The Nobel Prize in Chemistry 2001
William S. Knowles, Ryoji Noyori, K. Barry Sharpless
I was born on September 3, 1938 in a suburb of Kobe (now Ashiya), Japan, the first son of Kaneki and Suzuko Noyori. Our family moved to Kobe soon afterwards. I grew up with two younger brothers and a sister in a pleasant city blessed by beautiful natural surroundings. Except for a short period at the end of World War II, I attended an elementary school affiliated to Kobe University from ages six to twelve, and then moved on to Nada Middle and High School from ages twelve to eighteen. I enjoyed many out-door activities in my youth.
My father, Kaneki, was a gifted research director of a chemical company, and his profession strongly influenced the path of my life. At home, we were surrounded by his scientific journals and books and various samples of plastics and synthetic fibers, and were frequently asked to test the quality of products which were under development for commercialization. When I entered middle school, my father took me to a public conference, the topic of which was "nylon". The lecturer explained proudly that this new fiber could be synthesized from coal, air, and water (the then famous catchphrase of DuPont company). Although I knew nothing about industrial technology, I was deeply impressed by the power of chemistry. Chemistry can create important things from almost nothing! The event had an enormous impact on this 12-year-old schoolboy, because it was in 1951, shortly after World War II when Japan was so poor. We were very hungry. It was at this point that it became my dream to be a leading chemist to contribute to the society by inventing beneficial products.
My appetite for chemistry was further wetted through class work led by enthusiastic teachers in middle/high school including Dr. Kazuo Nakamoto (then Osaka University and afterward Illinois Institute of Technology and Marquette University) who gave me my first chemistry lesson. I also liked other sciences and mathematics. Together with regular schoolwork, "judo" (one of Japan's traditional sports) was a major passion at this time. It was very popular amongst us because Nada School and Kodokan Judo School were founded by the same family. I highly appreciate the educational efforts of many schoolteachers as well as the warm friendship of classmates in those days, which strongly influenced the formation of my personal character.
In 1957, at the age of 18, I entered Kyoto University, which was known to be the most active institution in the research of polymer chemistry. Incidentally, this was the year when the USSR launched into space for the first time an artificial satellite, the Sputnik, thereby demonstrating the power of sciencebased technology. I recall that this success substantially shocked young science students in Japan. After three years, I started to study organic chemistry, rather than polymer chemistry, under the guidance of Professor Keiiti Sisido. The laboratory environment was very hospitable and I obtained my Bachelor degree in 1961. Upon completion of my Master's degree in 1963, I was immediately appointed Instructor of Professor Hitosi Nozaki's laboratories at Kyoto University and, in 1967, received my doctorate (DEng). My career path, that is the appointment to Instructor without a doctorate, is a little unusual but this is partly due to the difference in Japanese and Western education/teaching systems. Professor Nozaki strongly encouraged us to pursue new, original chemistry rather than tracing traditional subjects, while I served as a leader of his subgroup working on flourishing physical organic chemistry. It was under such conditions that in 1966 we discovered an interesting asymmetric catalysis that later became a life-long interest. This finding emerged during the course of an investigation of the transition metal effects in carbene reactions. Reaction of styrene and ethyl diazoacetate in the presence of a small amount of a chiral Schiff base-Cu(II) complex gave optically active cyclopropane derivatives, albeit with <10 % ee. Although the enantioselectivity was not synthetically meaningful, this was probably the first example of asymmetric catalysis using structurally well-defined organometallic molecular complexes. In the early 1960s, homogeneous catalysis (typically Reppe chemistry) was already well known, however, the notion of "molecular catalysis" that utilizes the structural and electronic characteristics of molecules more positively, was not clearly documented. This discovery opened my research perspective. In any event, I intended first to expand my scientific background under the supervision of an eminent chemist abroad, and Professor E.J. Corey at Harvard kindly agreed to accommodate me in his laboratories as a postdoctoral fellow. This plan, however, was postponed for reasons outlined below.
The situation changed drastically in the fall of 1967, when I received a totally unexpected offer from Nagoya University. I was asked to chair a newly created organic chemistry laboratory. This invitation surprised me. I was a mere 29-year-old Instructor at Kyoto enjoying daily research work with some young students. Nothing had prepared me to be a Professor at a major national university. Being too young and inexperienced to be a Full Professor, I was first appointed Associate Professor of Chemistry. In February, 1968, when I launched my own research group, Professor Yoshimasa Hirata, a senior faculty known for his outstanding accomplishments in natural products of organic chemistry, asked me to create a new stream of organic chemistry at Nagoya, different from his own field, thereby making the Chemistry Department more visible. I immediately decided to focus on organic synthesis using organometallic chemistry, which then comprised a branch of inorganic chemistry. Although not many researchers were aware of the high utility in organic synthesis, I was intuitively confident of the bright future of this scientific field. Professor Hirata consistently helped me in many aspects during his time at Nagoya University.
