Transcript Document 7397491

Synthesis and Characterization of Au
Nanoparticles-Supported N-Heterocyclic
Carbene Copper(I) Complex. The Catalytic
Application on Huisgen Cycloaddition
Reactions
學生：莊雲婷
指導教授：于淑君 博士
2010 /07 / 30
Department of Chemistry & Biochemistry
Chung Cheng University
1
Phosphine Ligand
 Phosphines are electronically and sterically tunable.
P
P(Bu)3
O
P O
O
P(OiPr)3
P
P(Me)3
P
P(o-tolyl)3
 Expensive.
 Air sensitive.
 P-C, P-OR cleavage under high temperature.
 Metal leaching.
 Chemical waste.
2
N-Heterocyclic Carbenes
[M]
 NHCs are stronger σ-donor and weaker π-acceptor than the most
electron rich phosphines.
 NHCs can be useful spectator ligands, because they are sterically
and electronically tunable.
 NHCs can promote a wide series of catalytic reactions.
 NHCs have advantages over phosphines and offer catalysts with
better air-stability.
3
N-Heterocyclic Carbenes as Ligands
- In the early 90's NHC were found to have bonding properties
similar to trialklyphosphanes and alkylphosphinates.
Herrmann, W. A.; Öfele, K; Elison, M.; Kühn, F. E.; Roesky, P. W. J. Organomet. Chem. 1994, 480, C7-C9.
- compatible with both high and low oxidation state metals
- examples:
N Me
Me N
OC
CO
OC W CO
CO
Cl
CHN
NHC
V
CHN
NHC
Cl
Me
N
N
Me
Cl
Cl
Cl Ti Cl
Me
N Me
N
Me
O
N
N
Re O Mes
Mes
O
Cl Ru
Ph
Me N
N Me
Cl
PCy3
- reaction employing NHC's as ligands:
Herrmann, W. Angew. Chem. Int. Ed. 2002, 41, 1290-1309.
4
The Catalytic Applications of CuI
CuCl, O2

NH4OH, EtOH
Carl Glaser. Berichte der deutschen chemischen Gesellschaft 1869. 2, 422–424.
 O-arylation of Phenols
 Sonogashira Reaction
 Kharasch-Sosnovsky Reaction (Allylic Oxidations of Olefins)
 S-arylation of Thiols
 1,3-dipolar cycloaddition
 N-arylation of Amines (Buchwald-Hartwig Reaction)
 Hydrosilylation of Ketones
 Substitution Reaction
 Heck reaction
 Epoxidation Reaction
 Oxidation of Alcohols
 Reductive Aldol Reaction
5
Drawbacks of Traditional
Copper-Mediated Reactions
 insoluble in organic solvents - heterogeneous
Girard, C. Org. Lett., 2006. 1689-1692
 harsh reaction conditions
- high temperatures around 200 °C
- strong bases required
- toxic solvent such as HMPA
- long reaction times
- the yields are often irreproducible
 structure not clear
6
Catalyst Supported onto Au NPs Surface
catalyst
Au NPs with
controllable solubility
Au NPs have been known not only to
possess solid surfaces resembling the
(1 1 1) surface of bulk gold but also to
behave like soluble molecules for their
dissolvability,
precipitability,
and
redissolvability.
soluble metal complex
functional groups
coordinationl ligands
spacer linker
7
Lin, Y.-Y; Tsai, S.-C.; Yu, S. J. J. Org. Chem. 2008, 73, 4920-4928.
Gold Nanoparticles Modified with Ionic Liquid
Cl
N
Cl
N (CH2)6 S
+
NaBH4
HAuCl4
N
N (CH2)6 SH Aun
2
Photographs of the obtained solutions of
the 1-modified gold NPs after addition of
(a) HCl (b) HBr (c) HBF4 (d) HI (e) HPF6.
