Ryoji Noyori

A research profile of Professor Noyori from Nagoya University in Japan, who shared the 2001 Nobel Prize in Chemistry with William Knowles and Barry Sharpless “for their work on chirally catalysed reactions”.

Timeline

1961: Kyoto University, Bachelor, with Professor K. Sisido

1963: Kyoto University, Master, with Professor K. Sisido

1963: Kyoto University, Instructor with Professor H. Nozaki

1967: Kyoto University, Ph.D. (Dr. of Eng.), with Professor H. Nozaki

1968: Nagoya University, Associate Professor

1969–1970: Harvard University, Postdoctoral Fellow with Professor E. J. Corey

1972 to present: Nagoya University, Professor

1979–1991: Nagoya University, Director of Chemical Instrument Center

1991–1996: Research Development Corporation of Japan, Director of ERATO Noyori

Molecular Catalysis Project

1992–1996: Ministry of Education, Science and Culture, Science Advisor

1993–1996: Kyushu University, Adjunct Professor

1996–2003: Ministry of Education, Science and Culture, Member of Scientific Council

1997–1999: Nagoya University, Dean of Graduate School of Science

1997–1999: The Society of Synthetic Organic Chemistry, Japan, President

2000 to present: Nagoya University, Director of Research Center of Materials Science

2001 to present: The Japan Society for the Promotion of Science, Science Advisor

2002–2003: The Chemical Society of Japan, President

2002 to present: Nagoya University, Director of Institute for Advanced Research

2002 to present: Meijo University, Guest Professor

Awards

Major Awards: Chemical Society of Japan Award (1985); Asahi Prize (1992); Tetrahedron Prize (1993); Japan Academy Prize (1995); Arthur C. Cope Award (1997); Person of Cultural Merit (1998); King Faisal International Prize (1999); The Order of Culture (2000); Wolf Prize in Chemistry (2001); Roger Adams Award (2001); Nobel Prize in Chemistry (2001).

Honorary Degrees: Technische Universität München (1995); University of Rennes (2000); University of Bologna (2002); University of Alicante (2003); Uppsala University (2003); University of Ottawa (2003); University of Chicago (2003).

Honorary Professorships: Shanghai Institute of Organic Chemistry (2001); Hong Kong Polytechnic University (2002); South China University of Technology (2002).

Academies: Pontifical Academy of Sciences (2002); Japan Academy (2002); National Academy of Sciences, Washington, DC (2003).

Honorary Memberships: American Association for the Advancement of Science (1996); Chemical Society of Japan (1998); Royal Society of Chemistry, London (2000); American Academy of Arts and Sciences (2001); European Academy of Sciences and Arts, Vienna–Salzburg (2001); Society of Synthetic Organic Chemistry, Japan (2002); Pharmaceutical Society of Japan (2002); Kinki Chemical Society (2002); European Academy of Sciences, Brussels (2002).

Ryoji Noyori was born on September 3, 1938, in Kobe, Japan. He now lives in Nisshin City, a suburb of Nagoya, with his wife, Hiroko, and their older son, Eiji, who is working as a staff writer for a newspaper company. Their younger son, Koji, studies painting at an art university in Tokyo. Currently, Noyori conducts research and teaches at Nagoya University, but he is deeply involved in public and administrative works in Tokyo. He very frequently travels back and forth between Nagoya and Tokyo and also gives many lectures worldwide. The official duties and administrative responsibilities associated with being a senior scholar currently demand much of his time, which is otherwise dedicated to advancing the field of synthetic chemistry.