In 1969, as planned earlier, I went to Harvard. I was amazed by the enormous difference in the standard of living and science between the US and my mother country. Professor Corey was then already a leading organic chemist and I learned much from him. In addition, I became acquainted with many promising students and postdoctoral fellows including K. Barry Sharpless who was working with Professor Konrad Bloch. Later many of these reliable friends, together with their scientific relatives, grew to become eminent researchers in the scientific community and helped me in many ways. Synthesis of prostaglandins (PGs) was my research theme in the Corey group. After completing several works, I was asked to selectively hydrogenate a PGF2a derivative that has two C = C bonds to a PGF1a compound possessing a single C = C bond. This was the start of my three-decade-long work on hydrogenation. My interest in homogenous hydrogenation was enhanced by reading almost all available literature on this very new topic and also through personal interaction with Assistant Professor John A. Osborn, who had joined Harvard Chemistry Department from Geoffrey Wilkinson's laboratory at Imperial College, London. Osborn, an authority of Rh-catalyzed homogeneous hydrogenation, taught me many aspects of organometallic chemistry. It was in 1968, when W.S. Knowles and L. Horner reported independently the first homogeneous asymmetric hydrogenation using chiral phosphine-Rh catalyts, albeit in low optical yields. The fruitful Harvard experience, coupled with our earlier asymmetric cyclopropanation in 1966, led to my life-long research on asymmetric hydrogenation.
After returning to Nagoya in 1970, I began to study organic synthesis and homogeneous catalysis via organometallic chemistry, while in August 1972, at the age of 33, I was promoted to Full Professor. In the hope of development of efficient asymmetric hydrogenation and other reactions, we became interested in BINAP [2,2'-bis(diphenylphosphino)-1,1'-binaphthyl], a novel C2 chiral diphosphine possessing a beautiful molecular shape. Synthesis of the optically pure diphosphine was unexpectedly difficult. It was in 1974, that I started stereospecific synthesis from optically pure 2,2'-diamino-1,1'-binaphthyl with my long-term collaborator, the late Professor Hidemasa Takaya, who was with me at Nagoya and afterwards moved to the Institute of Molecular Science and Kyoto University. After two years, we managed to obtain optically active BINAP, however, the result was disappointingly irreproducible. In 1978, we reached a reliable method for resolution of racemic BINAP with a chiral amine-Pd complex. Unfortunately, the results of BINAP-Rh(I) catalyzed asymmetric hydrogenation of dehydro amino acids were highly variable depending on the reaction conditions. Eventually, in 1980 after a six-year endeavour, thanks to the unswerving efforts of my young colleagues and students, we were able to publish our first work on asymmetric synthesis of amino acids via this BINAP chemistry.
The success in our asymmetric hydrogenation largely relies on the invention of BINAP and the use of Ru element, which behaves differently from conventional Rh. A major breakthrough in asymmetric hydrogenation came in 1986, when we developed BINAP-Ru(II) dicarboxylate complexes that enjoy a much greater scope of olefinic substrates. Furthermore, in 1987-1988, 179 we developed a versatile general asymmetric hydrogenation of functionalized ketones with BINAP-Ru(II) dihalide complexes. The scope of this method is far reaching. These asymmetric hydrogenation methods allow for the synthesis of a wide array of terpenes, vitamins, b-lactam antibiotics, a- and b-amino acids, alkaloids, prostaglandins, and other compounds of biological and physiological interest. BINAP chemistry has been applied to the large-scale production of the synthetic intermediates of antibiotic carbapenems (Takasago International Co.) and levofloxacin, a quinolone antibacterial agent (Takasago International Co./Daiichi Pharmaceutical Co.). The efficiency of BINAP chemistry rivals or in certain cases even exceeds that of enzymes. In addition, a team of the Noyori Molecular Catalysis Project (ERATO, 1991-1996) discovered the catalysts of type RuCl2(diphosphine)(diamine) leading to another major breakthrough in hydrogenation. The reaction of unsaturated ketones occurs preferentially the C = O function leaving the olefinic linkage intact. The combined use of the BINAP ligand and a chiral diamine effects asymmetric hydrogenation of a range of aromatic, hetero-aromatic, and olefinic ketones. The reaction is very rapid, productive and stereoselective, providing the most practical method for converting simple ketones to chiral secondary alcohols.
