Interview: A catalytic lifetime

Bob Grubbs talks to Alison Stoddart about the beginnings of organometallic chemistry and his search for the next catalyst

Bob Grubbs

Bob Grubbs is the Victor and Elizabeth Atkins professor of chemistry at California Institute of Technology, US. His research spans organometallic, organic synthetic, mechanistic and polymer chemistry. He is renowned for the development of the Grubbs' catalyst for the metathesis reaction for which he shared the Nobel Prize in Chemistry in 2005.

What attracted you to chemistry and then to specialise in organometallic chemistry?
It was making things and mechanistic ideas that attracted me to chemistry. The idea that you can do simple experiments and understand what is happening at the molecular level is fascinating.

Early on, I was encouraged by Merle Battiste and Ron Breslow, both physical organic chemists. But at the time, there were many smart people doing physical organic chemistry and there was this new field called organometallic chemistry. There were few people looking at the mechanistic side and it looked like an area where you could take the tools of physical organic chemistry and solve problems. Plus, it looked like it could be a good way to make new reagents for organic reactions. And you could get into the field real fast - you only had to read three papers and you were an organometallic chemist! Just before graduate school, I heard a talk by one of my heros, Rolli Pettit. He made me think about using metals in organic chemistry.

Then, I went to postdoc with Jim Collman who had come into organometallic chemistry from the organic side - I learned a lot from him.

Why was the Grubbs' catalyst such a hit?
Basically, carbon-carbon double bonds are in everything we use. So a reaction that makes carbon-carbon double bonds in a fast and efficient way is useful in many areas of chemistry; from pharmaceuticals to polymers. The catalyst provided synthetic organic chemists with a new way of cutting up molecules and gave polymer chemists a new way of making polymers.

Did you think the Grubbs' catalyst would have the impact it did?
I had no clue. There were hints but I didn't expect the community to adopt it so fast. But it is a simple dissection that is easy for people to see. Also, I underestimated the creativity of the chemical community and their ability to find new applications so rapidly.

Why has the Grubbs' catalyst evolved over several generations?

Now, there are about 15 different variations of the catalyst, all of which have slightly different features. The latest, the third generation catalyst, opens up many new possibilities.

Do you have anymore goals for the metathesis reaction?
I would like to have a catalyst that lives forever! We still have lifetime issues and we are trying to make the catalysts more stable. It is dependent on the system - for cross-coupling metathesis reactions the efficiency is good but ring-closing reactions need high dilution and the efficiency drops off. This type of problem gives us an excuse to do mechanistic studies - we try to understand how the catalysts decompose and then design ligands to prevent this.

The other part is control of stereochemistry. We are trying to find a catalyst that can control the E/Z geometry of a double bond in simple molecules. I joke that I can't retire until I do that!

What other projects are you working on?
In collaboration with an ophthalmologist, we are working in the area of biomaterials. The project involves making intraocular lenses from silicon polymers that are implanted after cataract surgery. The lenses are light adjustable so they are easily corrected after implantation. We have one product that is currently in human trials.

On the synthetic side, we have just purchased a robot to screen for new catalysts. We are focusing on fundamental transformations, like the metathesis reaction, which are in need of a good catalyst. The robot lets us to run millions of reactions in a short time. If it took me 35 years to find the metathesis catalyst, I probably don't have another 35 years to find the next, so this is where the robot comes in!

What are the challenges facing the synthetic chemistry community at the moment?

What's the most difficult research problem you have had to overcome?
In the research we do, you make a hundred little decisions that lead you along a path and when you look back, you realise you have made a big decision, but there was never one instant where you made it. That's the way science goes. Some people have asked how I had the patience to work on one problem for 35 years and it's actually not long term patience but short term impatience ... I was impatient for the next step.

If you weren't a scientist what would you do?
I joke about being a mountain guide. I used to rock-climb a lot and now I enjoy walking and climbing hills. I would like to do something outdoors.

What did it feel like to win a Nobel Prize?
A large number of feelings - excitement, pleasure, total shock and surprise ... and then you get on with life. My wife claims that we drink better wine and dance more!

Related Links

Enhanced selectivity in the conversion of methanol to 2,2,3-trimethylbutane (triptane) over zinc iodide by added phosphorous or hypophosphorous acid
John E. Bercaw, Robert H. Grubbs, Nilay Hazari, Jay A. Labinger and Xingwei Li, Chem. Commun., 2007, 2974
DOI: 10.1039/b705470j