1. Department of Chemistry & Biochemistry Chung Cheng University
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

2. Phosphine Ligand Phosphines are electronically and sterically tunable.
Expensive.
Air sensitive.
P-C, P-OR cleavage under high temperature.
Metal leaching.
Chemical waste.

3. 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.

4. N-Heterocyclic Carbenes as Ligands
- In the early 90's NHC were found to have bonding properties similar to trialklyphosphanes and alkylphosphinates.
- compatible with both high and low oxidation state metals
- examples:
- reaction employing NHC's as ligands:
Herrmann, W. A.; Öfele, K; Elison, M.; Kühn, F. E.; Roesky, P. W. J. Organomet. Chem. 1994, 480, C7-C9.
Herrmann, W. Angew. Chem. Int. Ed. 2002, 41,

5. The Catalytic Applications of CuI
O-arylation of Phenols
Kharasch-Sosnovsky Reaction (Allylic Oxidations of Olefins)
S-arylation of Thiols
N-arylation of Amines (Buchwald-Hartwig Reaction)
Hydrosilylation of Ketones
Heck reaction
Oxidation of Alcohols
Carl Glaser. Berichte der deutschen chemischen Gesellschaft , 422–424.
Sonogashira Reaction
1,3-dipolar cycloaddition
Substitution Reaction
Epoxidation Reaction
Reductive Aldol Reaction

6. Drawbacks of Traditional Copper-Mediated Reactions
insoluble in organic solvents - heterogeneous
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
Girard, C. Org. Lett.,

7. Catalyst Supported onto Au NPs Surface controllable solubility
soluble metal complex
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.
functional groups
coordinationl ligands
spacer linker
Lin, Y.-Y; Tsai, S.-C.; Yu, S. J. J. Org. Chem. 2008, 73,

8. Gold Nanoparticles Modified with Ionic Liquid
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,

9. Azide-Alkyne Huisgen Cycloaddition
Rolf Huisgen was the first to understand this organic reaction at 1961.
1,3-Dipolar cycloaddition between azide and alkyne to give a 1,2,3-triazole
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”
Huisgen, R. .Angew. Chem. Int. Ed –645.
Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40,
Anke Cwiklicki, A. Arch. Pharm. Pharm. Med. Chem. 2004, 337, 156−163

10. 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,
Ruthenium
2 mol % cat.
Rt, 30 min
Yield = %
Fokin, V. V.; Jia, G.; Lin, Z. J. Am. Chem. Soc –8930

11. Reported CuI Catalyzed Azide-Alkyne Cycloaddition
Reduction of CuII Salt
Oxidation of Cu Metal
Ligand Assisted CuI Salt
Sharpless, K. B. Angew. Chem. Int. Ed. 2002, 41,
TOF= 2.3 h-1
Alonso, F. Eur. J. Org. Chem. 2010,
TOF= 59 h-1
Fokin, V. V.Org. Lett. 2004, 6,
TOF= 3.5 h-1

12. Reported CuI Catalyzed Azide-Alkyne Cycloaddition
NHC-CuI
Supported CuI Salt on Solid Phase
Nolan, S. P. Chem. Eur. J. 2006, 12,
TOF= 368 h-1
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
CuI-Zeolite 10 15
83c
0.6
J. Org. Lett. 2007, 883
SiO2-NHC-CuI 1
0.5
93d
186
Tetrahedron, 2008, 10825

13. Reported Mechanism for CuI-Catalyzed Azide-Alkyne Cycloaddition機制
Nolan, S. P. Angew. Chem. Int. Ed. 2008, 47, 8881 –8884

14. Motivation Using NHCs to replace phosphines in organomatallic
catalysis.
Base on economic standpoint, copper metal is much more
Inexpensive than palladium catalyst .
- PdCl2 $ (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.

15. Preparation of CuI Complex Catalyst Preparation of (HS-hmim)HPF6
hmim = 1-hexyl-3-methylimidazolium
Preparation of (HS-hmim)HPF6

16. Synthesis of Octanethiol Protected Au NPs
TOAB = tetra-octyl ammonium bromide
SR = Octane thiol
Au(SR) size : 2.4  0.39 nm

17. Synthesis of Au NPs Modified with Ionic Liquid
IL = (S-hmim)(HPF6)
Au(SR)(IL) size : 2.04  0.7 nm

18. -CH3
HS-CH2-
CHCl3
-CH3
CHCl3
HS-CH2-
DMSO
DMSO
-CH3

19. Design of Au(SR)(IL)(ILCu) (6)

20. Synthesis of Au NPs Supported NHC-CuI Complex
ILCu = S-hmim-CuCl
Au(SR)(IL)(ILCu) size : 1.63  0.32 nm

21. 1H NMR Spectra of (hmim)HBr (1) & CuI(hmim) (2)
-CH2- Hb Ha
-CH3 * #
H2O
DMSO

