Herbert Newby McCoy Award

1998 McCoy Award Recipient

2010 Nobel Laureate in Chemistry

Ei-ichi Negishi
Professor Chemistry

Ei-ichi Negishi grew up in Japan and graduated in 1958 from the University of Tokyo. He first worked as a research chemist at the Japanese chemical fiber producer, Teijin, Ltd. From 1960 to 1963, while a Fulbright scholar, Negishi earned a Ph.D. in organic chemistry from the University of Pennsylvania. After receiving his doctorate, Negishi resumed his post at Teijin in Japan, but returned to the United States in 1966 for post-doctoral work in organoborane chemistry at Purdue University. After holding a series of academic positions at Syracuse and Purdue, Negishi became a chemistry professor at Purdue in 1979, the position he still holds. Negishi's research has earned him numerous awards and honors, and he has given lectures throughout the world. He has published about 280 scientific papers, several patents, and a few dozen essays.

Abstract of talk

Organic compounds including foods, drugs, clothing, plastics, and construction materials consist mostly of carbon and hydrogen, as well as several other elements such as nitrogen, oxygen, phosphorus, sulfur, and halogens. Most of the other elements in the Periodic Table are so-called metals. Currently, 80-85 elements may be considered to be metals. In earlier days of Grignard reagents and organolithiums, polarization of carbon-metal bonds in the C--M+ sense was considered to be perhaps the most important factor. Then, chemists gradually recognized the significance of empty valence-shell orbitals as Lewis acidic or electrophilic sites that metals can readily provide. The Friedel-Crafts reaction and the hydroboration and other organoboron chemistry developed by H. C. Brown are two representative examples demonstrating the significance of empty orbitals.

With transition metals such as palladium and zirconium that are extensively used in our laboratories, metal-containing species providing simultaneously one or more empty and filled nonbonding orbitals are readily available often as long-lived species. In some fundamental sense, they are like organic singlet carbenes and nitrenes of generally short lives. With both acidic and basic sites that can serve as LUMO (lowest unoccupied molecular orbital) and HOMO (highest occupied molecular orbitals), respectively, many of the transition metal compounds are chemically very versatile, and their chemical processes dominated by low-activation energy concerted processes are generally facile, be they oxidative, reductive, or of non-redox type. This is one of the important bases for their use as catalysts, as opposed to stoichiometric reagents.

Yet another important principle that we and others have begun to fully recognize is the ubiquitous opportunity for activating electrophiles with electrophiles. Whereas the higher acidity of monomeric metal species relative to associated dimers (i.e., one is better than two), has been well recognized and extensively exploited, a seemingly contradictory principle that dimeric species are more acidic than monomers (i.e., two is better than one), has not been well recognized and widely exploited, even though it has been encountered in the Ziegler-Natta reaction and many other acid-catalyzed reactions.

This talk discusses several representative catalytic and stoichiometric reactions involving nickel, palladium, titanium, and zirconium, and illustrates the generalizations presented above.

Research

In 1966, Ei-ichi Negishi began devoting himself to research on organometallic chemistry when he came to Purdue as a postdoctoral associate in Professor H. C. Brown's research group. Negishi participated in Brown's systematic exploration of organoboron chemistry which amply demonstrated the magical power of an empty orbital.

At Syracuse University, Negishi began his career exploring organotransition metal chemistry for organic synthesis. With the recognition that various reactions of 24 d-block transition metals for the formation of carbon-carbon and other types of bonds can be classified into just a few to several fundamentally discrete patterns, i.e., (1) reductive elimination, (2) carbometallation and related addition reactions, (3) migratory insertion, and (4) nucleophilic and electrophilic attack on ligands, he initially focused his attention on reductive elimination, and developed the nickel-catalyzed cross-coupling reaction of organoaluminums. This led to the discovery of the corresponding palladium-catalyzed organoaluminum reaction in 1976. Negishi's systematic exploration led to findings on palladium-catalyzed cross-coupling reactions of organometals containing aluminum, magnesium, zinc, and zirconium, thus establishing one of the most straightforward and versatile methods for the construction of organic compounds, before a number of his followers, notably J. K. Stille and A. Suzuki, began developing related methods involving tin, boron, and other metals.

While Negishi's efforts regarding Pd- or Ni-catalyzed cross coupling continue, in 1978 he began publishing in his second major area of research - carbometallation of alkynes and alkenes. The following five represent his major contributions in this area:

1. Zirconium-catalyzed carboalumination of alkynes (since 1978),
2. Zirconium-catalyzed enantioselective carboalumination of alkenes (since 1995),
3. Zirconium-promoted cyclization reac- tions of alkenes and alkynes (since 1985),
4. Palladium-catalyzed cyclic cascade carbopalladation (since 1988), and
5. Palladium-catalyzed cyclic acylpalladation (since 1983).

In the Zr-catalyzed carboalumination and related reactions, a potentially general and synthetically important principle of activation of electrophiles by electrophiles through dimeric association (two is better than one) has emerged. This concept has not only promoted the discovery and development of catalytic bimetallic reactions but also helped delineate mechanisms of zirconium- and titanium-catalyzed processes. Negishi's contributions in the area of carbometallation are easily as important as those on reductive elimination, and their widespread applications by others similar to the case of palladium-catalyzed cross coupling appear to be imrninent.

More recently, Negishi and his research group are discovering and developing novel migratory insertion reactions of organozirconium and other organometallic species other than widely known carbonylation. This is one area of research Negishi hopes to pursue over the next several years.