BINAP-Rh(I) complexes are useful for asymmetric isomerization of allylic amines to enamines of high enantiomeric purity. In the early 1980s, a fruitful academic/industry collaboration was made between the groups at Osaka University (S. Otsuka and H. Tani), Nagoya University, Institute of Molecular Science (H. Takaya), Shizuoka University (J. Tanaka and K. Takabe), and Takasago International Co., realizing the industrial production of (-)-menthol and other optically active terpenes.
In 1995-1996, we invented a range of Ru(II) catalysts modified with a chiral b-amino alcohol or 1,2-diamine derivative that effects asymmetric transfer hydrogenation of ketones and imines using 2-propanol or formic acid as hydrogen donors. More recently, the reaction has proven to proceed via a nonclassical metal - ligand bifunctional mechanism. My interest in asymmetric chemistry is broad. In 1986, we found a highly enantioselecive addition of dialkylzincs to aldehydes using a small quantity of a camphor-derived chiral amino alcohol, where the alkylation products with high enantiomeric excesses are accessible with a partially resolved chiral ancillary. We could fully elucidate the origin of this striking chiral amplification phenomenon at the molecular structure level. My stay at Harvard in 1969-1970 spurred me to develop an efficient way to synthesize prostaglandins (PGs). In this connection, a series of selective synthetic methods was explored in our laboratories. Our binaphthol-modified lithium aluminum hydride reagent (1979) was applied to the commercial Corey PG synthesis (Ono Pharmaceutical Co.). Furthermore, we realized the long-sought three-component PG synthesis in 1985, which now plays an important role in biochemical and physiological studies of PGs.
Chemical synthesis provides a logical basis for molecular science and related technologies which require a high degree of structural precision. I have 180 tried to select general and fundamental research subjects in this important field. A clear-cut solution to a long-persistent problem, when accomplished, often results in an enormous scientific or technological impact. Asymmetric hydrogenation is a typical example. BINAP chemistry is now utilized worldwide in research laboratories and also at the industrial level. In fact, the selective synthesis of single enantiomers using well-designed chiral molecular catalysts has now become common practice. This fascinating field is still growing rapidly, and recent advances have dramatically changed the way of chemical synthesis, opening tremendous potential for molecular technologies.
Our broad research activity goes beyond asymmetric synthesis. In 1994, we discovered the remarkable utility of supercritical carbon dioxide as a medium for homogeneous catalysis. Thus Ru-catalyzed hydrogenation produces formic acid, methyl formate, and dimethylformamide with an extremely high turnover number. More recently, we devised practical, environmentally sound methods for olefin epoxidation and alcohol oxidation using aqueous H2O2, whose utility is highlighted by the direct conversion of cyclohexene to adipic acid (1996-1998). The stereospecific living polymerization of phenylacetylenes was achieved by using a structurally defined tetracoordinate Rh complex (1994). We also developed an efficient synthesis of solid-anchored DNA oligomers using organopalladium chemistry (1990). In my early days at Nagoya, we invented the iron carbonyl-polybromo ketone reaction which allows the construction of five- and seven-member carbocycles in a 3 + 2 and 3 + 4 manner, respectively. In the late 1970s, we exercised initiative in the catalytic use of organosilicon compounds for organic synthesis.
Organometallic chemistry is a scientific space leading to an enormous technical impact and even more general social benefits. I am very pleased to be involved in contributing to the progress of this significant scientific realm. The above described scientific accomplishments are not my own, but the credit in fact belongs to my research family at Nagoya University and many collaborators at other institutions. My initial ideas in solving problems were not always appropriate and, sometimes even nonsensical. However, my serendipitous collaborators incubated such research themes through careful experiments and much deliberation, and eventually reached new chemical concepts and useful methodologies. Their intellect, sense, and skills are highly appreciated. In addition, through my frequent traveling abroad as a visiting professor or invited lecturer at research institutions and conferences, I have met many superb colleagues from the international scientific community. Their encouragement as well as the exposure to different cultures and environments have deeply affected my way of thinking. Furthermore, for over three decades, my scientific work has been supported generously and consistently by the Ministry of Education, Culture, Sports, Science and Technology of Japan as well as the Research Development Corporation of Japan, various private foundations, and numerous industrial companies.
My activities are not limited to education and research. I have served on the editorial boards of some thirty international journals including the editorship of Advanced Synthesis & Catalysis (Wiley/VCH) which emphasizes the "practical elegance" of chemical synthesis. Furthermore, I have been involved in much administrative work, for example, as Science Advisor (1992-1996) and Member of the Scientific Council (1996-present) of the Ministry of Education, Culture, Sports, Science and Technology; Dean of the Graduate School of Science at Nagoya University (1997-1999); and President of the Society of Synthetic Organic Chemistry, Japan (1997-1999). Such official duties significantly hamper my research activity but are unavoidable for a senior scientist.
