1. Gold Catalysis

2. Outline General properties of gold: - The element
- Facts and myths
Heterogeneous catalysis (briefly):
- Main characteristics
- Examples: ethyne hydrochlorination, oxidations, hydrogenation, …
Homogeneous catalysis
- Overview
- Gold as an oxidant
- Gold as an Lewis Acid
- C-H activation
- Alkyne activation
- Allene activation
- Asymmetric reaction
- Recent literature
Conclusion
Questions?

3. Gold: The Element 11

4. Gold: The Element
Name: from the Sanskrit word Jval and the Anglo-Saxon gold. Gold’s chemical symbol comes from the Latin word Aurum. Known for at least 5500 years.
Sources: generally in conjunction with silver, quartz (SiO2), calcite (CaCO3), lead, tellurium, zinc or copper. 2/3 of the world’s gold comes from South Africa. It is present in sea water: about 0.1 to 2 mg/ton, but no isolation method has been developed.
Characteristic: most malleable and ductile metal, good conductor of heat and electricity, not attacked by oxygen or sulfur. Reacts with halogens (e.g. aqua regia dissolved gold). Soft metal, so it is alloyed with others metals like Ag, Cu, Pt and Pd to increase the strength (e.g. application in jewelry).
Applications: the isotope Au-198 (half-life 2.7 days) used for treating cancer. AuNa3O6S4 (gold sodium thiosulfate) used for arthritis. HAuCl4 (chlorauric acid) used to preserve photographs by replacing the silver atoms.

5. c.f. Christopher’s presentation
Gold: The Element
Electron configuration: [Xe] 6s1 4f14 5d10
Oxidation States: from –I to III and +V
Most common Gold (I) and Gold (III) complex, both used in homogeneous catalysis.
Prices for 1g (STREM catalog ): Au Pt Pd Rh Ru
AuCl86$
PtCl 70$
PdCl2
38$
RhCl(PPh3) 42$
very expensive
AuBr3 55$
PtO2 76$
Pd(OAc)2
52$
RhCl3 136$
c.f. Christopher’s presentation
HAuCl440$
Pt 110$
Pd2(dba)366$
Rh(acac)2 134$
PPh3AuCl 125$ (Alfa Aesar)

6. Gold: Facts and Myths FALSE: TRUE:
Gold is chemically inert and uninteresting
Gold is expensive (cheaper than Platinum)
TRUE:
Gold is stable in the presence of oxygen and water
Gold can be used for heterogeneous and homogeneous catalysis
When is it convenient to use gold as a catalyst? (A. S.K. Hashmi Gold Bull. 2004, 51-65)
“The use of gold as a catalyst is desirable when it shows similar activity as for a more expensive catalyst or higher selectivity than a less expensive catalyst and when a new transformation is possible”.

7. Outline General properties of gold: - The element
- Facts and myths
Heterogeneous catalysis (briefly):
- Main characteristics
- Examples: ethyne hydrochlorination, oxidations, hydrogenation, …
Homogeneous catalysis
- Overview
- Gold as an oxidant
- Gold as an Lewis Acid
- C-H activation
- Alkyne activation
- Allene activation
- Asymmetric reaction
- Recent literature
Conclusion
Questions?

8. Heterogeneous Catalysis
Key Features:
Particle size (1 and 10 nm in diameter)
Nature of the support (transition metal oxide, carbon, zeolite)
Active Catalyst: supported small metallic gold particles
Advantages:
High catalytic activity (small amounts are necessary)
Mild conditions (low temperature, low pressure)
Good resistance to deactivation
INDUSTRIAL APPLICATIONS
G. J. Hutchings Catal. Today 2005, 55-61; C. W. Corti, R. J. Holliday, D. T. Thompson Catal. Today 2005,

9. Heterogeneous Catalysis
Ethyne (acetylene) Hydrochlorination
PVC market
G. J. Hutchings J. Catal. 1985, ; G. J. Hutchings Gold Bull. 1996, 123.
Advantages:
3x more reactive than the traditional HgCl2
catalyst recycling
2. CO Oxidation at Low Temperature
Industrial, environmental and domestic sectors
M. Haruta, T. Kobayashi, H. Sano, N. Yamada Chem. Lett. 4, 1987, 405.
Anhydrous conditions necessary
Not active at ambient temperature
Catalyst:
Hopcalyte (mixed oxide of Mn and Cu)
More active and stable
Activity at -70 ºC
Au/Fe2O3 or Co3O4

