Baran Group Meeting
Prof. Shu Kobayashi
Hai Dao
04/20/2013
Shu Kobayashi
1959 Born in Tokyo, Japan
1983 B.Sc.; The University of Tokyo (UT); Prof. T. Mukaiyama
1988 Ph.D.; The University of Tokyo; Prof. T. Mukaiyama
1987 Assistant Professor; Tokyo University of Science
1991 Lecturer; Tokyo University of Science
1992 Associate Professor; Tokyo University of Science
1998 Professor; UT; Graduate School of Pharmaceutical Sciences
2007 Professor; UT; Department of Chemistry, School of Science
Important Honors and Awards
1991 The Chemical Society of Japan Award for Young Chemists
1997 Springer Award in Organometallic Chemistry
2001 IBM Science Award
2002 Nagoya Silver Medal
2005 Mitsui Chemical Catalysis Science Award
2006 Arthur C. Cope Scholar Awards
2006 C.S. Hamilton Award
Publications
>600 Publications (c.a 60 Reviews)
Science (1); JACS (66); Angew (34)
Web of Knowledge data(03/2013):
average citations: 52.32
H-index: 86
Most cited works:
Chem. Rev. 1999, 1069: 1061 times
Synlett. 1994, 689: 601 times
Major Research Interests:
Novel Chiral catalysis
Organic reaction in water
Polymer supported catalysis
Organic reaction in microreactors
Doctoral years at UT with Prof. Mukaiyama
OBn
OBn
O
BnO
BnO
O
OBn
O
+ 3β-Cholestanol
TrClO4 (stoichiometric)
(Tr = Ph3C)
BnO
BnO
Lewis acid catalysts: TrClO4; TrCl-SnCl2,
SbCl4-Sn(OTf)2; SnCl4-Sn(OTf)2
O
OBn
CH2Br
O−Cholestanyl
His first publication Chem. Lett. 1984, 907.
Sn(OTf)2, TBAF,
Ph
CHO
+
OTMS
SEt
(stoichiometric)
N
Me
for various catalytic C−C bond formations:
Aldol reactions, Michael Reaction...
N
OH
DCM, -78 oC; 78%, 82% ee
Ph
O
SEt
Among the first examples of asymmetric
aldol reactions between prochiral silyl
enol ethers and prochiral aldehydes
His first asymmetric reaction Chem. Lett. 1989, 297.
JACS, 1991, 4247.
First Independent publication
OSiMe3
Ph
Yb(OTf)3 (1 mol%)
90%
Lanthanide trifluoromethanesulfonates
as stable Lewis acids in aqueous
media. Recovery and reuse of catalysts
from aqueous layer.
O
(CH2O)aq, THF
Ph
OH
Me
Chem. Lett. 1991, 2187.
Baran Group Meeting
Part 1. Chiral Catalysis
Sn(OTf)2
OSiMe3 chiral amine
N
Me
SEt
OH
R
OH
Bu2Sn(OAc)2
OTBS
DCM, −78 oC
chiral amine = L1
(stoichiometric) 86%, 98% ee
syn:anti = 98:2
R
SEt
L2
O
H3C(H2C)9
Sn N
N
Me
OH
O
CO2H
Br
application to enantioselective total synthesis of D-erythro-Sphingosine
(Tetrahedron Lett. 1994, 9573.); sphingofungin B (synlett 1996, 672.);
khafrefungin (J. Am. Chem. Soc. 2001, 1372)...
O
O
Zr
O
O
R1
R2
LA
R1
Sc, Y,
Ln, Zr, Nb
H
O
J. Am. Chem. Soc. 1997, 7153.
N
N
R1
Nu
O
Cu cat.
EtO
O
N-acyliminoesters
N
EtO
R2
Ph
NH
CuL*
O
X
R
Ph
HN
X = OR; NHR
R
R
nucleophiles diamine ligands
Mannich type: Org. Lett. 2002, 143;
J. Am. Chem. Soc. 2003, 2507;
J. Am. Chem. Soc. 2004, 6558.
Aldol-type: Angew. Chem. Int. Ed. 2004, 3258;
Allylation: Angew. Chem. Int. Ed. 2006, 1615.