In 1972, I married Hiroko Oshima (a daughter of a Professor of Medicine at Tokyo University) who was studying the immunology of cancer at a research institute in Tokyo. Since then, she has played the most important part in our private life at Nagoya. We have two children. Our first son, Eiji (born in 1973), is an active staff writer of a newspaper company, and our second son, Koji (born in 1978), studies painting at an art university in Tokyo.
|Kyoto University: Instructor, 1963-1968.|
|Nagoya University: Associate Professor, 1968-1972. Professor, 1972-present. Director Chemical Instrument Center, 1979-1991. Dean, Graduate School of Science, 1997-1999. Director, Research Center for Materials Science, 2000-present.|
|Kyushu University: Professor (adjunct), 1993-1996.|
|Ministry of Education, Science, Sports and Culture: Science Advisor, 1992- 1996. Member of Scientific Council, 1996-2001.|
|Ministry of Education, Culture, Sports, Science and Technology: Member of Scientific Council, 2001-present.|
|Japan Society for the Promotion of Science: Committee Chairman, Research for the Future Program on "Advanced Processes", 1996-present. Science Advisor, 2001-present.|
|The Research Development Corporation of Japan: Director of the ERATO Molecular Catalysis Project, 1991-1996.|
|The Society of Synthetic Organic Chemistry, Japan: Vice President, 1994- 1996. President, 1997-1999.|
|The Chemical Society of Japan: President-Elect, 2001.|
|Technische Universität München, Germany, 1995.|
|Université de Rennes 1, France, 2000.|
|Shanghai Institute of Organic Chemistry, China, 2001.|
|Fellowships and Memberships|
|Fellow, American Association for the Advancement of Science, 1996.|
|Honorary Member, Chemical Society of Japan, 1998.|
|Honorary Fellow, Royal Society of Chemistry, UK, 2000.|
|Foreign Honorary Member, American Academy of Arts and Sciences, 2001.|
|Honorary Member, European Academy of Sciences and Arts, 2001.|
|The Chemical Society of Japan Award for Young Chemists, 1972.|
|The Matsunaga Prize (Matsunaga Memorial Foundation, Japan), 1978.|
|The Chunichi Cultural Prize (Chunichi Newspaper Co., Japan), 1982.|
|The Chemical Society of Japan Award, 1985.|
|The Naito Foundation Research Prize (Naito Science Foundation, Japan), 1988.|
|The Fluka Prize, Reagent of the Year (Fluka Chemie AG, Switzerland), 1989.|
|The Centenary Medal (The Royal Chemical Society, UK), 1990.|
|The Toray Science & Technology Prize (Toray Science Foundation, Japan), 1990.|
|The Merck-Schuchardt Chair (BOSS Symposium, Belgium), 1990.|
|The J. G. Kirkwood Award (Yale University, USA), 1991.|
|The Asahi Prize (Asahi Culture Foundation, Japan), 1992.|
|Tetrahedron Prize for Creativity in Organic Chemistry (Pergamon Press, UK), 1993.|
|The Keimei Life Science Prize (Keimei Foundation, Japan), 1994.|
|The Japan Academy Prize, 1995.|
|The Arthur C. Cope Scholar Award (American Chemical Society), 1996.|
|Bonn Chemistry Award (University of Bonn and Pinguin Foundation, Germany), 1996.|
|The Arthur C. Cope Award (American Chemical Society), 1997.|
|The Chirality Medal (International Symposium on Chiral Discrimination), 1997.|
|The George Kenner Award (University of Liverpool, UK), 1997.|
|Person of Cultural Merit (Japanese Government), 1998.|
|The King Faisal International Prize for Science (King Faisal Foundation, Saudi Arabia), 1999.|
|The Cliff S. Hamilton Award (University of Nebraska, USA), 1999.|
|ISI Citation Laureate Award (ISI/Thomson Scientific Inc., USA/Japan), 2000.|
|The Order of Culture (Japanese Emperor/Government), 2000.|
|The Special Award (The Society of Synthetic Organic Chemistry, Japan), 2001.|
|The Wolf Prize in Chemistry (Wolf Foundation, Israel), 2001.|
