1 shu kobayashi professor, university of tokyo takeru kobayashi shu kobayashi david tilly,...
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Shu KobayashiProfessor, University of Tokyo
Takeru KobayashiShu KobayashiShu Kobayashi
David TILLY, Literature seminar, 19 August 2008
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Since 2003, he is a director of ERATO project (JST) Since 1998 : Professor in the Graduate School of Pharmaceutical Sciences at the University of Tokyo
I look great on this pic
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Education and Academic career• 1983 : B.Sc.; The University of Tokyo (Professor Teruaki. Mukaiyama)• 1987 : Ph.D.; The University of Tokyo (Professor Mukaiyama)
• 1988 : Assistant Professor; Science University of Tokyo (SUT)• 1991 : Lecturer ; Science University of Tokyo (SUT)• 1992 : Associate Professor; Science University of Tokyo (SUT)
• 1993 : Visiting Professor, Universite Louis Pasteur, Strasbourg, France• 1995 : Visiting Professor, Kyoto University• 1996 : Visiting professor, Nijmegen University, The Netherlands• 1997 : Visiting Professor, Phillipps-Universitat Marburg, Germany
• 1997 : Special promoted Researcher (SUT, 1997-1998)• 1997 : CREST Investigator (JST, 1997-2001)• 1998 : Full Professor, The University of Tokyo• 2002 : SORST Investigator (JST, 2002-2004)• 2003 : ERATO Investigator (JST, 2003-)
JST : Japan Science and Technology
ERATO : Exploratory Research for Advanced Technology oh yeah
SORST : Solution Oriented Research for Science and Technology
CREST : Core Research for Evolutionary Science and Technology
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MAJOR AWARDS
2006 Howard Memorial Lecturer 2006 Arthur C. Cope Scholar Awards2005 JSPS Prize2005 Mitsui Chemical Catalysis Science Award2004 Manchester-Merck Lecturer2003 Novo-Nortis Lectureship2002 Nagoya Silver Medal2002 Organic Reactions Lecturer2001 Roche Lectureship2001 NPS Distinguished Lecturer2001 IBM Science Award2000 Novartis Chemistry Lectureship2000 MIT/Wyeth-Ayerst Lectureship2000 Nagoya Lectureship1999 Bio-Mega/Boehrinder Ingelheim Lecturer1999 Merck-SFC Lectureship1999 Wyeth-Ayerst Lectureship1997 Springer Award in Organometallic Chemistry1995 Kurata Research Foundation1994 Ciba-Geigy Research Foundation1993 Nissan Science Foundation for Younger Generation1992 New Chemistry Institute Research Award1992 Teijin Award in Synthetic Organic Chemistry, Japan1991 The Chemical Society of Japan Award for Young Chemists
EDITORIAL APPOINTMENTS
Associate Editor, Journal of Combinatorial Chemistry (1999-)Associate Editor, Advanced Synthesis & Catalysis (2000-)Editorial Advisory Board, Molecules Online (1997-2000)Editorial Advisory Board, Synthesis (1999-)Editorial Advisory Board, Chemical Reviews (2000-) Organic & Biomolecular Chemistry, Editorial Board (2002-)
5000 US Dollars for himself
40 000 US Dollars as unrestricted research grant
YAY!
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Research InterestsOrganic reactions in water Development of Chiral Catalysts
Synthesis of Biologically Important Molecules
Polymer-supported/incarcerated Catalysts
Organic reactions in Microchannels Microreactors (lab-on-a-chip)
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Lab-on-a-chip
Chips-on-a-bike (1977-1983)
Chips-in-a-lab…yum!