Review: Acc. Chem. Res. 2008, 292.
LA
N
R2
OMe
Copper Catalysts
R
- Lewis acid - imine interaction is not regid => difficult to
make it enantioselective
LA
Ph
Strecker reaction (dinuclear cat.): Angew. Chem. Int. Ed. 1998, 3186
Hetero D-A reaction: J. Am. Chem. Soc. 1999, 4220; J. Am. Chem. Soc.
2003, 3793.
Aldol reaction: J. Am. Chem. Soc. 2002, 3292.
[3+2] cycloadition: J. Am. Chem. Soc. 2004, 11279.
Isolable, air-stable, storable Zr catalyst: J. Am. Chem. Soc. 2006, 11232.
100 gram-scale synthesis of Vancomycin's building block using Zirconium
catalyst: Adv. Synth. Catal. 2006, 1831.
O
- Lewis acids are trapped by the basic nitrogen atoms of
the starting materials/products => difficult to make it catalytic
N
OMe
NH2 O
Br
Challenges in Lewis acids catalyzed enantioselective reaction with imines
R
Ph
1. MeI, K2CO3
2. CAN
83%
Br
Zirconium Catalysts for Addition to Imines
R
O
Yb catalysts for (aza)-Diels-Alder reactions: Synlett, 1994, 689.
Nb catalysts for stereoselective ring opening of meso-epoxides and mesoaziridines: J. Am. Chem. Soc. 2007, 8103.
OH
khafrefungin
oC
H
J. Am. Chem. Soc. 1994, 9805
HO
O
NMI, DCM, −45
70%, 87% ee
catalyst
R
OH
NH
Br
O
H
H
chiral amine = L2
82%, 98% ee
syn:anti = 99:1
N
N Sn
Me O
OMe
catalyst (10 mol%)
OTBS
R
N
+
N
Ph
O
OSiMe3
NMI = N-methylimidazole (sub-stoichiometric)
N
L1
N
Me
O
+
SEt
OH
HO
Chiral Lewis Acid Catalysis for Activation of Electrophiles
Tin Catalyst: (CLAC synthesis: chiral Lewis acids controlled synthesis)
RCHO +
TBSO
Hai Dao
04/20/2013
Shu Kobayashi
O
nC
11H23
HO
NH
OH
Ph
HPA-12
(3 steps, 82.9 % yield)
Baran Group Meeting
Hai Dao
04/20/2013
Shu Kobayashi
Activation of Nucleophiles: "Catalytic Carbanion Reaction"
H
OML*
M+B-
O
OR
OR
BH
+
OH
R1CHO
R1
BH
M+B+
direct aldol reaction: M B = catalyst
*
NO2 +
MeO
Ph
O
Ca(OAr)2 (10 mol%)
ligand (10 mol%)
O
O
OMe
OR
toluene, −20 oC
80%, 96% ee
O
O
OMe
MeO
NO2
Ph
Pyridinebisoxazoline (Pybox) Ligands:
- neutral coordinative ligands: stronger
Ph
Ph
N
N
Bronsted bacicity of the complexes
Ca
- three coordination number => more
Ph
Ph
RO OR
rigid complexes = high ee
Pybox-calcium alkoxide complexes
Angew. Chem. Int. Ed. 2009, 9117.
N
Alkaline Earth Metal Catalysts
O
Mannich reaction: J. Org. Chem. 2010, 963.
Michael reaction: J. Am. Chem. Soc. 2010, 7890.
Strontium Catalysis: J. Am. Chem. Soc. 2008, 2430.
Picture from Harder, S. Chem. Rev. 2010, 3852. Barium Catalysis: J. Am. Chem. Soc. 2006, 8704.
