Ei-ichi Negishi

Ei-ichi Negishi
Negishi in 2010
Ei-ichi Negishi
Born	14 7, 1935
Birthplace	Xinjing, Manchukuo
Died	Template:Death date and age Indianapolis, Indiana, United States
Nationality	Japanese
Occupation	Chemist, academic
Title	Herbert C. Brown Distinguished Professor
Employer	Purdue University
Known for	Negishi coupling, ZACA reaction
Education	Ph.D., University of Pennsylvania (1963)
Spouse(s)	Sumire Suzuki (m. 1959; died 2018)
Children	2
Awards	Nobel Prize in Chemistry (2010), Order of Culture (2010), Person of Cultural Merit (2010)
Website	[https://www.chem.purdue.edu/activity/public/profile/chem/negishi Official site]

Ei-ichi Negishi (根岸英一, Negishi Eiichi; 14 July 1935 – 6 June 2021) was a Japanese chemist whose pioneering work on palladium-catalyzed cross-coupling reactions transformed the practice of organic synthesis and earned him a share of the 2010 Nobel Prize in Chemistry. Born in the Japanese puppet state of Manchukuo and raised in post-war Japan, Negishi built a career spanning more than five decades, the majority of which was spent at Purdue University in the United States, where he held the position of Herbert C. Brown Distinguished Professor and served as director of the Negishi-Brown Institute. The reaction that bears his name — the Negishi coupling — became one of the most important tools in modern chemistry, with estimates suggesting it is employed in at least one-quarter of all reactions in the pharmaceutical industry. He shared the Nobel Prize with Richard F. Heck and Akira Suzuki "for palladium catalyzed cross couplings in organic synthesis." Negishi died on 6 June 2021 at the age of 85 in Indianapolis, Indiana.

Early Life

Ei-ichi Negishi was born on 14 July 1935 in Xinjing (present-day Changchun, China), the capital of Manchukuo, a Japanese puppet state in northeast China that existed from 1932 to 1945. His family was among the many Japanese civilians living in Manchukuo during the period of Japanese imperial expansion in East Asia. Following Japan's defeat in World War II and the dissolution of Manchukuo in 1945, the Negishi family returned to Japan, where Ei-ichi grew up during the turbulent post-war reconstruction period.

Negishi was raised in Japan and developed an early interest in science. He later recalled that as a young man growing up in post-war Japan, he was influenced by the country's rapid modernization and the importance placed on scientific and technological advancement in the rebuilding effort. His formative years in Japan shaped his determination to pursue a career in the sciences, and he proved to be an exceptionally capable student, eventually gaining admission to the University of Tokyo, one of Japan's most prestigious academic institutions.

Education

Negishi pursued his undergraduate studies at the University of Tokyo, where he earned his bachelor's degree in chemistry. The University of Tokyo provided him with a strong foundation in organic chemistry and exposed him to the rigor of Japanese academic science. After completing his undergraduate education, Negishi initially entered the Japanese workforce, joining the chemical company Teijin, where he gained early industrial experience in chemistry.

Seeking to advance his knowledge and pursue original research, Negishi traveled to the United States to undertake graduate studies. He enrolled at the University of Pennsylvania, where he studied under the supervision of Allan R. Day. His doctoral research focused on the basic cleavage of arylsulfonamides and the synthesis of bicyclic compounds derived from piperazine containing bridgehead nitrogen atoms. He completed his Ph.D. in 1963. The decision to pursue graduate education in the United States was a pivotal moment in Negishi's career, as it placed him within the American academic system where he would spend the remainder of his professional life and where he would conduct his most important scientific work.

Career

Early Career and Work with Herbert C. Brown

After completing his doctoral studies at the University of Pennsylvania in 1963, Negishi began his academic career in the United States. He joined Purdue University as a postdoctoral researcher, where he had the opportunity to work with Herbert C. Brown, the renowned organoborane chemist who would himself go on to win the Nobel Prize in Chemistry in 1979. Working alongside Brown at Purdue was formative for Negishi, as it immersed him deeply in the field of organometallic chemistry — the study of chemical compounds containing bonds between carbon and metal atoms. Brown's laboratory was one of the world's leading centers for research on the use of organoboron and organoaluminum compounds in organic synthesis, and Negishi absorbed the intellectual framework that would guide his own subsequent investigations.

Negishi subsequently moved to Syracuse University, where he held a faculty position and began to develop his independent research program. At Syracuse, he started to explore the potential of transition metals — particularly palladium and nickel — as catalysts for forming carbon-carbon bonds, a line of inquiry that would become the central focus of his career.

