The Ryu Research Group, Department of Chemistry, Graduate School of Science, Osaka Prefecture University

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New Reactions, New Media, New Devices


Within our Laboratory, the Projects focus on the invention of new synthetic methodologies, which could be potentially useful in organic synthesis. The utilization of potentially cheap feedstock, like CO, alkenes, and alkynes, is always within our focus. Furthermore special emphasis is placed on both unique free-radical and organo-transition metal species to achieve useful transformations. Present interests also include “green” synthetic reactions and processes. The latter use new reaction media such as fluorous solvents and ionic liquids. Thus the synthetic procedures can be conducted without the use of harmful organic solvents. Another current research program in our groups is the application of microreactors for the execution of synthetic reactions, which would be generation of chemical tools, replacing a traditional glass-made batch reactors. In this way, organic synthesis and processes would be modernized to accommodate to the criteria of green chemistry.

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Utilization of Carbon Monoxide for Organic Synthesis

Carbon monoxide is a cheap feedstock obtained from coal and steam and we aim to explore new synthetic methodologies for the incorporation of carbon monoxide into organic molecules. We have successfully prepared a variety of compounds where carbon monoxide has been incorporated as a carbonyl function, especially our attention has been paid to the potential of radical carbonylation reactions.

Syn Gas from Coal and Hot Water

Radical Reactions of Carbon Monoxide

The comparison of the following two reactions developed by us and the Stille group, independently, which synthesize aldehydes from organic halides, CO, and trbutyltin hydride, well feature the characteristics of radical carbonylations. A broad scope of organic halides including aliphatic halides can be used for radical carbonylation.


The following Scheme demonstrates some of our achievements in this area. On the other hand, our procedure requires pressurized conditions, and therefore we are now pursuing atmospheric CO reactions.


Specific examples are show here. Cascade reactions, which can make multi C-C bonds in a consecutive manner, features modern organic free radical chemistry. Recent achievements in this Laboratory include novel carbonylation methods for the synthesis of a-methylene lactams based on nitrogen-philic cyclization of acyl radicals onto imine N-C double bonds. The elucidated transition state is in contrast with that of acyl radical cyclization onto C-C double bond.



Miyazato, H.; Kuriyama, H.; Tojino, M.; Komatsu, M.; Ryu, I. et al. J. Am. Chem. Soc. 2003, 125, 5632
Tojino, M.; Otsuka, N.; Fukuyama, T.; Matubara, H.; Ryu, I. J. Am. Chem. Soc. 2006, 128, 7712. Matsubara, H.; Falzon, C. T.; Ryu, I.; Schiesser, C. H. Org. Biomol. Chem. 2006, 4, 1920.
Schiesser, C. H.; Wille, U.; Matsubara, H.; . Ryu, I. Acc. Chem. Res. 2007, 40, 303.

We aimed at development of cascade reactions. In the following example functionalized 1,5-diketones can be synthesized in one-operation. The reaction can combine four carbon-components. Elucidation of polar character of acyl radicals led us to explore new type of carbonylation reaction leading to acrylic amide synthesis in which ionic reaction favorably participates in radical chain steps as the key.



Selected Reviews on Radical/CO chemistry: I. Ryu, N. Sonoda, D. P. Curran, Chem. Rev. 1996, 96, 177. I. Ryu, N. Sonoda, Angew. Chem. Int. Ed. Engl. 1996, 35, 1050. I. Ryu, Chem. Soc. Rev. 2001, 30. 16. I. Ryu, Chem. Rec. 2002, 2, 249. I. Ryu, H. Matsubara, Y. Uenoyama, Bull. Chem. Soc. Jpn, 2006, 79, 1476. C. H. Schiesser, U. Wille, H. Matsubara, I. Ryu, Acc. Chem. Res. 2007, 40, 303.

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Novel Synthetic Transformations Based on Unique Dianionic Species

A new reaction utilizing cuprate chemistry was discovered within our group: it involves novel organocopper reagents, derived from the ketone α,β-dianions, which undergo a formal formal [3+2]cycloaddition reaction with cyclohexenone, to form keto alcohols in good yields. We accounted for this unusual reaction by proposing a carbocupuration mechanism rather than the well advocated β-copper(III) ketone mechanism.


A new class of ketone dilithio dianions can be generated by vinylogous extenstion of ketone α,β-dianions. Thus, the dianions can be used as a useful platform of ketone frameworks.


Ryu, I.; Nakahira, H.; Ikebe, M.; Sonoda, N.; Yamato, S.; Komatsu, M. J. Am. Chem. Soc., 2000, 122, 1219.
Yamato, S.; Yamamura, G.; Komatsu, M.; Arai, M.; Fukuyama, T.; Ryu, I. Org. Lett. 2005, 7, 2489.
Nakahira, H.; Ikebe, M.; Oku, Y.; Sonoda, N.; Fukuyama, T.; Ryu, I. Tetrahedron, 2005, 61, 3383.

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Metal Hydrides: New Catalytic Transformations

Development of novel catalytic reactions is another research goal in this Laboratory. We have recently found that ruthenium hydride complexes work as an efficient catalyst for novel homo-and cross-coupling reactions of oxygen containing compounds. Such examples include dimerization of unsaturated alcohols and reductive dimerization of unsaturated aldehydes, in which ruthenium hydride complex acts as multi-task catalyst.


T. Doi, T. Fukuyama, S. Minamino, G. Husson, I. Ryu, Chem. Commun. 2006, 1875.


The chemistry involved in the above transformation led us to develop a number of atom-economical reactions, which can convert readily available starting substrates to important carbonylacompounds.