Alkaline Earth Metal Compounds:
Review for Alkaline Earth Metal Catalysis: Acc. Chem. Res. 2010, 58.
- low electronegativity = stronger Bronsted basicity of counter anion =>
Silver Catalysis: silver amide with phosphine ligand for [3+2] cycloadditions:
based-catalyzed reactions
Angew. Chem. Int. Ed. 2011, 4893. J. Am. Chem. Soc. 2012, 20049.
- Highl nucleophilicity (as of group 1)
- Significant Lewis Acidity (as of group 3) => substrate binding for high ee
Modification of Nucleophiles
- Large ionic radius (Ca2+, 1.00Å; Sr2+, 1.18Å; Ba2+, 1.35Å; ) => large number
Fluorenone Schiff Base
of coordination sites => challenges in chiral modification for high ee
Asymmetric Calcium Catalysis
O
O
+ Ph
OMe
O
O
N
Ph
N
OMe
Ph
2 (10 mol%)
ligand (10 mol%) Ph
−30 oC, THF
quant., 83% ee
N
N
*
Ph
O
O
N
Ca(OR)2
Ph
N
Ca
OR
O
N
Ph
Ph
N
Ca
OR
*
Ph
O
OMe
N
N Ca
R
N
base
OMe
R
Ph
14π-e aromatic anions
Mannich-type reaction: (R = COOMe) Angew. Chem. Int. Ed. 2008, 5613.
(R = alkyl, aryl) J. Am. Chem. Soc. 2010, 3244.
Sulfonylimidates as Nucleophiles
Ph
O
N
fluorenone imines
N
Ph
a Box ligand
COOMe
N
N Ca
N
Ph
OMe
Ph
Schiff base
low pKa
O
O
Ca(OiPr)
O
Ph
N
Box-calcium alkoxide complexes
OMe
Bisoxazoline (Box) Ligands:
Ph
pros: covalence/ionic bond = strong interaction
chiral calcium enolate
cons: decrease in Bronsted basicity of
the complexes
J. Am. Chem. Soc. 2007, 5364
Mannich-type reaction, Michael-type reaction:
(DBU) J. Am. Chem. Soc. 2008, 1804. (alkaline earth
base). Angew. Chem. Int. Ed. 2009, 6041.
(organosuperbase). Angew. Chem. Int. Ed. 2012,
9525.
Tsuji-Trost Reaction: Chem. Commun. 2008, 6354.
Review: Chem. Eur. J. 2009, 10694.
picture from Chem. Eur. J. 2009, 10694.
Baran Group Meeting
Shu Kobayashi
Other Chiral Catalysis - Allylation
Neutral Coordinate Organocatalysts (NCOs)
Part 2. Organic Reaction in Aqueous Media
Initial Finding
O
Ln(OTf)3 and Sc(OTf)3 = Stable Lewis Acids in Aqueous Media
ptolyl
HN
(3 equiv.)
SiCl3
+
Ph
S
Me
NHBz
N
DCM, −78 oC
73%, 93% ee
H
NHBz
Ph
Enantioselective Transfer Aminoallylation
OH
HOOC
O
rt, 5min
72%, 87% ee
OH
OOC
NH
O
O
O
O
mol%)
NHBz
HN
* (5 mol%)
L
B(pin)
PhMe, MeOH, 0 oC Ph
99%, 96% ee
+
H
Ph
L*−InI
CN
O
Ph
O
N
Ph
Both Yb and water
are important
OMe Yb(OTf)3 (10 mol%)
Me
THF-H2O (9:1)
92%
pClC
O
6H4
Me
COO
Sc
4.3
4.8 107
hydrolysis constant (pKh)
inner-sphere water ligands
exchange rate constant (WERC)
base
B(pin)
Ph
HN
L*
Ph
THF-H2O (4:1)
91%
- HOTf (various pH): low conversions
- In THF only or water only: low conversions
Systematic Studies of Various Lewis Acid Catalysis in Water
InII(5
NHBz
O
Interesting finding:
Cu(OTf)2 = Excellent Catalyst for Aldol Reaction and Allylation in Aqueous Media
J. Am. Chem. Soc. 2006, 11038. Chem. Lett. 1997, 959. How about other metals?
Transmetallation(TM) (In, Zn, Ag)
N
OH
Yb(OTf)3 (10 mol%)
first ex. in aqueous media: J. Chem. Soc., Chem. Commun., 1995, 1379.
