Ei-ichi Negishi, a groundbreaking chemist in the field of organometallic chemistry directed toward organic syntheses, died on 6 June 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 the Negishi coupling, earned him the Nobel Prize in Chemistry in 2010 (shared with Richard F. Heck and Akira Suzuki). This reaction of organozinc reagents with halocarbons revolutionized the syntheses of natural products, bioactive compounds, drug molecules, and molecules for materials sciences. He also pioneered the use of 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 14 July 1935. He received a bachelor’s degree in chemistry from the University of Tokyo in 1958 and subsequently joined Teijin, Ltd., where he conducted research on polymer chemistry. He then moved to the United States on a Fulbright-Smith-Mundt scholarship. In 1963, he received his PhD in organic chemistry from the University of Pennsylvania. During his graduate studies, he was inspired by a lecture by Herbert C. Brown, one of two 1979 Nobel laureates in chemistry. After returning to Teijin, Ltd., for 3 more years, 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 lifelong study of transition metal–catalyzed reactions. 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 foundation for the palladium-catalyzed cross-coupling reactions involving aluminum, zirconium, boron, and zinc reagents that would lead to his Nobel Prize. In addition, he made seminal contributions to organozirconium chemistry. His group created the highly reactive butene-ZrCp2, now known as the Negishi reagent. His zirconium-catalyzed carboalumination of alkynes and alkenes has reshaped the methods for the syntheses of various types of organozirconium and organoaluminum reagents.
I joined Negishi’s group at Purdue University in 1993 as a postdoctoral fellow, although I had been familiar with his work since reading his publications on carbopalladation several years earlier. He was serious about instilling fastidious habits in his lab members, who would quickly learn to stay organized and keep detailed documentation. Negishi required us to analyze crude reaction mixtures before any means of separation to ensure that we did not lose useful scientific information, which, he reminded us, could lead to serendipitous discoveries. Before every group meeting, we were required to fill out information sheets on the results of our recent experiments, making it easy for Negishi or colleagues to check our progress. He also instructed us to collect all the hard copies of crude nuclear magnetic resonance spectra and other characterization data in the order of the corresponding laboratory notebook page numbers and keep them in file folders, making them easy to find. His documentation was so well organized that I could find collections of my own spectra in his laboratory when I returned to Purdue University in 2016, almost two decades after recording those data. In addition to meticulous record-keeping, Negishi taught me how to write effective scientific papers by showing unexpected observations to demonstrate originality.
PHOTO: PURDUE UNIVERSITY
Always open to unexpected observations from the lab and new ideas from students, Negishi was an excellent mentor. He taught me that a scientist should focus on just one or two topics and joked that if one has too many children and does not pay enough attention to them as they are growing up, they might decide to call someone else their father or mother. At the time I joined his group, many chemists were 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 molded my career; I have now been studying allenes for more than 20 years.
Always energetic, Negishi often took group members on skiing excursions and out to eat at local restaurants—he enjoyed Chinese food, but tasting the authentic cuisine during a visit to Shanghai in the early 1990s put him off the Chinese food available in the United States. He loved playing the piano and was always ready to perform a piece or two. His favorites were classics by Beethoven, Bach, Pachelbel, and Mozart. He even conducted an orchestra during the closing ceremony of the Pacifichem 2015 conference, the world’s largest meeting of the chemistry community.
The American Chemical Society honored Negishi in 1998 with the Award in Organometallic Chemistry and in 2010 with the Award for Creative Work in Synthetic Organic Chemistry. The Royal Society of Chemistry awarded him the Sir Edward Frankland Prize in 2000. He received Japan’s Order of Culture in 2010. These are just a few of the many awards and honors that recognized his work, which so drastically changed the way chemists make and break the carbon bonds in modern medicines, agrochemicals, and functional materials.
Negishi was curious, frank, fair, and always ready to debate. Organized and open-minded, he was an admirable role model. He will surely be remembered by his family, students, and colleagues for his characteristic charm and loving nature, and his work will continue to inspire scientists to develop new chemical compounds to better the lives of human beings.