T. Fukuyama, T. Doi, S, Minamino, S, Omura, I. Ryu, Angew. Chem. Int. Ed. 2007, 46, 5559.
S. Omura, T. Fukuyama, J. Horiguchi, Y. Murakami, I. Ryu, J. Am. Chem. Soc. 2008, 130, 14094. S. Omura, T. Fukuyama, Y. Murakami, H. Okamoto, I. Ryu, Chem. Commun., 2009, 6741.
A. Denichoux, T. Fukuyama, T. Doi, J. Horiguchi, I. Ryu, Org, Lett. 2010, 12, 1.

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Green Chemistry and Green Technology


Fluorous Solvents as Reaction Media and Liquid Membrane

Fluorous hybrid solvent, F-626, was found within our group to be a recyclable reaction medium, which can be used as a substitute for DMF, diethyleneglycol, and o-dichlorobenzene for traditional synthetic reactions. Recent work include the use of F-626 for thermally induced Retro-Aldol reactions.


F-626 is a SAFF solvent!

The use of perfluorocarbons as a phase screen provides a Phase-Vanishing Method which can eliminate the need for dropping addition of reagents in exothermic reactions.


Fukuyama, T.; Arai, M.; Matsubara, H.; Ryu, I. J. Org. Chem. 2004, 69, 8105.
Matsubara, H.; Yasuda, S.; Ryu, I. Synlett., 2003, 247.
Ryu, I.; Matsubara, H.; Yasuda, S.; Nakamura, H.; Curran, D. P. J. Am. Chem. Soc. 2002, 124, 12946.
Fukuyama, T.; Kawamoto, T.; Okamura, T.; Denichou, A.; Ryu, I. Synlett. 2010, 2193.
Review: Ryu, I.; Matsubara, H.; Nakamura, H.; Curran, D. P. Chem. Rec. 2008, 8, 351.

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Microflow Synthesis of Organic Molecules by Recyclable Catalytic Reactions Using Ionic Liquids as Catalyst Support

Microchannels having 50 to 300 mm diameter can be used as a reaction space, where highly efficient heat transfer and mass transfer are possible. We have shown that several palladium catalyzed reactions proceed smoothly in a microflow system, using a micromixer with a channel width of 40 mm. One example of this is Sonogashira coupling reactions that have been conducted using a microflow system, providing good yields of the acetylenic compounds with catalyst recycling.


Superior efficiency of the microflow system over the batch version was found for carbonylation reaction conducted in ionic liquids. Thus, we carried out the first model carbonylation reaction between iodobenzene and phenyl acetylene using this microflow setup and we found it intriguing that even with much lower CO pressures, such as 5 atm or 3 atm, only the desired carbonylated product was obtained and no byproduct formation was observed. In a sharp contrast, the carbonylation efficiency was seriously plagued at lower CO pressures (5 or 3 atm) when an autoclave reactor was used, giving dominantly the undesired byproduct. other aryl iodides as wel . Again, when we examined carbonylative amidation of iodobenzene with diethyl amine, our microflow system gave greater double-carbonylation selectivity as well as higher mono+double-carbonylation yield compared to the autoclave reactor.


Fukuyama, T.; Shinmen, M.; Nishitani, S.; Sato, M.; Ryu, I. Org. Lett. 2002, 4, 1691. This land-mark paper has more than 200 times citation for a short period of time.
Liu, S.; Fukuyama, T.; Sato, M.; Ryu, I. Synlett. 2004, 1814.
Liu, S.; T. Fukuyama, T.; Sato, M.; Ryu, I. Org. Process Res. Dev. 2004, 8, 477.
Rahman, M. T.; Fukuyama, T.; Kamata, N.; Sato, M.; Ryu, I. Chem. Commun. 2006, 2236.
Review: Fukuyama, T.; Rahman, M. T.; Sato, M.; Ryu, I. Synlett (Accounts) 2008, 151.


Microflow Synthesis of Organic Molecules by Efficient Radical Reactions

Relying upon high thermal efficiency of microreactors, we found that tin hydride mediated radical cyclization proceeded in one minute.


Having a nice collaboration with the Studer group, we found that thermal addition reaction of TEMPO-derivatives across C-C double bonds proceeded without being bothered by the further reaction. The following example demonstrated that microflow conditions overwhelmed microwave/batch conditions.


Radical carbonylation also can be achieved using continuous microflow reaction.


Photo-reactions are among most suited to microflow reactors. We found that low power UV LED suffices the following photo-induced Barton reaction.


Fukuyama, T.; Kobayashi, M.; Rahman, Md. T.; Kamata, N.; Ryu, I. Org. Lett. 2008, 10, 533.
Wienhoefer, I. C.; Studer, A.; Rahahman, M. D.; Fukuyama, T.; Ryu, I. Org. Lett. 2009, 11, 2457.
Sugimoto, A.; Fukuyama, T.; Takagi, M.; Sumino, Y.; Ryu, I. Tetrahedron 2009, 65, 1593-1598.
Fukuyama, T.; Rahman, M. T.; Kamata, N.; Ryu, I. Beilstein J. Org. Chem. 2009, 5, 34.

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Laboratory for Advanced Organic Synthesis
Organization for Research Promotion Osaka Prefecture University
Sakai, Osaka 599-8531, JAPAN
Mail:ryu --at-- Replace @ instead of  "--at--".