Michael reaction, allylation, Diels-Alder reaction: Synlett, 1994, 689
NH
COO
+
HCHO + pClC6H4NH2 +
B(pin)
NH3
OSiMe3
Mannich-type reaction
NH3
EtOH
+
Aldol reaction
PhCHO
J. Am. Chem. Soc. 2003, 6610. Adv. Synth. Catal. 2004, 1023.
NH2
Hai Dao
04/20/2013
L*−InI
Ph
transmetallation
E
L*−In
the active nucleophile
Angew. Chem. Int. Ed. 2010, 1838. Acc. Chem. Res. 2012, 1331.
pKh = 4.3−10.08; WERC > 3.2 106M-1s-1 J. Am. Chem. Soc. 1998, 8287.
Baran Group Meeting
Shu Kobayashi
Hai Dao
04/20/2013
Catalytic Asymmetric Reaction in Aqueous Media Catalyzed by Ln(OTf)3
- large ionic radius, large number of coordination sites = challenging
M(OH)2+ + 2H+
Kh =
Challenges
in designing a chiral ligand for Ln(OTf)3 :
[M2+]
pKh = -logKh
- too strong coordinating ability => reduction of Lewis acidity
WERC: measured by NMR, sound absorption, or multidentate legand method - too weak coordinating ability => low ee due to achiral free L.A pathways
Martell, A. E., Ed.; Coordination Chemistry, ACS Monograph 168; ACS:
Washignton, DC, 1978; Vol.2.
- Pr(OTf)3 (10 mol%) Ligand 3 (12 mol%), 0 oC:
N
(2R, 3R), 85%, 78% ee, syn:anti = 91:9.
Study Objectives: Effect of Metal Salts in the Yields of Aldol Reaction
O
O
- first example of Ln(OTf)3 in catalytic asymmetric
OH O
aldol reactions in aqueous media (10 year for the
OSiMe3
MXn (0.2 eq.)
O
O
asymmetric version vs. Chem. Lett. 1991, 2187.)
PhCHO +
Ph
Ph
N
THF-H2O (9:1)
Ph
- ee and dr are highly dependent on the size of
Me
rt, 12h
lanthanides: size fitting effect of macrocyclic ligands
Yields > 50%: pKh = 4.3−10.08; WERC > 3.2 106M-1s-1
Org. Lett. 2001, 165. J. Am. Chem. Soc. 2003, 2989.
Explanation:
Ligand 3
pKh < 4.3: fast hydrolysis, formation of proton => decomposition of enol ether Catalytic Asymmetric Reaction with Aqueous Formaldehyde
pKh > 10.08: cation is too stable, low Lewis acidity
Sc(OTf)3 (10 mol%)
O
Small WERC: slow reaction as Lewis acids need to coordinate with substrate
OSiMe3
Ligand 4 (12 mol%)
Ph
OH
+ aq. HCHO
Ph
Catalytic Enantioselective Aldol Reaction
oC
H
O/DME
=
1/9,
−
20
2
Me
(5 equiv.)
89%, 90% ee
M(OTf)
(x
mol%)
OH
O
2
OSiMe3
Ligand (y mol%)
PhCHO +
- use commercial available formalin
Ph
Ph
N
N
Ph
H2O-EtOH (1/9), temp
- high yields and enantioselectivities
tBu
tBu
Me
J. Am. Chem. Soc. 2004, 12236.
OH
HO
Ininitial Finding with Cu(II) and Pb(II)
(2S, 3S)
Ligand 4
Cu(OTf)2 (20 mol%); Ligand 1 (20 mol%), −10 oC:
O
O
Enantioselective Mannich-type Reaction
(2S, 3S), 74%, 67% ee, syn:anti = 3.2:1.