Chujo.Y. J. Am. Chem. Soc. 2004, 126, 3026-3027
(a)
(e)
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Azide-Alkyne Huisgen Cycloaddition
 Rolf Huisgen was the first to understand this organic reaction at 1961.
Huisgen, R. .Angew. Chem. Int. Ed. 1961. 11. 633–645.
 1,3-Dipolar cycloaddition between azide and alkyne to give a 1,2,3-triazole
N N N R1
+
R2
N
N
N
R1
N
alkyne
1,4-disubstituted
triazoles
N
R1
+
R2
azide
N
R2
1,5-disubstituted
triazoles
 K. Barry Sharpless and co-workers defined it as “a set of powerful, highly
reliable, and selective reactions for the rapid synthesis of useful new compounds
and combinatorial libraries”
Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004-2021
9
Anke Cwiklicki, A. Arch. Pharm. Pharm. Med. Chem. 2004, 337, 156−163
First Metal Catalyzed Azide-Alkyne Cycloaddition
Copper
(i) 2 eq 2-Azido-2-methylpropionic acid, 50 eq DIPEA, 2 eq CuI.
(ii) 0.1 M NaOH (aq).
Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057-3064
Ruthenium
2 mol % cat.
Rt, 30 min
Yield = 63-97 %
Fokin, V. V.; Jia, G.; Lin, Z. J. Am. Chem. Soc. 2008. 130. 8923–8930
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Reported CuI Catalyzed AzideAlkyne Cycloaddition
 Reduction of CuII Salt
O
+
N
N
Sharpless, K. B. Angew. Chem. Int. Ed. 2002, 41, 2596-2599
CuSO4‧ 5H2O, 1 mol%
sodium ascorbate, 5 mol%
N
N
N
O
N
H2O/BuOH, 2:1, RT, 8h
TOF= 2.3 h-1
 Oxidation of Cu Metal
Alonso, F. Eur. J. Org. Chem. 2010, 1875-1884.
10 mol % Cu NPs
+
N
N
N
N3
THF, 65oC,10 min
TOF= 59 h-1
98 %
 Ligand Assisted CuI Salt
1 mol % N
+
N3
Fokin, V. V.Org. Lett. 2004, 6, 2853-2855
N Bn
N N
3
1 mol % Cu(CH3CN)4PF6
H2O/t-BuOH = 1:2, rt, 24h
N
N
N
84 %
TOF= 3.5 h-1
11
Reported CuI Catalyzed AzideAlkyne Cycloaddition
 NHC-CuI
Nolan, S. P. Chem. Eur. J. 2006, 12, 7558-7564.
0.8 mol % (SIMes)CuBr
N3
N
+
N
N
neat, rt, 20 min
TOF= 368 h-1
98 %
 Supported CuI Salt on Solid Phase
N
N3
N
+
N
Catalyst
Cu loading
(mol %)
Temp.
(oC)
Time
(hr)
Yield
(%)
TOF
(h-1)
ref
Cu(OH)x/TiO2
1.5
60
0.16
99a
396
Chem. Eur. J. 2009, 10464
CuNPs/AlO(OH)
3
rt
6
94b
5
J. Org. Lett. 2008. 497
CuI-Zeolite
10
rt
15
83c
0.6
J. Org. Lett. 2007, 883
SiO2-NHC-CuI
1
rt
0.5
93d
186
Tetrahedron, 2008, 10825
12
Reported Mechanism for CuI-Catalyzed
Azide-Alkyne Cycloaddition
13
Nolan, S. P. Angew. Chem. Int. Ed. 2008, 47, 8881 –8884
Motivation
 Using NHCs to replace phosphines in organomatallic
catalysis.
 Base on economic standpoint, copper metal is much more
Inexpensive than palladium catalyst .
- PdCl2 $4805.00(150g) ReagentPlus® (Aldrich)
- CuCl $206.00(100g) ReagentPlus® (Aldrich)
 Synthesis of NHC-Cu(I) complexes with well-defined
structures.