Research

Chemistry is not merely a science of making observations in order to better understand Nature. It is creative and productive. We chemists are proud of our ability to create high values from almost nothing on the basis of accumulated scientific knowledge. Our field of study has greatly enhanced the quality of life worldwide by providing an impressive range of useful man-made substances and materials. In order to realize the sustainable development of the global society in this new millennium, advanced chemical processes must be economical, safe, environmentally benign, and resource- and energy-saving. Thus new catalytic systems effecting ‘perfect chemical reactions’ will be in increased demand; such reactions would give only the desired products, with 100% selectivity and 100% yield, and without unwanted waste products. Every reaction of a multi-step synthesis should proceed with a high atom-economy, and the overall synthesis needs to be accomplished with a low E (ecological) factor. Long before Green Chemistry received proper appreciation, the Noyori research group had already consistently focused on molecular catalysis and, consequently, contributed in many ways to the progress of modern chemistry directed toward this goal.

Hydrogenation is a core technology in the field of chemical synthesis. When it gives the desired selectivity, this catalytic approach is much more beneficial than conventional stoichiometric metal hydride chemistry. For quite some time, we have engaged in the development of efficient asymmetric hydrogenation, where the designing of efficient chiral catalysts and the selection of suitable reaction conditions are the key issues. In 1980, we devised a new atropisomeric chiral diphosphine referred to as BINAP. In particular, our discovery of BINAP–Ru(II) complex catalysts led to the asymmetric hydrogenation of functionalized olefins and ketones of high generality. Furthermore, our invention of the catalysts of the type RuCl₂(diphosphine)(1,2-diamine) provided a major breakthrough in stereoselective organic synthesis. This method enabled the asymmetric hydrogenation of a wide range of aromatic, hetero-aromatic, and olefinic ketones. This reaction is very rapid, productive, and stereoselective, and it provides the most practical means of converting simple ketones to desired chiral secondary alcohols. Furthermore, we invented a range of η⁶-arene–Ru(II) catalysts modified with a chiral β-amino alcohol or a 1,2-diamine derivative that enabled the asymmetric transfer hydrogenation of ketones and imines using 2-propanol or formic acid as hydrogen donors. These processes have been applied in the synthesis of numerous chiral compounds including terpenes, vitamins, β-lactam antibiotics, α- and β-amino acids, alkaloids, prostaglandins, and other compounds of biological interest. Further technical refinements have led to the large-scale industrial production of the synthetic intermediates of antibiotic carbapenems and an antibacterial quinolone, among other pharmaceuticals. The efficiency of the asymmetric catalysts discovered by the Noyori group rivals or, in certain cases, exceeds that of enzymes.

The BINAP–Rh(I) complexes were found to catalyze asymmetric isomerization of allylic amines to enamines of high enantiomeric purity. The reaction using geranyldiethylamine, giving (R)-citronellal diethylenamine, currently plays a key role in the industrial production of (−)-menthol and other optically active terpenes, producing a total of 2000 tons per year. This process was accomplished at Takasago International Co. together with the research groups of S. Otsuka and H. Takaya.

Recent progress in asymmetric synthesis has revolutionized the approach to chemical synthesis. Efficient asymmetric catalysis now generally utilizes chiral organometallic molecular catalysts that consist of a metallic element and a beneficially shaped chiral organic ligand(s). This widely practised catalytic principle dates back to our discovery in 1966 of the asymmetric cyclopropanation of styrene with diazoacetates in the presence of a small amount of a chiral Schiff base–Cu complex, although only a low level of enantioselectivity was achieved with that earlier catalyst.

Organic reactions are performed largely in liquid organic solvents. For both scientific and environmental reasons, the development of new reaction media is now becoming extremely important. We demonstrated for the first time the remarkable utility of supercritical CO₂ as a ‘green’ medium for homogeneous catalysis by accomplishing the hydrogenation of supercritical CO₂ catalyzed by RuH₂[P(CH₃)₃]₄ or RuCl₂[P(CH₃)₃]₄. Hydrogenation in the presence of triethylamine occurs very rapidly, whereas the addition of methanol results in thermal esterification, producing methyl formate in a high yield. Hydrogenation in the presence of dimethylamine, giving DMF, proceeds with unprecedented efficiency. This finding has served as the basis for further studies investigating the utility of supercritical fluids in other catalytic reactions.