NHBz
N
N
first example of catalytic asymmetric aldol reaction in
NHBz
N
ZnF2(100 mol%)
HN
O
aqueous media; Chem. Lett. 1999, 71.
Ph
Ph
OSiMe3
ligand
5
(10
mol%)
Ligand 1
EtO
EtO
H +
C6H4pMe
C6H4pMe
H2O, 0 oC
Pb(OTf)2 (20 mol%); Ligand 2 (24 mol%),
O
O
91%, 95%ee
oC: (2S, 3S), 62%, 55% ee, syn:anti = 9:1.
0
acylhydrazono ester
O
first example of chiral crown-based Lewis
O
O
- additives such as cetyltrimethylammonium
Ph
Ph
acid in catalytic asymmetric reactions ;
bromide is needed in some cases
O
O
J. Am. Chem. Soc. 2000, 11531.
NH HN
OMe - first enantioselective Mannich-type reactions
MeO
in Water
O
the same level of reaction rate to Pb(OTf)2
J. Am. Chem. Soc. 2004, 7768.
catalyzed achiral reaction
Ligand 2
Ligand 5
Hydrolysis constant
M3+ + 2H2O
[M(OH)+]
[H+]2
Baran Group Meeting
Part 3. Surfactant-Type Catalyst
Other Organic Reaction in Aqueous Media
Pd-Catalyzed Allylic Amination Using (aq.) NH3 for Primary
Amines Synthesis
Ph
Ph
aq. NH3/1,4-dioxane (1/2)
0.04M, rt, 18 h
71%, 87% ee
NH3 gas: NR
Lewis Acid Surfactant Combined Catalysts (LASCs)
A New Idea for Catalysis in Water:
Surfactants: for better solubility of sub.
[PdCl(allyl)]2 (5 mol%)
(R)-BINAP (20 mol%)
OAc
Hai Dao
04/20/2013
Shu Kobayashi
NH2
Ph
Ph
LASC for
Organic Synthesis
in Water
Stable Lewis acids in water = catalysts
?
Synthesis of LASCs
ScCl3 + 3RSO3H
1: Sc(O3SOC12H25)3
Sc(RSO3)3
2: Sc(O3SC12H25)3
- Previous thinking "ammonia fails to act as an effective nucleophile for
π-palladium" . Godleski, S. A. In Comprehensive Organic Synthesis;
Trost, B. M., Ed.; Pergamon: Oxford, U.K., 1991; Vol. 4, p 585:
+ amonia deactivates transition metal catalyts
+ overreaction to secondary/tertiary amines
- Polar solvent, diluted conditions and an excess amount of ligands are
critical
- First example of Pd-catalyzed allylic amination using aqueous NH3 for
synthesis of primary amines. J. Am. Chem. Soc. 2009, 4200.
Catalytic Asymmetric Allylation of Aldehydes in Aqueous Media
PhCHO +
B
OSiMe3
Zn(OH)2 (10 mol%)
Ligand 4 (12 mol%)
O
O
OH
Me
Ligand 4 (see previous page)
O
OH
PhCHO +
water
O
Ph
H2O, rt, 4h Ph
1.5 equiv.
92%
Me
DCM, DMF, MeOH, neat.: low yields
inital rate in water = 1.3 102 times in DCM
92%, 81% ee
syn:anti = 10:1
Reaction Mechanism
- in organic solvents: uncatalyzed reaction of allylboronate and aldehydes
- in aqueous solvents: the uncatalyzed reaction is suppressed,
transmetallation mechanism is proposed:
E
ZnL
active species
base
Zn(II)L
O
fast
B
1 (10 mol%)
LASC 2 :PhCHO
= 1 :20 (16.7mM)
Ph
LASCs
1.0 equiv.
