Editor’s
EDITOR-IN-CHIEF
Laura L. Kiessling University of Wisconsin, Madison BOARD OF EDITORS
Jennifer A. Doudna University of California, Berkeley
Kai Johnsson Ecole Polytechnique Fe´de´rale de Lausanne
Anna K. Mapp University of Michigan, Ann Arbor
Michael A. Marletta University of California, Berkeley
James R. Williamson The Scripps Research Institute EDITORIAL ADVISORY BOARD
Carolyn R. Bertozzi University of California, Berkeley
Brian T. Chait Rockefeller University
Tim Clackson ARIAD Pharmaceuticals, Inc.
Jon C. Clardy Harvard Medical School
Benjamin F. Cravatt The Scripps Research Institute
Peter B. Dervan California Institute of Technology
Rebecca W. Heald University of California, Berkeley
Tony Hunter Salk Institute
Richard H. Kramer University of California, Berkeley
Rolf Mu¨ller Saarland University/Helmholtz Institute for Pharmaceutical Research Saarland
Joseph P. Noel Howard Hughes Medical Institute, The Salk Institute for Biological Studies
Thomas V. O’Halloran Northwestern University
Hiroyuki Osada RIKEN
Anna M. Pyle Yale University
Ronald T. Raines University of Wisconsin, Madison
Charles Sawyers University of California, Los Angeles
Stuart L. Schreiber Harvard University
Carsten Schultz EMBL
Peter G. Schultz The Scripps Research Institute
Michael P. Sheetz Columbia University
H. Ulrich Stilz Sanofi-Aventis, Frankfurt
Hiroaki Suga The University of Tokyo
Wilfred A. van der Donk Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign
Christopher T. Walsh Harvard Medical School
www.acschemicalbiology.org
LETTER Nobel Carbon, a Worthy Element
T
he ability of carbon to form long and stable carbon⫺carbon bonds underpins the existence of all known living systems. This property allows for the formation of a countless number of diverse compounds. While Nature determined ways to synthesize complex carbon-based compounds well before life existed, reproducing the same fundamental reaction in a test tube remained elusive until relatively recently. Now, the carbon⫺carbon bond-forming reaction is an essential step in the synthesis of valuable commodities, including drugs, plastics, and electronics, thanks in part to the pioneering work in palladium-based catalysis of the winners of the 2010 Nobel Prize for Chemistry. In early October, the Prize was awarded to Richard F. Heck, formerly of the University of Delaware; Ei-ichi Negishi, affiliated with Purdue University; and Akira Suzuki of Hokkaido University for their seminal contributions to “palladium-catalyzed cross couplings in organic synthesis”. The 10 million Swedish kronor (approximately $1.5 million) award will be split among the three recipients. Previous to the groundbreaking work of this year’s winners, the synthesis of stable carbon⫺carbon bonds had been a particularly challenging task. In the early 1900s, the French chemist Victor Grignard devised a method for generating carbon⫺carbon bonds using magnesium to couple ketones and alkyl halides. For the development of this method, he won the 1912 Nobel Prize in Chemistry. This technique had its flaws, however, not the least of which was the unwanted byproducts generated in the process. Heck developed a novel chemical reaction that used palladium to bring carbon atoms of arylmercury compounds and olefins in proximity of each other and facilitate bonding under relatively mild conditions. This work was published in 1968 with Heck as the sole author in seven back-to-back articles in the Journal of the American Chemical Society (1, 2). A drawback to this protocol was that it worked most efficiently with toxic mercury-substituted aromatic rings. In 1971, Tsutomu Mizoroki from the Tokyo Institute of Technology published important work in which he described the nontoxic coupling of halide-substituted aromatic rings with alkenes using palladium as a catalyst (3). As a result, over the past 40 years the nomenclature of this reaction has been a debated point (“Heck reaction” or “Mizoroki⫺Heck reaction”?) among chemists (4). Unfortunately, in 1980, Mizoroki succumbed to pancreatic cancer before he could be honored with a Nobel Prize. Negishi, a Japanese chemist affiliated with Purdue University, was instrumental in further developing this palladium-based coupling method by efficiently producing unsymmetrical biaryls. In 1977, he developed the “Negishi coupling reaction”, which introduced organozinc compounds to a nickel- or palladium-catalyzed coupling reaction. Two years later, Dr. Akira Suzuki, from Sapporo, Japan described the palladium-catalyzed cross coupling between organoboronic acid and halides, known as the “Suzuki coupling reaction”. Through the pivotal work of these three distinguished Nobel laureates, chemists the world over can now more easily synthesize functional molecules around a stable carbon backbone, producing commercially viable products; it is estimated that 25% of all chemical reactions in the pharmaceutical industry utilize these methods. According to Nobel Prize Committee member Claes Gustafsson, palladium-catalyzed coupling reactions are being used to develop new antibiotics against resistant bacteria and are integral in the produc-
10.1021/cb100326r Published online November 19, 2010 © 2010 by American Chemical Society
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Editor’s
LETTER tion of widespread, commercially available pharmaceuticals such as the anti-inflammatory drug naproxen, the active compound in Aleve (5). We congratulate Heck, Negishi, and Suzuki for their pioneering work and for laying the foundation of an ultimate goal of chemistry: the ability to synthesize any organic compound of our choosing.
Jitesh Soares Managing Editor, ACS Chemical Biology REFERENCES 1. Heck, R. F. (1968) Acylation, methylation, and carboxyalkylation of olefins by Group VIII metal derivatives, J. Am. Chem. Soc. 90, 5518–5526. 2. Heck, R. F. (1968) The arylation of allylic alcohols with organopalladium compounds. A new synthesis of 3-aryl aldehydes and ketones, J. Am. Chem. Soc. 90, 5526–5531. 3. Mizoroki, T., Mori, K., and Ozaki, A. (1971) Arylation of olefin with aryl iodine catalyzed by palladium, Bull. Chem. Soc. Jpn. 44, 581. 4. Drahl, C. (2010) In names, history and legacy, Chem. Eng. News 88, 31–33. 5. Ritter, K., and Rising, M. Trio Wins Chemistry Nobel for Key Chemical Tool. http://www.forbes.com/feeds/ap/2010/ 10/06/science-sci-nobel-chemistry_7990348.html (accessed 10/09/10).
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