Return to Purdue University

In 1979, Negishi returned to Purdue University, where he would remain for the rest of his career. He was appointed to a professorship in the Department of Chemistry and, over the decades that followed, rose to become one of the university's most distinguished faculty members. He eventually held the title of Herbert C. Brown Distinguished Professor of Chemistry, a named chair honoring his former mentor. He also served as director of the Negishi-Brown Institute at Purdue, a research center dedicated to advancing the field of organometallic chemistry and its applications in organic synthesis.

At Purdue, Negishi built a productive and influential research group, training numerous graduate students and postdoctoral researchers who would go on to make their own contributions to the field. Among his doctoral students was James M. Tour, who became a prominent chemist in his own right, known for his work in nanotechnology and molecular electronics.

The Negishi Coupling

The work for which Negishi is best known — the Negishi coupling reaction — was developed during the late 1970s and represented a major advance in the ability of chemists to construct complex organic molecules. The Negishi coupling is a palladium- or nickel-catalyzed cross-coupling reaction that forms carbon-carbon bonds between an organozinc compound and an organic halide or similar electrophilic substrate.

The formation of carbon-carbon bonds is one of the most fundamental challenges in organic chemistry, as the ability to join carbon atoms together in controlled and predictable ways is essential for building the complex molecular architectures found in pharmaceuticals, agrochemicals, natural products, and advanced materials. Before the development of modern cross-coupling methods, chemists had limited tools for forming these bonds selectively and efficiently, particularly when the target molecules contained sensitive functional groups that could be damaged by harsh reaction conditions.

The Negishi coupling offered several advantages over other cross-coupling methods. The use of organozinc reagents provided a balance of reactivity and selectivity — they were reactive enough to participate efficiently in the catalytic cycle but stable enough to tolerate a wide range of functional groups. This made the Negishi coupling applicable to a broad spectrum of substrates and allowed chemists to construct molecules of considerable complexity in fewer synthetic steps.

Negishi's work on palladium-catalyzed cross-coupling was part of a broader revolution in organic synthesis that took place during the 1970s and 1980s. The Negishi coupling, along with the Heck reaction developed by Richard F. Heck and the Suzuki reaction developed by Akira Suzuki, collectively provided chemists with a powerful toolkit for building carbon-carbon bonds using palladium catalysis. These three reactions, while each employing different organometallic partners (organozinc for Negishi, alkenes for Heck, and organoboron for Suzuki), shared the common feature of palladium-catalyzed activation and bond formation.

The practical impact of these cross-coupling reactions on the chemical and pharmaceutical industries was immense. According to estimates cited in Nature, the Negishi coupling is used in at least one-quarter of all reactions in the pharmaceutical industry, reflecting its central role in the synthesis of drug candidates and active pharmaceutical ingredients. The reaction has also found applications in the synthesis of organic light-emitting diode (OLED) materials, agrochemicals, and other industrially important compounds.

The ZACA Reaction

Beyond the Negishi coupling, Negishi made significant contributions to other areas of organometallic chemistry. He developed the ZACA (Zirconium-catalyzed Asymmetric Carboalumination of Alkenes) reaction, another important methodology in organic synthesis. The ZACA reaction allows for the enantioselective addition of carbon groups to alkenes using zirconium catalysis, enabling the construction of chiral centers with high selectivity. This reaction expanded the scope of catalytic methods available for asymmetric synthesis, an area of critical importance in pharmaceutical chemistry, where the three-dimensional arrangement of atoms in a drug molecule can determine its biological activity and safety profile.

Broader Contributions to Organometallic Chemistry

Throughout his career, Negishi published extensively and contributed to the broader theoretical and practical understanding of transition-metal-catalyzed reactions. He authored and edited several influential textbooks and monographs on organometallic chemistry, which served as standard references for generations of chemists. His research program at Purdue encompassed a wide range of topics within organometallic chemistry, including the development of new catalytic systems, the exploration of reaction mechanisms, and the application of metal-catalyzed methods to the total synthesis of natural products and other complex molecules.

Negishi was also known for his advocacy of the importance of catalysis in addressing global challenges. In later years, he spoke publicly about the potential of catalytic chemistry to help reduce carbon dioxide emissions and address environmental problems. In one notable statement, he declared: "We must find an economic way to reduce CO2 emissions by using catalysts."