|The Roger Adams Award in Organic Chemistry (American Chemical Society), 2001.|
|The Nobel Prize in Chemistry (Royal Swedish Academy of Sciences), 2001.|
|Over 400 publications in scientific journals.|
|Monograph: "Asymmetric Catalysis in Organic Synthesis." R. Noyori, John Wiley & Sons, New York, 1994.|
|Asymmetric Induction in Carbenoid Reaction by Means of a Dissymmetric Copper Chelate. H. Nozaki, S. Moriuti, H. Takaya, and R. Noyori, Tetrahedron Lett., 5239 (1966).|
|Organic Syntheses via the Polybromo Ketone-Iron Carbonyl Reaction. R. Noyori, Acc. Chem. Res., 12, 61 (1979).|
|Synthesis of 2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), an Atropisomeric Chiral Bis(triaryl)phosphine, and Its Use in the Rhodium(I)- Catalyzed Asymmetric Hydrogenation of a-(Acylamino)acrylic Acids. A. Miyashita, A. Yasuda, H. Takaya, K. Toriumi, T. Ito, T. Souchi, and R. Noyori, J. Am. Chem. Soc., 102, 7932 (1980).|
|Prostaglandin Syntheses by Three-Component Coupling. R. Noyori and M. Suzuki, Angew. Chem., Int. Ed. Engl., 23, 847 (1984).|
|The Allylic Protection Method in Solid-Phase Oligonucleotide Synthesis. An Efficient Preparation of Solid-Anchored DNA Oligomers. Y. Hayakawa, S. Wakabayashi, H. Kato, and R. Noyori, J. Am. Chem. Soc., 112, 1691 (1990).|
|An Organometallic Way to Prostaglandins: The Three-Component Coupling Synthesis. R. Noyori and M. Suzuki, Chemtracts-Org. Chem., 3, 173 (1990).|
|Chiral Metal Complexes as Discriminating Molecular Catalysts. R. Noyori, Science, 248, 1194 (1990).|
|BINAP: An Efficient Chiral Element for Asymmetric Catalysis. R. Noyori and H. Takaya, Acc. Chem. Res., 23, 345 (1990).|
|Enantioselective Addition of Organometallic Reagents to Carbonyl Compounds: Chirality Transfer, Multiplication, and Amplification. R. Noyori and M. Kitamura, Angew. Chem., Int. Ed. Engl., 30, 49 (1991).|
|Stereoselective Organic Synthesis via Dynamic Kinetic Resolution. R. Noyori, M. Tokunaga, and M. Kitamura, Bull. Chem. Soc. Jpn., 68, 36 (1995).|
|Homogeneous Catalysis in Supercritical Fluids. P. G. Jessop, T. Ikariya, and R. Noyori, Science, 269, 1065 (1995).|
|Asymmetric Hydrogenation. R. Noyori, Acta Chem. Scand., 50, 380 (1996).|
|The Catalyst Precursor, Catalyst, and Intermediate in the RuII-Promoted 184 Asymmetric Hydrogen Transfer between Alcohols and Ketones. K.-J. Haack, S. Hashiguchi, A. Fujii, T. Ikariya, and R. Noyori, Angew. Chem., Int. Ed. Engl., 36, 285 (1997).|
|Asymmetric Transfer Hydrogenation Catalyzed by Chiral Ruthenium Complexes. R. Noyori and S. Hashiguchi, Acc. Chem. Res., 30, 97 (1997).|
|A "Green" Route to Adipic Acid: Direct Oxidation of Cyclohexenes with 30% Hydrogen Peroxide. K. Sato, M. Aoki, and R. Noyori, Science, 281, 1646 (1998).|
|Asymmetric Catalysis by Architectural and Functional Molecular Engineering: Practical Chemo- and Stereoselective Hydrogenation of Ketones. R. Noyori and T. Ohkuma, Angew. Chem., Int. Ed., 40, 40 (2001).|
|Self and Nonself Recognition of Chiral Catalysts: The Origin of Nonlinear Effects in the Amino-Alcohol Catalyzed Asymmetric Addition of Diorganozincs to Aldehydes. R. Noyori, S. Suga, H. Oka, and M. Kitamura, Chem. Rec., 1, 85 (2001).|
|Metal-Ligand Bifunctional Catalysis: A Nonclassical Mechanism for Asymmetric Hydrogen Transfer between Alcohols and Carbonyl Compounds. R. Noyori, M. Yamakawa, and S. Hashiguchi, J. Org. Chem., 66 7931, (2001).|
From Les Prix Nobel. The Nobel Prizes 2001, Editor Tore Frängsmyr, [Nobel Foundation], Stockholm, 2002
This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/Nobel Lectures. The information is sometimes updated with an addendum submitted by the Laureate.
Copyright © The Nobel Foundation 2001
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