10. Heterogeneous Catalysis
3. Oxidations Mediated by O2
High temperatures are necessary ( ºC) and product mixtures are observed.
Catalyst:
1% Au/C (reagent/catalyst= 1000)
conversion: 96%
selectivity: 98%
1% Au/TiO2
conversion: 95%
selectivity: 98%
5% Pd or Pt/C
selectivity: 77%
1% Au/C
conversion: 22%
selectivity: 100%
1% Au/Al2O3
conversion: 100%
selectivity: 100%
5% Pd or Pt/C
no reaction
S. Biella, G.L. Castiglioni, C. Fumagalli, L. Prati, M. Rossi Catal. Today 2002,

11. Heterogeneous Catalysis
3. Oxidations Mediated by O2
1% Au/graphite
O2 3 atm, NaOH aq
60ºC, 3h
conversion: 56%
selectivity: 100%
5% Pt/C
55%
O2 6 atm, NaOH aq
60ºC, 3h
conversion: 88%
selectivity: 63%
23%
S. Carrettin, P. McMorn, C. Fumagalli, P. Johnston, K. Griffin, G. J. Hutchings Chem. Commun. 2002,

12. Heterogeneous Catalysis
4. Selective Hydrogenation (under H2 pressure)
Extended studies on the size particles, supports and synthesis technique on the selectivity.
P. Claus Appl. Catalysis A: General 2005,

13. Heterogeneous Catalysis
4. Selective Hydrogenation
Au/SiO2
Pt, Pd and Rh
S. Schimpf, M. Lucas, C. Mohr, U. Rodemerck, A. Bruckner, J. Radnik, H. Hofmeister, P. Claus Catal. Today 2002,

14. Heterogeneous Catalysis
5. Industrial Application: Commercial Uses (Patent)
C. W. Corti, R. J. Holliday, D. T. Thompson Appl. Catalysis A: General 2005,

15. Outline General properties of gold: - The element
- Facts and myths
Heterogeneous catalysis (briefly):
- Main characteristics
- Examples: ethyne hydrochlorination, oxidations, hydrogenation, …
Homogeneous catalysis
- Overview
- Gold as an oxidant
- Gold as an Lewis Acid
- C-H activation
- Alkyne activation
- Allene activation
- Asymmetric reaction
- Recent literature
Questions?

16. Homogeneous Catalysis
Key Features:
Soft transition metal, soft partners such as carbon are preferred.
Often reactions are faster than other transition metals. In some cases a completely new
product is formed.
Low propensity for β-H elimination.
Organogold intermediates undergo fast protodemetallation.
Cross-coupling chemistry seems difficult due to the easy reduction (difficult oxidation) of
gold.
It has been shown that often reactions are possible with both Au (I) and Au (III), so the
real catalytic species is not known. On the other hand, in some cases different products
are observed for the different oxidation states.
A. S.K. Hashmi Gold Bull. 2003, 3-9; A. S.K. Hashmi Gold Bull. 2004, 51-65; A. S.K. Hashmi Angew. Chem. Int. Ed. 2005, 44,
A. Arcadi, S. Di Giuseppe Curr. Org. Chem. 2004, 8, ; A. Hoffmann-Roder, N. Krause Org. Biol. Chem. 2005, 3,

17. Homogeneous Catalysis
Gold as an oxidant
1.1 Thioether Oxidation
F. Gasparrini, M. Giovannoli, D. Misiti, G. Natile, G. Palmieri Tetrahedron 1983, 39, and 1984, 40,
1.2 Oxidative Alkyne Coupling
F. Gasparrini, M. Giovannoli, D. Misiti, G. Natile, G. Palmieri, L. Maresca J. Am. Chem. Soc. 1993, 115,
1.3 Baeyer-Villiger Oxidation
J. Sundermeyer, C. Jost DE

18. Homogeneous Catalysis
2. Gold as a Lewis Acid
2.1 Michael Addition
S. Kobayashi, K. Kakumoto, M. Sugiura Org. Lett. 2002, 4,
2.2 Carbonyl-amine condensation
A. Arcadi, M. Chiarini, S. Di Giuseppe Green Chemistry 2003, 5,

19. Homogeneous Catalysis
2. Gold as a Lewis Acid (continue)
2.3 Friendländer Quinoline Synthesis
A. Arcadi, M. Chiarini, S. Di Giuseppe, F. Marinelli Synlett 2003,

20. Homogeneous Catalysis
2. Gold as a Lewis Acid (continue)
A. Arcadi, M. Chiarini, S. Di Giuseppe, F. Marinelli Synlett 2003,

21. Homogeneous Catalysis
3. C-H Activation
Hydroarylation of Alkynes
Y. Fuchita, Y. Utsunomiya, M. Yasutake J. Chem. Soc., Dalton Trans. 2001,
M. T. Reetz, K. Sommer Eur. J. Org. Chem. 2003,