Affiliations

In addition to his long tenure at Purdue University, Negishi maintained connections with Japanese academic institutions. He held an affiliation with Hokkaido University in Japan, reflecting his continued engagement with the Japanese scientific community even as he spent the majority of his career in the United States. His earlier career also included time at Teijin, the Japanese chemical company where he worked before pursuing his doctorate, and at Syracuse University, where he held a faculty position before returning to Purdue.

Personal Life

Ei-ichi Negishi married Sumire Suzuki in 1959, and the couple had two children together. Sumire Negishi died in 2018.

Negishi was known among colleagues for his warmth, dedication to mentoring younger scientists, and deep commitment to his research. An anecdote widely shared after his Nobel Prize win noted that Negishi carried his Nobel gold medallion in his wallet — an unusual practice among Nobel laureates that reflected his pride in the achievement and his characteristically unpretentious manner.

Negishi retained his Japanese nationality throughout his life, even as he spent the majority of his career in the United States. He maintained strong ties to Japan and was recognized by the Japanese government with several of its highest cultural honors following his Nobel Prize.

Negishi died on 6 June 2021 at the age of 85 in Indianapolis, Indiana. According to the Proceedings of the National Academy of Sciences, the cause of death was pneumonia following surgery.

Recognition

Negishi received numerous awards and honors throughout his career, culminating in the 2010 Nobel Prize in Chemistry. He shared the prize with Richard F. Heck and Akira Suzuki "for palladium catalyzed cross couplings in organic synthesis," a recognition that the three chemists' collective work had fundamentally transformed the practice of synthetic chemistry.

Prior to the Nobel Prize, Negishi received the Sir Edward Frankland Prize Lectureship from the Royal Society of Chemistry in 2000, an award recognizing outstanding contributions to organometallic chemistry or related fields.

Following the announcement of his Nobel Prize, the Japanese government honored Negishi with two of its most prestigious cultural awards: the Person of Cultural Merit (文化功労者) designation and the Order of Culture (文化勲章), both conferred in 2010. These awards recognized his contributions to science as achievements of national significance for Japan.

In 2012, Negishi was elected as an Honorary Fellow of the Royal Society of Chemistry, alongside his fellow Nobel laureate Akira Suzuki, further recognizing the lasting significance of their contributions to the chemical sciences.

At Purdue University, Negishi's contributions were recognized through his appointment as the Herbert C. Brown Distinguished Professor of Chemistry, one of the most honored faculty positions in the department, named after his own mentor. The Negishi-Brown Institute at Purdue, which he directed, further cemented his association with the university and its tradition of excellence in organometallic chemistry.

Legacy

Ei-ichi Negishi's legacy in chemistry rests on his foundational contributions to the development of palladium-catalyzed cross-coupling reactions, which transformed the way chemists construct complex organic molecules. The Negishi coupling, along with the related Heck and Suzuki reactions, constituted what the Nobel Committee described as one of the most important advances in organic synthesis in the twentieth century.

The practical impact of these reactions has been felt across multiple industries. In the pharmaceutical sector, palladium-catalyzed cross-coupling reactions, including the Negishi coupling, became standard tools for the construction of drug molecules. The estimate that at least one-quarter of all reactions in the pharmaceutical industry employ some form of cross-coupling underscores the centrality of these methods to modern drug development. The reactions have also been applied in the development of organic electronic materials, including OLED displays, and in the synthesis of agrochemicals and advanced polymers.

Beyond his specific chemical discoveries, Negishi's legacy encompasses his decades of mentorship and training of younger scientists at Purdue University. The students and postdoctoral researchers who passed through his laboratory went on to populate academic and industrial positions around the world, extending the influence of his research program well beyond his own publications. His doctoral student James M. Tour, for example, became a noted figure in nanotechnology, carrying forward the tradition of innovative chemical research that Negishi embodied.

Negishi's career also represented a significant chapter in the history of Japanese scientific achievement on the international stage. As a Japanese national who spent the majority of his career in the United States, he served as a bridge between the American and Japanese scientific communities. His Nobel Prize, along with that of Akira Suzuki, was celebrated in Japan as a source of national pride and as evidence of the continuing strength of Japanese contributions to the global scientific enterprise.

At Purdue University, the Negishi-Brown Institute continues to serve as a center for research in organometallic chemistry and catalysis, ensuring that the intellectual tradition established by Negishi and his mentor Herbert C. Brown endures beyond their lifetimes. The reactions that Negishi developed remain essential tools in the modern chemist's repertoire, and their continued use in laboratories and manufacturing plants around the world constitutes perhaps the most tangible and enduring aspect of his scientific legacy.