22. 1H NMR Spectra of Au(SR)(IL) (5) & Au(SR)(IL)(ILCuCl) (6)
*d-DMSO
#H2O Hb Ha
-CH2-
-CH3

23. 13C NMR Spectra of Au(SR)(IL) (5) & Au(SR)(IL)(ILCuCl) (6)
136.3 ppm
182.6 ppm
*DMSO
123.3 ppm
121.9 ppm
123.6 ppm
122.1 ppm

24. IR Spectra of Ligand and NHC-CuI Series
(S-hmim)HPF6 (3)
2589
Au(SR)(IL) (5)
Au(SR)(IL)(ILCu) (6)
1573
1167
1636
1229
(hmim)HBr (1)
1575
CuI(hmim) (2)
1169
1677
1218

25. EDS of Au(SR)(IL)(ILCuCl) (6)
Element
Weight%
Atomic% C
25.56
72.89 Ni
25.13
14.67 Cu
10.60
5.71 Au
38.71
6.73

26. XPS of Au(SR)(IL)(ILCuCl) (6)
87.5 eV
4f5/2
4f7/2
83.7 eV Au
83.8 eV
87.5 eV
Brust, M. J. Chem. Soc. Chem. Commun. 1994,

27. XPS of Au(SR)(IL)(ILCuCl) (6)
952.6
2p3/2
2p1/2 Cu
932.8
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,

28. 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

29. 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
Nolan, S. P. Angew. Chem. Int. Ed. 2008, 47, 8881 –8884

30. 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

31. 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

32. CuI(hmim) (2) Catalyzed Huisgen Cycloaddition

33. Cycloaddition Reactivity of Various Substrates
Alkyne:
Azide:
>
pKa = 19
pKa = 25 ≅
>
>
>
>
>

34. CuI Contents of Au(SR)x(LR)y(ILCu)z (6) Determined by NMR Spectroscopy2H 2H 2H 3H
ILCu : iodoanisole = ( ) :
= ILCu : x 10-6
ILCu = x mol
ILCu : SR = ( ) :
= 1:0.13
Au(SR)x(LR)y(ILCu)z = AuSR0.13LR0Cu1
d6-DMSO
4-iodoanisole : x 10-6 mol
Au(SR)(ILCu) : 8 mg

35. 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

36. AuILCuCl (6) Catalyzed Huisgen Cycloaddition
Conversion were determined by 1H NMR.

37. 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

38. 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

39. 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

40. Saturation of Au Surface with Alkyne
CuCl Au

41. Microwave-Assisted (6) Catalyzed Huisgen Cycloaddition
thermal
Solvent
Time (min)
Conversion (%)
[Bmim][Br]
0.5 65
DMSO
1.5 4 2 24 3 99
CH3CN 8 1 54
Conditions: Benzyl azide (0.8 mmol), alkyne (0.96 mmol), Solvent = 0.15 mL. Conversion detected by 1H NMR
Kappe, C. O. Angew. Chem. Int. Ed. 2004, 43,

42. 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].

43. 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.

44. Mechanism for Ru Catalyzed Click Reaction
2 mol % cat.
Rt, 30 min
80 %
Fokin, V. V.; Jia, G.; Lin, Z. J. Am. Chem. Soc –8930

45. Yamamoto, Y. Tetrahedron. Letters. 2008, 49, 2824-2827

46. Yamamoto, Y. Tetrahedron. Letters. 2008, 49, 2824-2827

47. DFT calculated barrier of Step A) 23.7 kcal/mol Step B) 0.7 kcal/mol
Step C) kcal/mol
Fokin, V. V. J. Am. Chem. Soc. 2005, 127,

48. NMR Characterization of Octanethiol-Protected Au NPs
The 1H-NMR spectra of (a) free octanethiol,
(b) Au:C8=1:5,(c) Au:C8=2:1, and (d) Au:C8=5:1.
The 13C-NMR spectra of (a) free octanethiol, (b) Au:C8=1:5,(c) Au:C8=2:1, and (d) Au:C8=5:1.
G.C. Lica et al. Journal of Electroanalytical Chemistry

49. (CO) of LNi(CO)3
Corn angle ()