 Greener catalysis – microwave and solventless conditions.
 To design an easily recovered and effectively recycled
Au NPs supported copper(I) complex catalyst.
14
Preparation of CuI Complex Catalyst
N
I
Cu
N
CuI, t-BuONa
N
Br
65 oC, 12 h
yield = 95 %
N
N
N
THF reflux, 24h
yield = 96 %
Br
CuI(hmim)
(2)
(hmim)HBr
(1)
hmim = 1-hexyl-3-methylimidazolium
Preparation of (HS-hmim)HPF6
N
Br
1. CS(NH2)2, EtOH reflux, 16 h
2. NaOH, 20oC, 3 min
3. HCl, 20oC, 20 min
N
N
Br
o
DMF, 65 C, 16 h
yield = 95 %
N
Br
Yield = 70 %
Br
KPF6, H2O
N
N
SH
Br
N
o
0 C, 30 min
yield = 53 %
N
SH
PF6
(HS-hmim)HPF6
(3)
15
Synthesis of Octanethiol Protected Au NPs
[CH3(CH2)7]4N+Br-
SH
S
TOAB
SR
NaBH4
CHCl3, 1 h
CHCl3. 15 min
H2O, 8 min
HAuCl4 -4H2O
Au S
S
Au(SR)
(4)
TOAB = tetra-octyl ammonium bromide
SR = Octane thiol
Au(SR) size : 2.4  0.39 nm
16
Synthesis of Au NPs Modified with Ionic Liquid
N
S
Au S
S
N
SH
PF6
(3)
THF, 40 oC, 4 h
Au
S
S
S
PF6
N
Au(SR)
(4)
Au(SR)m(IL)n
(5)
N
N
N
PF6
IL = (S-hmim)(HPF6)
Au(SR)(IL) size : 2.04  0.7 nm
17
-CH3
H2
C
HS
CH3
HS-CH2-
CHCl3
S
S
Au
(4)
H2
C
CH3
C
H2
-CH3
CH3
CHCl3
SH
(3)
N
C
H2
N
PF6
HS-CH2DMSO
S
Au S
(5)
H2
C
CH3
DMSO
C
H2
N
N
PF6
-CH3
18
Design of Au(SR)(IL)(ILCu) (6)
N
N
SH
PF6
S
Au S
S
Au
S
S
S
N
N
PF6
N
N
PF6
Au
Cl
Cu
S
S
S
N
N
CuCI, t-BuONa
Solvent = CH3CN,
CuI, t-BuONa
Solvent = DMF
CH3CN,
THF
Cl
Cu
N
N
19
Synthesis of Au NPs Supported NHC-CuI Complex
Au
S
S
S
CuCl, t-BuONa
PF6
N
Au(SR)m(IL)n
(5)
Au
N
N
CH3CN, 60 oC, 24 h
Cl
Cu
S
S
S
N
N
Cl
Cu
N
PF6
Au(SR)x(IL)y(ILCu)z
(6)
N
N
ILCu = S-hmim-CuCl
Au(SR)(IL)(ILCu) size : 1.63  0.32 nm
20
1H
NMR Spectra of (hmim)HBr (1) & CuI(hmim) (2)
-CH3
Ha
H3C N
Hb
N
H2
C
Br
(hmim)HBr
(1)
Hb
H2O
-CH2-
Hb
Ha
#
DMSO
*
I
Cu
H3C N
Hb
N
Hb
-CH3
H2
C
CuI(hmim)
(2)
Hb
-CH2#
H2O
*
DMSO
21
1H
NMR Spectra of Au(SR)(IL) (5) &
Au(SR)(IL)(ILCuCl) (6)
CH3
Au
S
S
Au(SR)0.17(IL)1
(5)
Ha
H2
C
-CH3
#H O
2
*d-DMSO
Ha
N
N CH3
Hb
Hb
PF6
-CH2-
Hb
-CH3
CH3
Au
S
S
Au(SR)0.09(ILCu)1
(6)
H2
C
N
Hb
#H O
2
Cl
Cu
N CH3
*d-DMSO
-CH3
Hb
-CH2Hb
-CH3
22
13C
NMR Spectra of Au(SR)(IL) (5) &
Au(SR)(IL)(ILCuCl) (6)
*DMSO
Au
S
H
C
S
N
N
C C
PF6
H
H
Au(SR)0.17(IL)1
(5)
123.6 ppm
122.1 ppm
136.3 ppm
Au
S
S
Au(SR)0.09(ILCu)1
(6)
Cl
Cu
C
N
N
C C
H
H
*DMSO
123.3 ppm
121.9 ppm
182.6 ppm
23
IR Spectra of Ligand and NHC-CuI Series
160
(S-hmim)HPF6 (3)
2589
140
Au(SR)(IL) (5)
120
T (%)
100
