Professor Ei-ichi Negishi together with Professors Richard Heck and Akira Suzuki, received the Nobel Prize in Chemisty 2010 for their work on palladium-catalyzed cross-couplings in organic synthesis.
During Professor Negishi’s recent visit to the Wiley-VCH office (pictured above), Dr. Richard Threlfall spoke with him for ChemViews magazine about his recent research, including the first highly catalytic, highly asymmetric C–C bond-forming reaction, and also about his main goals.
Can you tell us a little bit about your current research?
Shortly after I won the Nobel Prize, I was invited by the Japan Science and Technology Agency (JST), one of the core institutions responsible for the implementation of science and technology policy in Japan, to make suggestions for interesting research topics. I listed up to ten, but in the end I chose three:
The first is carbon dioxide reduction. Of course, CO2 can be reduced with a Grignard reagent easily and completely, and the products are useful energy sources, such as carboxylic acids. But, that is not practical. So we need a catalytic and economical reduction of CO2. This to my knowledge is essentially unknown. Of course, such a catalysis needs a high turnover number of a million, preferably a billion; then we might be in business. So that is one thing.
The second topic I chose was nanomaterials, such as fullerene derivatives, graphene, nanotubes, and so on. I think this field is very promising and almost unlimited. But useful products are still very rare, so I think this area needs to be explored.
And almost in a casual way, I added catalytic asymmetric carbon–carbon bond-forming reactions. This has been one of my hobbies for the last 40 years and in my own group it is becoming better and better. So there is this selfish motivation.
How did you get interested in the area of zirconium?
Yes. Actually I thought about zirconation already in 1978 when we had just discovered the carboalumination of acetylene. Of course, if you add carbon and aluminum to acetylene, then you get an alkenyl aluminum. This turned out to be a synthetically very useful reaction. Then I thought if only we could do the same reaction with alkenes, we would introduce an asymmetric carbon center and this might be a very useful way of asymmetrically making chiral compounds.
The great majority of naturally occurring compounds – organic and bioorganic compounds – are chiral, so we should become very efficient and economical in producing such compounds. But, with regards to this switch from acetylene to alkene, what we were actually dreaming of, at the beginning, is what you might call a one-step Ziegler–Natta polymerization reaction of alkenes. But in a Ziegler-Natta polymerization you want to link as many alkenes as possible. Here, we wanted to just have a one-step reaction. This proved to be very, very difficult.
It took us 17 years. In 1995, to be exact, we came up with what I considered to be a breakthrough in terms of results. Then we started using this reaction, but it was not good enough, not catalytic enough, and so on and so forth.
More recently, as we describe in Chemistry – An Asian Journal, we developed a reaction or process, which we are very, very proud of. It is probably, historically, the first highly catalytic, highly asymmetric C–C bond-forming reaction. This is already very exciting, but, moreover, through the combination of this technology with our previous cross-coupling technology we can now synthesize – I should never say all –, but a wide variety of asymmetric compounds that have been next to impossible to synthesize previously in a highly pure form. All of these very difficult requirements have been fundamentally met.
Exciting stuff!
Purdue University announced the opening of the Negishi–Brown Institute in 2011. Can you tell us a little bit about what has been going on in the last couple of years?
So, when I received my big award I was 75 and several months before that big news I told Purdue University I would retire in five years. This is what we do, particularly in America; you declare when you want to retire. If you don’t want to retire then you don’t have to.
Then the Nobel Prize came, so, the President and the Dean of the School of Science wanted to negotiate with me again. They said “at the moment you are doing half-time research and half-time teaching but you won’t be able to go on like that. So, we will appoint you as Director of this newly formed institute as a half-time appointment. This means there will be no teaching, but only research involved for you.” That meant that I could work more on research, which I always wanted to do, so that was my preference.
Along with that, some organizations, such as Teijin and some universities in Japan, decided to support me and become associated with me. So, I have this kind of arrangement with a couple of universities in Japan. However, I was most enthusiastic about the company I used to work for, Teijin. So 50 long years later, they appointed me as an external research advisor and they asked me to guide some of Teijin’s young chemists. So, typically 2–3 people are coming from Teijin. They have been in some of the top groups in some of the top universities and they are making a series of new discoveries.