Ph
H2O/MeOH = 3:7
0 oC, 1h
Me
LASC and organic substrates in water:
formation of the colloidal particles
Catalytic Aldol Reaction
products
centrifugation
reaction occurs
at the interface
ZnL
Me
Zn catalysts: Angew. Chem. Int. Ed. 2011, 12262.
with and without stirring
Mannich-type reaction, allylation: J. Am. Chem. Soc. 2000, 7202.
Baran Group Meeting
Hai Dao
04/20/2013
Shu Kobayashi
Bronsted Acid Surfactant Combined Catalysts (BASCs)
The concept for dehydrative esterification in water
Chiral LASCs for Catalytic Asymmetric Reaction with a
Hydrophobic Substrates
OSiMe3
+ aq. HCHO
(5 equiv.)
N
Screening of Catalysts
catalyst
(10 mol%)
N
tBu
tBu
OH
HO
Sc(DS)3 (10 mol%)
Ligand (12 mol%)
H2O (0.5M)
then reduction
with Pt cat./H2
56%, 91% ee
OH
artificial odorant
Merging between chiral Lewis acid
in water and LASCs concepts
Angew. Chem. Int. Ed. 2008, 6909.
CH3(CH2)10CO2H + HO(CH2)3Ph
CH3(CH2)10CO2(CH2)3Ph
H2O, 40 oC, 24 h
(1:1)
Surfactants for Reactions in supercritical Carbon Dioxide
DBSA-substrates
catalysts
yields (%)
(scCO2)
Yb(OTf)3 (5 mol%)
Sc[O3S(CH2)10CH3]3
15
NHBnO
OSiMe3
NBn
additive (4g/L)
Yb[O3S(CH2)10CH3]3
4
+
Ph
OMe
OMe
scCO2
Ph
C12H25C6H4SO3H (DBSA)
60
50 oC, 15MPa, 3h
low solubitities in scCO2
C8H17C6H4SO3H (OBSA)
39
none: 10%; poly(ethylene glycol) = surfactant: 72%
H SO , TfOH
<5
2
Ligand
4
C12H25C6H4SO3Na
Aldol reactions, Fridedel-Crafts reactions: J. Org. Chem. 2004, 680.
2
the reaction in neat conditions is faster but the same equilibrium is obtained
Part 4. Polymer-supported Catalysis
Why Immobilize the Catalysts
- green chemistry: less waste, reuse of catalyst
DBSA CH (CH ) CO (CH ) CH (A)
3
2
10
2
2
11
3
- high-throughput synthesis: simple work-up and separation
CH3(CH2)10CO2H
(10 mol%)
+
procedure = fast access to large number of compounds
+ CH3(CH2)11OH
o
CH CO H
Selective Esterification
40 C, 48 h
CH3CO2(CH2)11CH3 (B)
(1:1:1)
neat: A = 63%; B = 35%; in H2O: A = 81%; B = 4%
3
2
Transesterification
+
CH3(CH2)10CO2Me
DBSA (10 mol%)
CH3(CH2)11OH
40 oC, 48 h, 90%
CH3(CH2)10CO2(CH2)11CH3
dehydration, Mannich-type, Substitution: Synlett. 1999, 1401.
J. Am. Chem. Soc. 2002, 11971. Org. Lett. 2007, 311.
Initial Works: Polymer-Supported Sc = Lewis Acid Catalysts
F2
C
O
S
O
OScX2
Nafion-Sc
J. Org. Chem. 1996, 2256.
H2 H
C C
H2 H
C C
CN n
CH2NTf n
polyacryronitrile derivative
Sc(OTf)2
J. Am. Chem. Soc. 1996, 8977.
Lewis acids for : (aza)-Diels-Alder, Friedel-Crafts reactions
Baran Group Meeting
Microencapsylated Osmium Tetroxide [MC OsO4]:
Drawbacks of Coordinate Bonds Polymers:
- Low stability
- Preparation can be troublesome
- Lower reactivity (vs. monomer catalysts)
Alternative Idea of Immobilized Catalysts:
Microcapsules
- coating and isolating substances
in food and pharmaceutical
industry
- many techniques have been developed
screening:
initial catalyst:
n
Instead of Using Coordinate
Bonds, Why not
Immobilize Catalysts
in Microcapsules ?