Au(SR)(IL)(ILCu) (6) 1573
80
(hmim)HBr (1)
1636
60
20
0
4000
1169
1677
3500
3000
2500
1229
1575
CuI(hmim) (2)
40
1167
2000
1500
-1
Wavenumber (cm )
1218
1000
24
EDS of Au(SR)(IL)(ILCuCl) (6)
Au
S
Cl
S
Cu
N
N
Ni
Element
Weight%
Atomic%
C
25.56
72.89
Ni
25.13
14.67
Cu
10.60
5.71
Au
38.71
6.73
25
XPS of Au(SR)(IL)(ILCuCl) (6)
4f5/2
1200
4f7/2
1000
Intensity (counts/sec)
Au
Au
800
Au
83.7 eV
87.5 eV
600
83.8 eV
400
87.5 eV
200
0
92
90
88
86
84
82
80
78
Binding Energy(eV)
Brust, M. J. Chem. Soc. Chem. Commun. 1994, 801-802.
26
XPS of Au(SR)(IL)(ILCuCl) (6)
2p3/2
Cu
932.8
2p1/2
Intensity
952.6
965
960
955
950
945
940
Binding Energy (eV)
935
930
Binding Energy
Cu(2p1/2)
Cu(2p3/2)
CuClPPh3
953.2 eV
933.5 eV
CuCl(PPh2H)3
953.3 eV
933.4 eV
CuCl(PPh3)(o-phen)
952.4 eV
932.4 eV
Frost, D. C. Mol. Phys, 1972. 24. 861-877.
27
CuI(hmim) (2) Catalyzed Huisgen Cycloaddition
– Solvent Effect
Condition: Benzyl azide = 1 mmol, phenyl acetylene = 1.2 mmol. solvent = 0.25 mL, rt, 1 mol%
(hmim)CuI. The conversion were determined by 1H NMR
28
CuI(hmim) (2) Catalyzed Huisgen Cycloaddition
27 %
Condition: Benzyl azide = 1 mmol, phenyl acetylene = 1.2 mmol. solvent = 0.25 mL, rt, 0.05 mol%
(hmim)CuI. The conversion were determined by 1H NMR
TOF
(h-1)
333
2225
5062
29
Nolan, S. P. Angew. Chem. Int. Ed. 2008, 47, 8881 –8884
CuI(hmim) (2) Catalyzed Huisgen Cycloaddition
Condition: azide = 1 mmol, phenyl acetylene = 1.2 mmol. neat, rt, 1 mol% (hmim)CuI. The conversion
were determined by 1H NMR
30
CuI(hmim) (2) Catalyzed Huisgen Cycloaddition
Condition: azide = 1 mmol, 1-nonyne = 1.2 mmol. neat, rt, 1 mol% (hmim)CuI. The conversion were
determined by 1H NMR
31
CuI(hmim) (2) Catalyzed Huisgen Cycloaddition
32
Cycloaddition Reactivity of Various Substrates
 Alkyne:
>
pKa = 19
pKa = 25
 Azide:
N3
O2N
N3
≅
N3
>
Br
>
N3
>
N3
>
N3
>
N3
33
CuI Contents of Au(SR)x(LR)y(ILCu)z (6)
Determined by NMR Spectroscopy
CH3
Au
S
S
Cl
Cu
H
I
N
H3CO
H
N
Au(SR)0.13(ILCu)1
(6)
H
H
H
H
2H
2H
2H
3H
 ILCu : iodoanisole = (1-0.1648) : 0.1648
= ILCu : 2.245 x 10-6
ILCu = 1.137 x 10-5 mol
d6-DMSO
4-iodoanisole : 2.245 x
Au(SR)(ILCu) : 8 mg
10-6 mol
 ILCu : SR = (1-0.1648) : 0.1080
= 1:0.13
34
 Au(SR)x(LR)y(ILCu)z = AuSR0.13LR0Cu1
AuILCuCl (6) Catalyzed Huisgen Cycloaddition
Conversion were determined by 1H NMR. Reaction condition : 10 mg AuSR0.38LR0Cu1.