Device that integrates one or several laboratory functions on a single chip of only millimeters to a few square centimeters in size. LOCs deal with the handling of extremely small fluid volumes down to less than pico liters
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“A microfluidic Device for Conducting
gas-liquid-solid Hydrogenation Reactions”
Juta Kobayashi, Yuichiro Mori, Kuniaki Okamoto, Ryo Akiyama, Masaharu Ueno, Takehiko Kitamori, Shu Kobayashi
Science 2004, 304, 1305-1308
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Immobilization of Pd catalyst on the glass surface
Microencapsulation of Pd catalyst
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• Yields quantitative
• No Pd leaching
• 0.01mmol/hr
•No loss of activity is chip is reused
•Scale up possible by using chips in parallel
•P H2=1 atm
• For a recent review of microchannel reactors in organic synthesis, see :
Chem. Asian. J. 2006, 1-2, 22-35
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“Polymer Incarcerated Ruthenium Catalyst for Oxidation of Alcohols with Molecular Oxygen”
Tsutomu Matsumoto, Masaharu Ueno, Juta Kobayashi, Hiroyuki Miyamura, Yuichiro Mori, Shu Kobayashi
Adv. Synth. Catal. 2007, 349, 531-534
R OH
O2 (0.1 MPa)Polymer Incarcerated Ru (5 mol %)TEMPO (15 mol %)
1, 2 DCE, 80 C, 2.5 hrsR O
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Polystyrene based copolymer
Choice of Ru important to avoid leaching and high catalytic activity
1- polymer micelle incarcerated Ru catalyst
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Effect of Ruthenium Source
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Scope
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Recovery of Polymer Incarcerated Ru Catalyst
Simple filtration, wash with DCM and drying of the solid to recover the catalyst
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Application to Hydrogenation reactions
Okamoto, K. ; Akiyama, R. ; Kobayashi, S.
J. Org. Chem. 2004, 69, 2871-2873
H2 (1 atm)Polymer Incarcerated Pd (5 mol %)
THF, rtStarting material Product
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Chemistry in water…very refreshing!
“Carboxylic Acid Catalyzed Three-Component Aza-Friedel-Crafts Reactions in Water for the Synthesis of 3-Substituted Indoles”
Seiji Shirakawa and Shu Kobayashi
Org. Lett. 2006, 8, 4939-4942
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A look at the reaction in water
Aza Friedel Crafts reactions are difficult to control
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Acid Catalyst optimizationO
OMe
NH2
+NMe
Catalyst (5 mol %)H2O, rt, 24 hr
NMe
NH2 Np
PMO
NMe
2 Np
24a 5a
OMP = ortho-methoxyphenyl
DS = dodecyl sulfate
DBSA = dodecylbenzenesulfonic acid
Length of alkyl chain crucial
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Scope
NR2
R3
R4
R1 H
O
NH2-OMP
+
C9H19CO2H(10 mol %)H2O, rt, 24 hr
NR2
R3
R4
NHR1
HPMO
CDI (2 equiv.)Sc(OTf)3 (10 mol %)PhMe, 70 C, 3 hr
NR2
R3
R4
NR1
H
N
NN
N
O
N
CDIN N
HN N N
Et
OMe Br
6a 6b 6c 6d 6e
No metal
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Further transformations
CN bonds very reactive, can react with various nucleophiles in presence of DBSA or Sc(OTf)3
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“Surfactant-Type Brønsted Acid Catalyzed Dehydrative Nucleophilic Substitutions of Alcohols in Water”
Seiji Shirakawa and Shu Kobayashi
Org. Lett. 2007, 9, 311-314
Dodecylbenzenesulfonic acid
Dehydrations in water…of course Kobayashi!
Dehydrative C-C bond formation in water
Reaction on benzylic alcohols
Poor leaving ability of hydroxy group compared to halides
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Substitution of benzhydrols : scope of nucleophiles
Both surfactant property and Bronsted acidity of DBSA are essential to promote the reaction efficiently
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Substitution of Benzyl Alcohols : scope of alcohol starting material
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Extention of the scope : C-Glycosylation of 1-hydroxy sugar
Excellent B selectivity
Compound 3b is an intermediate in the synthesis of Showdomycin
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Concluding Remarks
•Conceptually different approach to organic chemistry
•Addresses issues of “green chemistry”
•Research covers broad scope of topics in chemistry
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