Borrow the idea form coacervation-phase separation teachniques (a
physio-chemical method in microcapsule), general procedure:
CN
y
x
z
poly(acryronitryl-co-butadiene-co-styrene)
(used for coating medicine)
[PS-MC OsO4]
[ABS-MC OsO4]
good
yield
and
high ee with NMO
- first polymer-supported Os cat.
- olefin moiety of butadiene was oxidized to
-good recovery and reuse
- not good for asymmetric
form hydrophilic polymer: effetive in
transformation
asymmetric reaction
- leaching of OsO4 when K3Fe(CN)6 is used
(hydrophilic solvents and diol of polymer)
design:
incoporate less polar groups to the polymer
II
I
Hai Dao
04/20/2013
Shu Kobayashi
x
y
NaO
OPh
x
y
interaction between π−electron of and vacant orbitals of metal
THF, 80 oC, 12h
quant.
1. polymers are dissolved in appropriate solvent at high temp.
OPh
x
=
0.05
2. catalysts are added and stirred
Cl
O
y = 0.95
3. cool down for coaservation (I: phase separation)
4. wash and dry (II)
poly(4-phenoxyethoxymethylstyrene-co-styrene) [PEM-MC OsO4]
J. Am. Chem. Soc. 1998, 2985.
Chem. Commun. 2003, 449 and related references - good yields and high ee for asymmetric hydroxylation with K3Fe(CN)6
- no leaching of OsO4
Microencapsulated Sc(OTf) [PS-MC Sc(OTf) ]:
3
3
- aldol, imino-aldol, Diels-Alder, Friedel-Crafts, Mannich, Strecker... reactions
- reactivity is as good or better (imino-aldol) than monomer
- both in batch and flow system
- Control experiments for the amount of immobilized Sc(OTf)3 : polystyrene
100%; polybutadiene 43%; polyethylene 0% : π-electron-Metal interaction
PhCHO + PhNH2 +
Ph
OSiMe3
Me
flow system: reuse 3 times, >90%
MC Sc(OTf)3
(ca. 0.5 equiv.)
Ph
MeCN, rt, 3h
high yield
Ph
NH
O
Ph
PEM-MC OsO4 (5 mol%) K3Fe(CN)6 (2 equiv.),
OH
K2CO3 (2 equiv)
(DHQD)2PHAL (5 mol%)
OH
Ph
H2O-acetone (1/1)
3h
K3Fe(CN)6 (2 equiv.),
OsO4: quant. recovery
K2CO3 (2 equiv), 30 oC, 5 h
ligand: >95% recovery
1st: 85%, 78% ee; 2nd: 66%, 78% ee; 3rd: 84%, 78% ee
Ph
Me
[MC Pd(PPh3)] for cross coupling and other [MC metal]: Chem. Commun.
2003, 449 and related references
Baran Group Meeting
Hai Dao
04/20/2013
Shu Kobayashi
Second Generation: Polymer Incarcerated (PI)
MC catalyst
MC catalysts are dissolved or swelled
after reactions => leaching of metals
[PI OsO4] catalyst
Polymer Incarcerated (PI)
cross-linking between MC:
more robust catalysts
Properties
- stable for several months in air without sublimation
- mice experiments: no acute toxicity
[PI OsO4] for synthesis of 1mol scale of campothecin precursor
Chem. Rev. 2009, 594.
