Asymmetric catalysis enables selective synthesis
Professor Nicolai Cramer of the Ecole Polytechnique Fédérale in Lausanne received this year’s BASF Catalysis Award at the Heidelberg Forum of Molecular Catalysis today. Professor Cramer, who was born in Stuttgart in 1977, received the award for his work on catalytic processes used to synthesize biologically active molecules. Professor Cramer is the head of the laboratory for asymmetric catalysis and synthesis in Lausanne. The BASF Catalysis Award is worth € 10 000. The science journalist Klaus Jopp interviewed Professor Cramer and found out what asymmetric catalysis actually is and why it can have an important effect on everyone's life.
Professor Cramer, congratulations on winning the BASF Catalysis Award in 2013! How important is catalysis in the field of chemistry and what new developments do you expect to see over the next few years?
Catalysis is already a very important process. Nowadays, more than 90 percent of all chemical products come into contact with a catalyst at least once during their manufacture. This is a trend that can be observed world-wide, and it will certainly continue.
The prize was awarded to you for the asymmetric catalysis of biologically active molecules. What is asymmetric catalysis?
In asymmetric catalysis, we use chiral metal complexes to control syntheses in such a way that they become enantioselective. This allows us to produce only one version of two molecules that are a mirror image of each other.
Your work is concerned with the direct functionalization of C-H bonds. Why is this so important and how do you go about this?
C-H bonds are very widespread. In the field of organic chemistry, there is hardly a single molecule that does not contain several of these bonds. However, the reactivity of these bonds is very low, and compounds such as paraffins are largely inert. It is therefore difficult to make use of these bonds in syntheses, but we can observe in nature that certain enzymes can indeed make this possible. The targeted functionalization of these bonds provides enormous benefits, simply because the spectrum of raw materials that can be used in chemistry is very much wider. Another advantage is the higher efficiency that can be achieved compared to existing methods of synthesis, which require several steps. In particular, we have to pay attention to the selectivity of the reactions to ensure that they occur at exactly the right place. We can achieve this by using the appropriate catalysts to activate an increasing variety of C-H bonds for use in chemical syntheses.
This type of catalysis is used to selectively produce single enantiomers. Why is this so important?
The demand for molecules of this type has been constantly increasing over the past few years. One of the reasons for this is that the two enantiomers of the same drug often have different or even conflicting modes of action. The tragic events surrounding the sedative thalidomide show what can happen if we do not pay attention to this.
The bonds are activated with tailor-made transition metal complexes. Do the ligands play a decisive role?
We have succeeded to a certain extent in achieving the reactivity and selectivity we require by using tailor-made complexes. There are several different ways to achieve this: we can look at the central metal atom or, more importantly, we can look at the ligands that surround the metal atom. We will certainly continue to take this approach in future. Indeed, it can be said that the development of the ligands is the royal league. It is often absolutely essential to have the right ligand in order to obtain the required reactivity and selectivity or to steer the reaction in the right direction. For instance, the development of special phosphine ligands has enabled us to make use of reactions that were previously impossible.
Is it already possible to “design” the required ligands?
No, we have not yet reached the point at which this works perfectly every time. It requires a mixture of rational design, iterative screening, and a tiny bit of luck. Sometimes chance also plays a part. For instance, when materials unintentionally become contaminated and this surprisingly turns out to be very useful. But this only ever becomes apparent at a later stage.
Optimizing reactions, establishing a broader and better raw material base – is this an example of sustainability in action, which is increasingly gaining importance in the field of chemistry?
There has been a great deal of interest in this topic over the past few years, especially from the point of view of sustainability. Catalysis is the decisive tool here. One way to describe it: It offers us a shortcut to sustainability.
Is sustainability an important issue for you?
Our main goal is to make reactions quicker, better and more economical – by doing so, we automatically contribute to sustainability.
Although you are deeply involved in fundamental research, do you have any idea what practical benefits your research will bring in future?
We develop precision tools for all fields in which molecules are synthesized. Our methods can be used to speed up the synthesis of chemical compounds. In medical research, the aim is to gain access to potential active ingredients more quickly. For instance, we have synthetized and identified molecules that are active against HIV. Here in Lausanne, we work closely together with the life sciences. There are also some other interesting areas of research in fields such as material sciences, because we can provide better access to molecules for use in applications such as organic electronics.
Up until now, the separation of racemic mixtures has been complicated and expensive. Does your work offer an alternative?
Very great progress has been made in recent years in the physical separation of racemic mixtures. Our approach is valuable if you know which of the two entianomers you wish to use. You then no longer have to throw half of the molecules away.
Do you also work together with BASF?
Up until now, there have not been any projects or direct cooperation with BASF. Indirectly, I support the company by training good doctoral students, who are now working at BASF.
What do you do in your free time when you are not researching in the laboratory?
I enjoy the wonderful nature around the city of Lausanne. Sport plays an important part, especially running, squash and various winter sports, and, like nearly all chemists, I also enjoy cooking very much. The laboratory and the kitchen seem to have a great deal in common.