1. Department of Chemistry & Biochemistry Chung Cheng University
The Study of Catalytic Application of N-Heterocyclic Carbene Copper(I) Complex in Both Molecular and Supported Forms on Huisgen Cycloaddition Reactions.
學生：莊雲婷
指導教授：于淑君　博士
2010 / 05 / 03
Department of Chemistry & Biochemistry
Chung Cheng University

2. Phosphine Ligand Phosphines are electronically and sterically tunable.
Expensive.
Air sensitive.
Metal leaching.
Chemical waste.

3. N-Heterocyclic Carbenes
[M]
NHCs are stronger σ-donor and weaker π-acceptor than the most
electron rich phosphine,
NHCs can be useful spectator ligands, because they are sterically
and electronically tunable.
NHCs can promote a wide series of catalytic reactions like phosphine.
NHCs have advantages over phosphines andoffer 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
- toxic solvent such as HMPA
- sensitive to functional groups on aryl halides
- 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. Motivation Using NHCs ligand to replace phosphine ligand in
organomatallic catalysis.
Base on economic standpoint, copper metal is cheaper
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.
Easily recovered and effectively recycled catalyst
NHC-Cu(I) complexs by immobilization onto Au NPs.

9. The First Isolable Carbene-CuI Complexes
Arduengo, A. J., III; Dias, H. V. R.; Calabrese, J. C.; Davidson, F. Organometallics 1993, 12,

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

11. Synthesis of 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,

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

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

14. -CH3
HS-CH2-
CHCl3
-CH3
CHCl3
HS-CH2-
DMSO
DMSO
-CH3

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

16. 1H NMR Spectra of (hmim)HBr (1) & (hmim)CuI (2)
-CH2- Hb Ha
-CH3 * #
H2O
DMSO

17. 1H NMR Spectra of Au(SR)(IL) (5) & Au(SR)(IL)(ILCu) (6)
*d-DMSO
#H2O Hb Ha
-CH2-
-CH3

18. 13C NMR Spectra of Au(SR)(IL) (5) & Au(SR)(IL)(ILCu) (6)
136.3 ppm
182.6 ppm
*DMSO
123.3 ppm
121.9 ppm
123.6 ppm
122.1 ppm

19. 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

20. EDS and XPS of Au(SR)(IL)(ILCu) (6)
Galtayries, A.; Bonnelle, J. -P. Surf. Interface Anal. 1995, 23, 171.
2p3/2
933
932.8
2p1/2
Tubaro, C.; Tetrahedron

21. Azide-Alkyne Huisgen Cycloaddition
The is a 1,3-dipolar cycloaddition between azide alkyne to give a 1,2,3-triazole
Rolf Huisgen was the first to understand this organic reaction at 1961.
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

22. Azide-Alkyne Huisgen Cycloaddition
(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,
2 mol % cat.
Rt, 30 min
Yield = %
Fokin, V. V.; Jia, G.; Lin, Z. J. Am. Chem. Soc –8930

23. Huisgen Cycloaddition
Reported NHC-CuI Catalytic
Huisgen Cycloaddition
TOF(h-1)
333
2225
5062
2022
180 66
389
37.5
394
[a] The conversion (determined by GC) is an average of the values for at least two independent experiments.
Nolan, S. P. Angew. Chem. Int. Ed. 2008, 47, 8881 –8884

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

25. (Hmim)CuI (2) Catalysis 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 is determined by 1H NMR

26. (Hmim)CuI (2) Catalysis Huisgen Cycloaddition
Condition: Benzyl azide = 1 mmol, phenyl acetylene = 1.2 mmol. solvent = 0.25 mL, RT, 0.05 mol% (hmim)CuI. The conversion is determined by 1H NMR
TOF
(h-1)
333
2225
5062
Nolan, S. P. Angew. Chem. Int. Ed. 2008, 47, 8881 –8884

27. (Hmim)CuI (2) Catalysis Huisgen Cycloaddition
Condition: azide = 1 mmol, phenyl acetylene = 1.2 mmol. neat, RT, 1 mol% (hmim)CuI. The conversion is determined by 1H NMR

28. (Hmim)CuI (2) Catalysis Huisgen Cycloaddition
Condition: azide = 1 mmol, 1-nonyne = 1.2 mmol. neat, RT, 1 mol% (hmim)CuI. The conversion is determined by 1H NMR

29. (Hmim)CuI (2) Catalysis Huisgen Cycloaddition
Condition: azide = 1 mmol, alkyne = 1.2 mmol. CH3CN = 0.25 mL, RT, 1 mol% (hmim)CuI. The conversion is determined by 1H NMR

30. N-Heterocyclic Carbenes CuI Supported on SiO2
TOF(h-1)=186
1.Structurally undefined
2.Quantitative
NHC-CuI by ICP-Mass
Cycle
Yield(%)b 1 93 6 92 2 7 90 3 91 8 4 9 88 5 89 10 87
Conditions: organic azide (1 mmol), alkyne (1 mmol),
SiO2–NHC–Cu(I) (1 mol %). B Isolated yields.C At 80 oC for 24 h.
Wang, L. Tetrahedron –10830

31. Determine CuI contents of Au(SR)(IL)(ILCu) (6)2H 2H 2H 3H
d6-DMSO
ILCu : iodoanisole = ( ) : = Cu : x 10-6
Cu = x mol
ILCu : SR = : = 1:0.13
4-iodoanisole
Au(SR)(ILCu) 8 mg

32. NHC-CuI Catalysis Huisgen Cycloaddition
Condition: Benzyl azide = 2 mmol, phenyl acetylene = 2.4 mmol. solvent = 0.5 mL. Yield determined by 1H NMR. (a) conversion is traced. (b) conversion is detected after reaction quenched. (c) 20 hr. (d) 16 hr

33. Using Microwave System to Catalysis 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,

34. Conclusions We have successful synthesis Complex 6 ,
and characterized by 1H- and 13C-NMR, TEM,
IR, EDS and XPS.
We have successfully demonstrated the
catalytic activity of the CuI complex for the
Huisgen cycloaddition.
In the future, we would try to use Au-NHC-CuI
for the recycling test on Huisgen cycloaddition.

35. Mechanism for Ru catalysis click reaction
2 mol % cat.
Rt, 30 min
80 %
Fokin, V. V.; Jia, G.; Lin, Z. J. Am. Chem. Soc –8930

36. 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

37. shake-up Self-Assembled Monolayers of Alkanethiols on Copper Surfaces
Sung, M. M.; Kim, Y.Bull. Korean Chem. Soc. 2001, Vol. 22, No. 7

38. (CO) of LNi(CO)3
Corn angle ()