22. Homogeneous Catalysis
3. C-H Activation
1M. T. Reetz, K. Sommer Eur. J. Org. Chem. 2003,
2Z. Shi, C. He J. Org. Chem. 2004, 69,
Proposed Mechanism:
M. T. Reetz, K. Sommer Eur. J. Org. Chem. 2003,

23. Homogeneous Catalysis
3. C-H Activation
Z. Shi, C. He J. Am. Chem. Soc. 2004, 126,
Z. Shi, C. He J. Org. Chem. 2004, 69,
X. Yao, C. -H. Li J. Am. Chem. Soc. 2004, 126,
Also applied to diene, triene and cyclic enol ethers!
Y. Luo, C. -H. Li Chem. Comm. 2004,
Li and Al. Org. Lett. 2005, 7,

24. Homogeneous Catalysis
4. Alkynes Activation
4.1 Nucleophilic Addition to Alkynes
O-Nucleophile
N-Nucleophile
Tetrahydropyridine
1Y. Fukuda, K, Utimoto J. Org. Chem. 1991, 56,
2J. H Teles, S. Brode, M. Chabanas Angew. Chem. Int. Ed. 1998, 37,
3Y. Fukuda, K, Utimoto Synthesis. 1991,

25. Homogeneous Catalysis
4. Alkyne Activation
4.1 Nucleophilic Addition to Alkynes
Pyrroles1
Indoles2
1A. Arcadi, S. Di Giuseppe, F. Marinelli, E. Rossi Adv. Syn. Catal. 2001, 5,
2A. Arcadi, G. Bianchi, F. Marinelli Synthesis 2004, 4,

26. Homogeneous Catalysis
4. Alkyne Activation
4.1 Nucleophilic Addition to Alkynes
Pyridines
G. Abbiati, A. Arcadi, G. Bianchi, S. Di Giuseppe, F. Marinelli, E. Rossi J. Org. Chem. 2003, 68,

27. Homogeneous Catalysis
4. Alkyne Activation
4.1 Nucleophilic Addition to Alkynes
Pyridines
NaAuCl4 2.5 %
EtOH reflux
6-endo-dig
46-98%
G. Abbiati, A. Arcadi, G. Bianchi, S. Di Giuseppe, F. Marinelli, E. Rossi J. Org. Chem. 2003, 68,

28. Homogeneous Catalysis
4. Alkyne Activation
4.2 Furan Isomerisation R R 3 4 R
Same conditions! R R
A. S. K. Hashmi, T. M. Frost, W. Bats J. Am. Chem. Soc. 2000, 122,

29. Homogeneous Catalysis
4. Alkyne Activation
4.2 Furan Isomerisation: Synthesis of Jungianol
75% 0% 0%
Jungianol 7%
68%
21%
A. S. K. Hashmi, T. L. Ding, W. Bats, P. Fischer, W. Frey Chem. Eur. J. 2003, 9,

30. Homogeneous Catalysis
4. Alkyne Activation
4.3 Benzoannulation
AuX3
Cu(OTf)2 1 3 11
AuX3
N. Asao, T. Nogami, S. Lee, Y. Yamamoto J. Am. Chem. Soc. 2003, 125,

31. Homogeneous Catalysis
4. Alkyne Activation
exo-dig and 5-endo-dig Carbocyclisation 1
5-exo-dig
5-exo-dig
93% 2 3 5 4
Conditions: 1% Au(PPh3)Cl, 1% AgOTf
CH2Cl2, r.t 5 min to 24 h
J. J. Kennedy-Smith, A. T. Staben, F. D. Toste J. Am. Chem. Soc. 2004, 126,

32. Homogeneous Catalysis
4. Alkyne Activation
exo-dig and 5-endo-dig Carbocyclisation
5-endo-dig 1 2 3 5 4
A. T. Staben, J. J. Kennedy-Smith, F. D. Toste Angew. Chem. Int. Ed. 2004, 43,

33. Homogeneous Catalysis
4. Alkyne Activation
4.5 Cycloisomerisation
C. Nieto-Oberhumber, M. Paz Munoz, E. Bunuel, C. Nevado, D. J. Cardenas, A. M. Echavarren Angew. Chem. Int. Ed , 43,

34. Homogeneous Catalysis
4. Alkyne Activation
4.5 Cycloisomerisation (continue)
PtCl2 shows broader scope
Au(I) vs. Au(III)
1M. Mendez, M. Paz Munoz, E. Bunuel, C. Nevado, D. J. Cardenas, A. M. Echavarren J. Am. Chem. Soc. 2001, 123,
2C. Nieto-Oberhumber, M. Paz Munoz, E. Bunuel, C. Nevado, D. J. Cardenas, A. M. Echavarren Angew. Chem. Int. Ed , 43,

35. Homogeneous Catalysis
4. Alkynes Activation
4.5 Cycloisomerisation (Nolan)
1P. De Frémont, N. M. Scott, E. D. Stevens, S. P. Nolan Orgaometallics. 2005, 24, S. P. Nolan and al. Chem. Commun. (ASAP).
3 S. P. Nolan and al. Angew. Chem. Int. Ed. (on press).