Could you tell us one little lesser known fact about Professor Ei-ichi Negishi?
I am what you call a “curious George”, I like many things. You may have heard that I believe there are four things that are important in everybody’s life:
One is health, which I lost when I was around 20, but luckily since then I have been like this, but I have to keep working at it.
The second thing is my family. On this trip I am accompanied by my wife and one granddaughter. I have four grandchildren. During their High School or college years we would like to bring each one of them once to Japan and once to Europe. Europe because it is the home of modern civilization, and to Japan because we have Japanese roots. With four grandchildren this means eight grand trips – this is either the fifth or sixth one. So we are more than half way through.
The third main goal is academic research and then I place my hobby fourth. If you can blend three and four, so that your work becomes your hobby, that would be the ultimate goal.
A perfect combination. Thank you very much for joining us today.
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Ei-ichi Negishi, was born in Hsinking, capital of Manchukuo, now Changchun, China. He was raised in Seoul, Korea, under Japanese rule. In 1958 Negishi graduated from the University of Tokyo, Japan, and became a research chemist at Teijin, Japan. He then obtained a Fulbright All-Expense Scholarship, took a leave of absence from Teijin, and went to the University of Pennsylvania, USA, as a graduate student in 1960. He obtained his Ph.D. degree in 1963 under the supervision of Professor Allan R. Day.
In 1966, he became a postdoctoral researcher at Purdue University, USA, and in 1968 he became an Assistant, working with Nobel Laureate Herbert C. Brown. In 1972, he went on to become Assistant Professor at Syracuse University, USA, where, in 1978, he was promoted to Associate Professor. In 1979, he went back to Purdue University as a Full Professor.
Negishi pioneered the use of organozinc and several other organometallic compounds in palladium-catalyzed cross-couplings with aryl, alkyl, allyl and alkenyl halides.
The Nobel Prize in Chemistry for 2010 jointly went to Professors Ei-ichi Negishi, Richard Heck, and Akira Suzuki for their work on palladium-catalyzed cross-couplings in organic synthesis.
Negishi is a member of the Honorary Board of the Asian Journal of Organic Chemistry.
Selected Awards
- 1996, The Chemical Society of Japan Award
- 1998, Humboldt Senior Researcher Award
- 2000, Royal Society of Chemistry’s Sir Edward Frankland Prize Lectureship
- 2010, Nobel Prize in Chemistry
- Several Honorary Doctor of Science degrees from the Universities of Pennsylvania, Tokyo, Purdue, Syracuse, Hokkaido, Okayama, Wuhan, Three Gorges, Kogakuin, Calcutta, Hunan, and National Taipei University of Technology.
Selected Publications
- Search for Highly Efficient, Stereoselective, and Practical Synthesis of Complex Organic Compounds of Medicinal Importance as Exemplified by the Synthesis of the C21–C37 Fragment of Amphotericin B,
Guangwei Wang, Shiqing Xu, Qian Hu, Fanxing Zeng, Ei-ichi Negishi,
Chem. Eur. J. 2013, 19, 12938–12942.
DOI: 10.1002/chem.201302383 - Widely Applicable Synthesis of Enantiomerically Pure Tertiary Alkyl-Containing 1-Alkanols by Zirconium-Catalyzed Asymmetric Carboalumination of Alkenes and Palladium- or Copper-Catalyzed Cross-Coupling,
Shiqing Xu, Ching-Tien Lee, Guangwei Wang, Ei-ichi Negishi,
Chem. Asian. J. 2013, 8, 1829–1835.
DOI: 10.1002/asia.201300311 - Molecular Tuning of the Closed Shell C–H···F–C Hydrogen Bond,
Norman Lu, Rebecca M. Ley, Charles E. Cotton, Wei-Cheng Chung, Joseph S. Francisco, Ei-ichi Negishi,
J. Phys. Chem. A 2013, 117, 8256–8262.
DOI: 10.1021/jp404791g
Also of Interest
- Nobel Prize in Chemistry,
ChemViews Magazine 2010, October 6
The Nobel Prize in Chemistry for 2010 was awarded to Wiley author Prof. Ei-ichi Negishi along with Richard Heck and Akira Suzuki
