Transcript Shu Kobayashi Professor, University of Tokyo

Shu Kobayashi
Professor, University of Tokyo
Shu Kobayashi
Shu Kobayashi
Takeru 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)
JST : Japan Science and Technology
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ERATO
: Exploratory
Research
for Advanced
Technology
oh yeah France
1993
: Visiting
Professor,
Universite
Louis Pasteur,
Strasbourg,
1995
: Visiting
Professor,
University
SORST
: Solution
OrientedKyoto
Research
for Science and Technology
1996
: Visiting
Nijmegen
University,
Netherlands
CREST
: Core professor,
Research for
Evolutionary
Science The
and Technology
1997 : Visiting Professor, Phillipps-Universitat Marburg, Germany
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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-)
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MAJOR AWARDS
EDITORIAL APPOINTMENTS
2006 Howard Memorial Lecturer
2006 Arthur C. Cope Scholar Awards
2005 JSPS Prize
2005 Mitsui Chemical Catalysis Science Award
2004 Manchester-Merck Lecturer
2003 Novo-Nortis Lectureship
2002 Nagoya Silver Medal
2002 Organic Reactions Lecturer
2001 Roche Lectureship
2001 NPS Distinguished Lecturer
2001 IBM Science Award
2000 Novartis Chemistry Lectureship
2000 MIT/Wyeth-Ayerst Lectureship
2000 Nagoya Lectureship
1999 Bio-Mega/Boehrinder Ingelheim Lecturer
1999 Merck-SFC Lectureship
1999 Wyeth-Ayerst Lectureship
1997 Springer Award in Organometallic Chemistry
1995 Kurata Research Foundation
1994 Ciba-Geigy Research Foundation
1993 Nissan Science Foundation for Younger
Generation
1992 New Chemistry Institute Research Award
1992 Teijin Award in Synthetic Organic Chemistry,
Japan
1991 The Chemical Society of Japan Award for
Young Chemists
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 Interests
Organic reactions in water
Development of Chiral Catalysts
Synthesis of Biologically
Important Molecules
Polymersupported/incarcerated
Catalysts
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Organic reactions in Microchannels
Microreactors (lab-on-a-chip)
Lab-on-a-chip
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
Chips-in-a-lab…yum!
Chips-on-a-bike (1977-1983)
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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
O2 (0.1 MPa)
Polymer Incarcerated Ru (5 mol %)
TEMPO (15 mol %)
R
OH
1, 2 DCE, 80 C, 2.5 hrs
R
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
H2 (1 atm)
Polymer Incarcerated Pd (5 mol %)
Starting material
Product
THF, rt
Okamoto, K. ; Akiyama, R. ;
Kobayashi, S.
J. Org. Chem. 2004, 69,
2871-2873
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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 optimization
O
+
OMe
NH2
Catalyst (5 mol %)
H2O, rt, 24 hr
N
Me
PMO
NH
2 Np
N
Me
4a
2 Np
N
Me
5a
2
OMP = ortho-methoxyphenyl
DS = dodecyl sulfate
DBSA = dodecylbenzenesulfonic
acid
Length of alkyl chain crucial
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Scope
R4
R3
C9H19CO2H
(10 mol %)
H2O, rt, 24 hr
N
R2
+
R4
R3
H
CDI (2 equiv.)
Sc(OTf)3 (10 mol %)
PhMe, 70 C, 3 hr
R1
NH2-OMP
H N
R4
R3
N
R2
N
R2
O
R1
N
PMO
H NH
R1
O
OMe
N
N
H
6a
6b
N
6c
N
6d
Br
N
Et
N
N
N
N
CDI
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
Dehydrative C-C bond formation in water
Reaction on benzylic alcohols
Poor leaving ability of hydroxy group compared to halides
Dehydrations in water…of course Kobayashi!
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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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