benzyl azide = 1.8 mmol. phenyl acetylene = 2.15 mmol. solvent = 0.4 mL
35
AuILCuCl (6) Catalyzed Huisgen Cycloaddition
Conversion were determined by 1H NMR.
36
Various Copper Salts and Their
Cycloaddition Reactivities
Conversion were determined by 1H NMR. Reaction condition : benzyl azide = 2.8 mmol.
phenyl acetylene = 3.4 mmol. solvent = 0.75 mL. a.1,4-product and 1,5-product is mixed.
Reactivity : NHC-CuI > NHC-CuCl
37
Competative Substrate Binding on Au
Surface v.s. Thiol Poisoning
Conversion were determined by 1H NMR. Reaction condition : 10 mg CuCl(hmim), benzyl azide =
2.8 mmol. phenyl acetylene = 3.4 mmol. CHCl3= 2 mL. (4) = 2.33x10-6 mol octanethiol / mg
Decrease reactivity : free octanethiol > Au NPs supported-octanethiol
38
The Surface Thiol Ratio on AuILCuCl v.s.
Catalytic Reactivity
Au(SR)x(LR)y(Cu)z
Conversion were determined by 1H NMR. Reaction condition : 1 mol% Cu of (6). benzyl azide =
1 eq. phenyl acetylene = 1.2 eq. solvent = 0.25 mL.
Increase (x+y)/z , decrease reactivity
39
Saturation of Au Surface with Alkyne
CuCl
40
Au
Microwave-Assisted (6) Catalyzed
Huisgen Cycloaddition
N3
microwave
thermal
N
1 mol % Au(SR)0.19(IL)0.57(ILCu)1 (6)
+
N
N
600 W
Solvent
Time (min)
Conversion
(%)
[Bmim][Br]
0.5
65
1.5
4
2
24
3
99
0.5
8
1
54
DMSO
CH3CN
Conditions: Benzyl azide (0.8 mmol), alkyne (0.96 mmol),
Solvent = 0.15 mL. Conversion detected by 1H NMR
41
Kappe, C. O. Angew. Chem. Int. Ed. 2004, 43, 6250-6284.
Microwave-Assisted (6) Catalyzed
Huisgen Cycloaddition
Conversion were determined by 1H NMR. Reaction condition : cat.(6) = 10 mg, azide = 1 eq.
phenyl acetylene = 1.2 eq. solvent = 2 drop [Bmim][PF6].
42
Conclusions
 We have successful synthesized Au NPs- supported
NHC-CuI complex (6) and characterized it by using
1H- and 13C-NMR, TEM, IR, EDS and XPS.
 We have successfully demonstrated the catalytic
activity of the CuI complex in both the molecular
and supported forms for the Huisgen cycloaddition.
 Further acceleration on the rate of the CuI catalyzed
Huisgen cycloaddition was achieved under
microwave irradiation conditions.
43