Although oxidation is a fundamental means of converting petroleum-based materials to useful chemicals with a higher oxidation state, this remains an extremely problematic process from an environmental point of view. Many textbook oxidation methods are unacceptable for practical synthesis. H₂O₂, viewed as an adduct of an O atom and an H₂O molecule, is a ‘green’ and relatively cheap [<0.7 US dollar kg⁻¹ (100% H₂O₂)] oxidant that is attractive for liquid-phase reactions. Recently, we found that, when coupled with a tungstate complex and a quaternary ammonium hydrogensulfate as an acidic phase-transfer catalyst, aqueous H₂O₂ oxidizes alcohols, olefins, and sulfides under organic solvent- and halide-free conditions in an economically, technically, and environmentally satisfying manner. The turnover numbers of the biphasic oxidation of secondary alcohols to ketones were two orders of magnitude higher than any previously reported. With this approach, straight-chain primary alcohols can be directly oxidized to carboxylic acids. In addition, this method allows the epoxidation of various olefins, including terminal olefins which are otherwise cumbersome substrates to epoxidize. We now strongly recommend that the current practices using toxic stoichiometric oxidants be replaced by these more efficient catalytic processes. The H₂O₂ oxidation method was successfully applied to achieve the direct conversion of cyclohexene to analytically pure, colorless adipic acid. The current industrial production of adipic acid employs the nitric acid oxidation of cyclohexanol or a cyclohexanol–cyclohexanone mixture. In contrast, this newly developed ‘green route’ avoids the emission of N₂O, which is a known contributor to global warming and ozone depletion.

Our endeavors are not limited to Green Chemistry. Other major accomplishments in the field of asymmetric synthesis have included the invention of a chirally modified lithium aluminium hydride reagent and its application to prostaglandin synthesis; the establishment of a three-component asymmetric synthesis of prostaglandins; the discovery of a highly enantioselective addition of dialkylzincs to aldehydes catalyzed by chiral amino alcohols and the elucidation of the molecular mechanism of the chirality amplification (non-linear effects); and the demonstration of the general utility of dynamic kinetic resolution in asymmetric catalysis. The iron carbonyl–polybromo ketone reaction, discovered during my early days in Nagoya, enabled the construction of five- and seven-membered carbocycles in a [3 + 2] and [3 + 4] manner, respectively. My research group exercised initiative in the catalytic use of organosilicon compounds for organic synthesis. In addition, we explored a series of synthetic methodologies using organocopper, -tin, and -zinc reagents for selective carbon–carbon bond forming reactions. The combined use of these reactions with our asymmetric reduction of ketones has resulted in the long-sought convergent synthesis of prostaglandins. We also achieved the first truly efficient synthesis of solid-anchored DNA oligomers using organopalladium chemistry. Overall, the applications of our original and versatile approaches have allowed us and many other scientists to achieve the truly efficient synthesis of numerous organic molecules of theoretical and practical importance.

Conclusion

Chemical synthesis is crucial for the future of mankind because this significant realm provides a logical and technical basis for the natural sciences and technologies. Thus, chemists have an immense responsibility to solve a wide range of current, or even unforeseen, social and global problems associated with health, synthetic materials, food, energy, the environment, and many other aspects of life. Theoretically, we can synthesize an infinite variety of compounds in any quantity. However, the practical synthesis is currently limited to the production of substances in small volumes and to those with a very high value. Synthetic efficiency is in reality limited only by scientific principles and the boundary conditions of our planet, rather than by economical and biological factors. Chemists are thus encouraged to develop truly efficient processes at all costs, and the key phrase in this context should be ‘Practical Elegance’. Without Green Chemistry, chemical manufacturing will be unable to survive into the 22nd century. However, these are not matters of clear-cut scientific or technical expertise, but rather these issues are serious, complex social issues. In addition to our efforts as scientists, public understanding and agreement, as well as worldwide cooperation, are crucial for the realization of sustainable societies. Most importantly, such endeavors not only protect our environment but also greatly contribute to an improvement in the quality of life for future generations. If we can dream today, we can live tomorrow.

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