Ei-ichi Negishi, a revolutionary chemist in the field of organometallic chemistry oriented towards organic syntheses, died on June 6 at the age of 85. Negishi pioneered the use of transition metals to break and create covalent bonds. His technique using palladium to catalyze a general reaction, now known as Negishi coupling, won him the Nobel Prize in chemistry in 2010 (shared with Richard F. Heck and Akira Suzuki). This reaction of organozinc reagents with halocarbons has revolutionized the synthesis of natural products, bioactive compounds, drug molecules and molecules for materials science. He was also the first to use zirconium to form a carbon-carbon bond, break a carbon-carbon double or triple bond, and form a carbon-aluminum bond.
Negishi, a Japanese citizen, was born in northern China on July 14, 1935. He obtained a bachelor’s degree in chemistry from the University of Tokyo in 1958 and then joined Teijin, Ltd., where he conducted research on the polymer chemistry. He then moved to the United States on a Fulbright-Smith-Mundt scholarship. In 1963, he received his doctorate in organic chemistry from the University of Pennsylvania. During his graduate studies, he was inspired by a lecture by Herbert C. Brown, one of the two Nobel laureates in chemistry in 1979. After returning to Teijin, Ltd., for 3 years of Plus, Negishi joined Brown’s lab at Purdue University in West Lafayette, Indiana, as a postdoctoral fellow. In 1972 he became an assistant professor at Syracuse University in New York and began his continuing study of reactions catalyzed by transition metals. He returned to Purdue University in 1979 and remained there until his retirement in 2019.
Between 1976 and 1980, Negishi’s research group laid the groundwork for palladium-catalyzed cross-coupling reactions involving reactants of aluminum, zirconium, boron, and zinc that would lead to his Nobel Prize. In addition, he made fundamental contributions to the chemistry of organozirconiums. His group created the highly reactive butene-ZrCp2, now known as Negishi’s reagent. His zirconium catalyzed carboalumination of alkynes and alkenes has reshaped the methods of synthesizing various types of organozirconium and organoaluminum reagents.
I joined Negishi’s group at Purdue University in 1993 as a postdoctoral fellow, although I had known his work from reading his publications on carbopalladation several years before. He really wanted to instill tedious habits in his lab members, who would quickly learn to stay organized and keep detailed documentation. Negishi asked us to analyze the raw reaction mixtures before any means of separation to make sure that we don’t lose useful scientific information, which, he reminded us, could lead to incidental discoveries. Before each group meeting, we had to fill out fact sheets on the results of our recent experiments, which made it easy for Negishi or colleagues to check on our progress. He also instructed us to collect all the hard copies of the raw nuclear magnetic resonance spectra and other characterization data in the order of the corresponding page numbers of the lab notebooks and keep them on file, making them easy to find. His documentation was so well organized that I was able to find collections of my own spectra in his lab when I returned to Purdue University in 2016, nearly two decades after recording this data. In addition to meticulous record keeping, Negishi taught me how to write effective scientific papers by showing unexpected observations to demonstrate originality.
PHOTO: UNIVERSITY OF PURDUE
Always open to unexpected observations from the lab and new ideas from students, Negishi was a great mentor. He taught me that a scientist should only focus on one or two topics and joked that if you have too many children and don’t pay enough attention to them growing up, he may decide to call someone else his father or his mother. By the time I joined his group, there were a lot of chemists working on alkenes and alkynes, so he and I decided to pursue the unpopular topic of allenes. When I left West Lafayette, we both felt that the chemistry of allenes had great potential, and he encouraged me to continue studying them. His advice shaped my career; I have now been studying allenes for over 20 years.
Always energetic, Negishi often took group members on ski trips and eat at local restaurants. He loved Chinese food, but tasting the authentic cuisine during a visit to Shanghai in the early 90s deterred him from the Chinese cuisine available in the United States. He loved to play the piano and was always ready to play a song or two. His favorites were the classics of Beethoven, Bach, Pachelbel and Mozart. He even conducted an orchestra at the closing ceremony of the Pacifichem 2015 conference, the world’s largest meeting place for the chemistry community.
The American Chemical Society awarded Negishi in 1998 the prize for organometallic chemistry and in 2010 the prize for creative work in synthetic organic chemistry. The Royal Society of Chemistry awarded him the Sir Edward Frankland Prize in 2000. He was awarded the Order of Culture of Japan in 2010. These are just a few of the many awards and honors that have recognized his work, which radically changed the way chemists make and break carbon bonds in modern drugs, agrochemicals, and functional materials.
Negishi was curious, frank, fair and always open to debate. Organized and open-minded, he was an admirable role model. His family, students and colleagues will surely be remembered for his characteristic charm and loving nature, and his work will continue to inspire scientists to develop new chemical compounds to improve the lives of human beings.