There are a family of coupling reactions in which a organometallic reagent (typically a Sn, B, Zn or Mg reagent) is treated with an electrophile (usually an iodide, bromide, or triflate) in the presence of a Pd catalyst, to form cross-coupled products. These reactions are of such importance that each of the organometallic reagent couplings is a separate name reaction, organostannane couplings are Stille reactions, organoborane couplings are Suzuki reactions, organozinc couplings are Negishi reactions, and organomagnesium couplings are Kumada reactions.
Mechanism: All of these reactions proceed by a common mechanism. The process is initiated by reaction of the Pd(0) species with the halide to form a Pd(II) alkyl iodide (Pd(0) should be considered a nucleophile, and a reducing reagent, much in the way Mg° is in the formation of a Grignard reagent). After this oxidative addition the Pd(II) species (which is now a Pd electrophile) performs a transmetalation on the organometallic component -- a Pd/Sn, Pd/B or Pd/Zn exchange -- to form a diorganopalladium (II) intermediate. This species then undergoes a reductive elimination to form the C-C bond, and return the catalyst to the Pd(0) oxidation state. If a Pd-catalyzed cross-coupling is performed under a CO atmosphere then there may be a C=O insertion, such that both fragments become substituents on a ketone (carbonylative coupling).
Each of the metals has advantages and disadvantages in their use.
Stille couplings (Pd/Sn) work well, and organotin compounds are the only organometallic coupling partners that can be purified easily, and they can be stored. However organotin compounds are toxic, and the separation of products from starting materials and byproducts can be very difficult. They are also poorly suited for alkyl couplings, since there are typically several alkyl group on tin. In fact, alkyl couplings are generally problematic, because of potential β-hydride eliminations in either of the two Pd(II) intermediates.
Suzuki couplings (Pd/B), are usually done using R'-B(OR)2 compounds but they work well even with trialkyl boranes. The alkenyl and alkyl borate starting materials can often be easily made by hydroboration reactions. However, they do require the presence of base to form the boron ate complexes, and organoboranes are too reactive for easy purification. However, left-over starting organoborates, and other byproducts can often be easily removed because of their polar nature.
Negishi couplings (Pd/Zn) show excellent reactivity, but the organozinc compounds show less functional group compatibility because of their higher reactivity, and the higher reactivity of the Li and Mg reagents often used to prepare them. They seem to be especially well suited for alkyl couplings
In 1971, American chemist Richard F. Heck discovered a previously unknown carbon-carbon bond-forming reaction mediated by palladium, which forms substituted olefins. In his report for the Journal of the American Chemistry Society, Heck wrote that "in spite of some limitations, the organic halide olefinic substitution reaction should prove to be a useful synthetic reaction", which is something of an understatement. Now called the Heck reaction (or the Heck-Mizoroki reaction, for Tsutomu Mizoroki, who detailed a related reaction independently), this process set the framework for countless refinements and extensions to the catalytic organometallic bond forming processes for organic synthesis.
Heck pioneered his field of study virtually alone, with seven sole-author papers in the 1960s, one of which inspired Mizoroki's experiment. He was the first chemist to explain the co-catalyzed hydroformylation reaction, the mechanism which drives all catalytic organometallic reactions. He later taught at the University of Delaware, but retired with some frustration in 1989 when his funding was canceled and he was unable to obtain corporate or government grants to further his research. In retirement he was once quoted as saying, "I'm not doing any chemistry anymore, but I think I've done my share".
Ei-ichi Negishi "pronounced: Ei-ichi (Â-E-chE) Negishi (Na-gE-shE)" was Born in 1935, Negishi came to the United States in 1960 after graduating from the University of Tokyo.
In 1962, while studying for his doctorate at the University of Pennsylvania, he met Purdue chemistry professor Herbert C. Brown—a pioneer in synthetic organic chemistry. Negishi admired Brown’s research and predicted,
He then moved to Syracuse University where he served as an assistant professor (1972-76) and associate professor (1976-79).
Dr. Negishi joined the faculty at Purdue in 1979—the same year Brown was awarded the Nobel Prize in Chemistry—and has been a researcher in this building for more than thirty years.
• Fulbright-Smith-Mund All Expense Scholarship, 1960-63
• J. S. Guggenheim Memorial Foundation Fellowship, 1987
• A. R. Day Award, 1996
• Chemical Society of Japan Award, 1996
• American Chemical Society Organometallic Chemistry Award, 1998
• Herbert N. McCoy Award - Purdue University, 1998
• Alexander von Humboldt Award, Senior Researcher Germany, 1998-2001
• Herbert C. Brown Distinguished Professor - Purdue University, 1999
• Sir Edward Frankland Prize Lectureship, 2000
• Citation of Negishi Cross-Coupling - Merck Index, 13th Ed., 2001
• Sigma Xi Award - Purdue Univeristy, 2003
• Gold Medal of Charles University, Prague, Czech Republic, 2007
• Yamada-Kaga Prize, 2007
• American Chemical Society Award for Creative Work in Synthetic Organic Chemistry, 2010
• Nobel Prize in Chemistry, 2010
• Japanese Person of Cultural Merit, 2010
• Japanese Order of Culture, 2010
• Sagamore of the Wabash, State of Indiana, 2011
• Order of the Griffin, Purdue University, 2011
• American Academy of Arts & Sciences, 2011