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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