene, a compound in which the metal is bound to the carbon with a double bond, and now known as a metal alkylide. 

Chauvin's mechanism explained how they work by invoking a step in which the metal alkylide combines with one of the alkenes to form a ring of four atoms. From this state bonds break and new ones form ultimately shuffling the side chains on the two alkene reactants and spits out the catalyst in its original form. 

With this metathesis 'recipe' in hand, it was Schrock who produced the first highly efficient metallic catalyst for metathesis, based on molybdenum. These catalysts consisted of a central molybdenum atom to which were attached various fluorinated alkyl ether and aromatic groups. These were well- defined structures and provided new clues as to what kinds of modifications of the general structure would lead to a stable and yet active catalyst. 

Grubbs developed the next generation of metathesis catalysts that were not only more efficient, but were also stable in air and worked in water. His first successes were with ruthenium trichloride and its use in polymerising alkenes. In 1992, he and his colleagues reported their first ruthenium-carbene complex, which was stable in the presence of polar solvents and could be used in the polymerisation of another important starting material, norbornene - a precursor for lots of bicyclic molecules in industry, including optical polymers for DVDs. 

The Grubbs and Schrock catalysts offer synthetic chemists countless opportunities. Their widespread use in organic chemistry today arises from the fact they can work with a huge range of chemical groups. That combined with their efficiency and, for Grubbs' catalysts, their ease of handling in air, make them incredibly important. Today, metathesis is used on a daily basis in research laboratories and by the chemical industry, particularly in the development of pharmaceuticals and of advanced plastic materials. 

New designs for metathesis continue apace, with new catalysts emerging on an almost monthly basis. These novel systems are inspired by the need to construct highly complex organic molecules, for example, analogues of natural products with medicinal properties, such as the anticancer drug bryostatin. 

One of the most important aspects of the development of metathesis catalysts is that they are fundamentally more efficient than many other synthetic routes because they require fewer reaction steps and so fewer resources, which means less waste. They are also simpler to use and do not need high temperatures and pressures, which again means lower energy costs. Finally, metathesis reactions do not require toxic solvents and produce less hazardous byproducts than other approaches.