36. Homogeneous Catalysis
5. Allene Activation
5.1 Cycloisomerisation of α-hydroxyallenes1,2
Classical conditions: HCl(g) in CHCl3
or stoichiometric AgNO3
1A. Hoffmann-Roder, N. Krause Org. Lett. 2001, 3,
2N. Krause, A. Hoffmann-Roder, J. Canisius Synthesis 2002, 12,

37. Homogeneous Catalysis
5. Allene Activation
5.2 Cycloisomerisation of α-amino-1 and α-thio- allenes 2
3-pyrrolines
2,5-dihydrothiophenes
AuCl (5%)
88%
1N. Morita, N. Krause Org. Lett. 2004, 6,
2N. Morita, N. Krause Anew. Chem. Int. Ed. 2006, 45,

38. Homogeneous Catalysis
5. Allene Activation
Proposed Mechanism:
In the case of α-thioallenes more investigation are necessary to established the catalytic species!

39. Homogeneous Catalysis
6. Asymmetric Reactions
6.1 Asymmetric Aldol Condensation
Proposed transition state:
I. Yoshihiko, M. Sawamura, T. Hayashi J. Am. Chem. Soc. 1986, 108,

40. Homogeneous Catalysis
6. Asymmetric Reactions
6.1 Asymmetric Aldol Condensation
balanol
90%
dr 19:1%
ee > 99%
threo-3-hydroxylysine
P. F. Hughes, S. H. Smith, J. T. Olson J. Org. Chem. 1994, 58,

41. Homogeneous Catalysis
6. Asymmetric Reactions
6.2 Asymmetric Cycloisomerisation
5% PtCl2, MeOH, (S)-TolBINAP, 80ºC
94%, 48% ee (-)
M.P. Munoz, J. Adrio, J.C. Carrettero, A.M. Echavarren Organometallics 2005, 24,

42. Homogeneous Catalysis
6. Asymmetric Reactions
6.3 Asymmetric Hydrogenation
C. Gonzalez-Arellano, A. Corma, M. Iglesias, F. Sanchez Chem. Commun. 2005,

43. Homogeneous Catalysis
Recent Literature: Nucleophilic Attack to Unactivated Alkenes 1 2 3
1C.-G. Yang, C. He J. Am. Chem. Soc. 2005, 127,
2J. Zhang, C.-G. Yang, C. He J. Am. Chem. Soc. 2006, 128,
3C. Brouver, C. He Angew. Chem. Int. Ed. 2006, 45,

44. Conclusion Au (I) or Au (III)? Au(PEt3)Cl X X X= Cl, Br, I R R X R
Toluene, 5 min to 3 days 1 2 3
AuCl3
A. W. Someck, M. Rubina, V. Gevorgyan J. Am. Chem. Soc. 2005, 127,

45. What is the Gold’s reagent?
Questions?
[[[(Dimethylammino)methylene]amino]-methylene]dimethylammonium Chloride1
It is a brown solid and it is a β-dimethylaminomethylenating agent for ketones and amines2
2J. T. Gupton, C. Colon, C. R. Harrison, M. J. Lizzi, D. E. Polk J. Org. Chem. 1980, 45,
1Encyclopedia of Reagents for Organic Synthesis (Ed L.A. Paquette) Vol3, 1995, 2014.
What is the Gold’s reagent?

69. However, Parravano’s group reported the investigation of the activity of gold in oxygen/hydrogen- transfer reactions, and the reduction of NO by dihydrogen, but these studies remained isolated.
Therefore, the discovery by Haruta et al., reported in 1989, that AuNPs supported on Co3O4 ,Fe2O3,orTiO2were highly active catalysts, under high dispersion, for CO and H2 oxidation,NO reduction, water-gas shift reaction, CO2 hydrogenation, and catalytic combustion of methanol was a surprise, and was considered important by the chemical community. Catalysis with AuNPs, in particular the very active oxide-supported ones, is now an expanding area

70. per
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