[PI Pd] catalyst
O
y
x
O
4
H
no solvent
120 oC, 2h
cross linking
z
[PI Pd]
[MC Pd]
O
filtration
washing
drying
O
Reduction with Hydrogen Gas
Ph
Me
[PI Pd] (5 mol%)
H2 (1 atm) Ph
O
THF, rt, 1h
O
Cross Coupling
B(OH)2
Br
+
MeO2C
Me
1st
2nd
85
80
[PI Pd] (x mol%)
P(oMeOPh)3
(x mol%)
yield (%)
3rd
4th
87
91
5th
90
MeO2C
K3PO4
H2O-toluene
x = 0.01: quant; x = 0.001: 54% (TON = 53600)
Other reactions with [PI Pd], other PI catalysts: Chem. Rev. 2009, 594.
and related references
RCS Adv. 2012, 7456.
Baran Group Meeting
[PI Pd] vs. [PMI Pd] in Heck Reaction
Nanoclusters in PI Catalysts
I
[PI Au] for Oxidation Using Molecular Oxygen
copolymer
NaBH4
AuClPPh3
Hai Dao
04/20/2013
Shu Kobayashi
+
CO2Et
K2CO3 (2 eq.), solvent
NMR, 120 oC, 24 h
[PI Pd] (hexane/THF): 52% (TON = 52300)
[PMI Pd] (MeOH/DCM): 83% (TON = 82500)
cross linking
[PI Au]
[MC Au]
formation of
gold nanocluster
OH
Ph
Me
[PI Au] (1 mol%), air
O
Ph
Me
K2CO3 (3 equiv), rt, PhCF3/H2O
5h, 88%
Angew. Chem. 2007, 4229.
[PI/CB Au]: incoporate carbon black (CB) into microencapsulated Au to
enhance stability of goldnanoclusters
PI Catalysts Variation: Polymer-Micelle Incarcerated (PMI)
PI catalysts
structure of metal clusters are
not well regulated
Synthesis of [PMI Pd]
PMI catalysts
control size of clusters through
formation of polymer micelles
during formation of MC
CO2Et
Pd cat. (0.001 mol%)
"Three-phase tests":
Ar
I
cleavage
Pd cat.
Heck-adducts
Heck conditions
Pd(PPh3)4: 48 %; Pd/C: 10%; [PMI Pd]: 2%
Pd polymer micelles = nano reactors
no or low level of active
species in solutions
J. Am. Chem. Soc. 2005, 2125.
Bimetallic Effect in PI catalysts
Bimetallic nanoclusters: (reactivity of nanoclusters can be tunned by
combination with other metals)
- "ligand effect": donating and accepting electron btw two metals
- "ensemble effect": independent activations of substrates
Roucoux, A; Patin, H. et al. Chem. Rev. 2002, 3757.
Chiral Rh/Ag Nanoparticles for Asymmetric 1,4 Additions:
O
iPr
+
Me
PI/CB cat. (0.75 mol% as Ph)
Ligand (1 mol%)
Ph
O
iPr
Me
*
toluene/H2O, 100 oC, 6 h
PhB(OH)2
[PI/CB Rh]: 18% (-ee) vs. [PI/CB Rh/Ag(1/3)] 77% (92% ee)
change in structure of
copolymers for
micellar formation
One-pot Reaction
PI/CB Au(0.5 mol%) PI/CB Rh/Ag (1.5 mol%)
OH
K2CO3 (0.5 eq)
Ligand (2 mol% )
Pr
Ph
toluene/H2O
O2, 60 oC, 16h
iPr
Ligand
PhB(OH)2 (2 eq)
Ar, 100 oC, 18h
OH
Ph
Pr *
O
Ph
88% (94% ee)
J. Am. Chem. Soc. 2012, 16963.
Application of PI Catalysts to Microchannel Reactor, Science 2004, 1305.
Baran Group Meeting
Shu Kobayashi
Part 5. Other Works
Microreactor: Science 2004, 1305.
Combinatorial Chemistry: Chem. Soc. Rev., 1999, 1.
Hai Dao
11/03/2012