1. 1 Gold Catalysis Federica Stazi Ph.D. Literature Meeting Montréal, 11 th April 2006

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

3. 3 Gold: The Element 11

4. 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 (SiO 2 ), calcite (CaCO 3 ), 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. AuNa 3 O 6 S 4 (gold sodium thiosulfate) used for arthritis. HAuCl 4 (chlorauric acid) used to preserve photographs by replacing the silver atoms.

5. 5 Gold: The Element Electron configuration: [Xe] 6s 1 4f 14 5d 10 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 2004-06): AuPdPtRhRu AuCl 86$ AuBr 3 55$ HAuCl 4 40$ PtCl 70$ PtO 2 76$ Pt 110$ PdCl 2 38$ Pd(OAc) 2 52$ Pd 2 (dba) 3 66$ RhCl(PPh 3 ) 42$ RhCl 3 136$ Rh(acac) 2 134$ very expensive c.f. Christopher’s presentation PPh 3 AuCl 125$ (Alfa Aesar)

6. 6 Gold: Facts and Myths FALSE: 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 “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”. When is it convenient to use gold as a catalyst? (A. S.K. Hashmi Gold Bull. 2004, 51-65)

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

8. 8 Heterogeneous 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, 253-261.

9. 9 Heterogeneous Catalysis 1.Ethyne (acetylene) Hydrochlorination G. J. Hutchings J. Catal. 1985, 292-295; G. J. Hutchings Gold Bull. 1996, 123. PVC market Advantages: 3x more reactive than the traditional HgCl 2 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. Catalyst: Hopcalyte (mixed oxide of Mn and Cu) Anhydrous conditions necessary Not active at ambient temperature Au/Fe 2 O 3 or Co 3 O 4 More active and stable Activity at -70 ºC

10. 10 Heterogeneous Catalysis 3. Oxidations Mediated by O 2 High temperatures are necessary (270 - 720 ºC) and product mixtures are observed. Catalyst: 1% Au/C (reagent/catalyst= 1000) conversion: 96% selectivity: 98% 1% Au/TiO 2 conversion: 95%selectivity: 98% 5% Pd or Pt/Cselectivity: 77% 1% Au/Cconversion: 22%selectivity: 100% 1% Au/Al 2 O 3 conversion: 100%selectivity: 100% 5% Pd or Pt/Cno reaction S. Biella, G.L. Castiglioni, C. Fumagalli, L. Prati, M. Rossi Catal. Today 2002, 43-49.

11. 11 Heterogeneous Catalysis 3. Oxidations Mediated by O 2 S. Carrettin, P. McMorn, C. Fumagalli, P. Johnston, K. Griffin, G. J. Hutchings Chem. Commun. 2002, 696-697. 1% Au/graphite conversion: 56% selectivity: 100% O 2 3 atm, NaOH aq 60ºC, 3h 5% Pt/C conversion: 88% 55% 23% O 2 6 atm, NaOH aq 60ºC, 3h selectivity: 63%

12. 12 Heterogeneous Catalysis 4. Selective Hydrogenation (under H 2 pressure) P. Claus Appl. Catalysis A: General 2005, 222-229. Extended studies on the size particles, supports and synthesis technique on the selectivity.

13. 13 Heterogeneous Catalysis 4. Selective Hydrogenation S. Schimpf, M. Lucas, C. Mohr, U. Rodemerck, A. Bruckner, J. Radnik, H. Hofmeister, P. Claus Catal. Today 2002, 63-78. Au/SiO 2 Pt, Pd and Rh

14. 14 Heterogeneous Catalysis 5. Industrial Application: Commercial Uses (Patent) C. W. Corti, R. J. Holliday, D. T. Thompson Appl. Catalysis A: General 2005, 253-261.

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

16. 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. 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, 6990-6993. A. Arcadi, S. Di Giuseppe Curr. Org. Chem. 2004, 8, 795-812; A. Hoffmann-Roder, N. Krause Org. Biol. Chem. 2005, 3, 387-391. Low propensity for β-H elimination.

17. 17 Homogeneous Catalysis 1.Gold as an oxidant F. Gasparrini, M. Giovannoli, D. Misiti, G. Natile, G. Palmieri Tetrahedron 1983, 39, 3181-3184 and 1984, 40, 165-170. F. Gasparrini, M. Giovannoli, D. Misiti, G. Natile, G. Palmieri, L. Maresca J. Am. Chem. Soc. 1993, 115, 4401-4402. J. Sundermeyer, C. Jost DE 10041510 1999. 1.1 Thioether Oxidation 1.2 Oxidative Alkyne Coupling 1.3 Baeyer-Villiger Oxidation

18. 18 Homogeneous Catalysis 2. Gold as a Lewis Acid S. Kobayashi, K. Kakumoto, M. Sugiura Org. Lett. 2002, 4, 1319-1320. A. Arcadi, M. Chiarini, S. Di Giuseppe Green Chemistry 2003, 5, 64-67. 2.1 Michael Addition 2.2 Carbonyl-amine condensation

19. 19 Homogeneous Catalysis 2. Gold as a Lewis Acid (continue) A. Arcadi, M. Chiarini, S. Di Giuseppe, F. Marinelli Synlett 2003, 203-206. 2.3 Friendländer Quinoline Synthesis

20. 20 Homogeneous Catalysis 2. Gold as a Lewis Acid (continue) A. Arcadi, M. Chiarini, S. Di Giuseppe, F. Marinelli Synlett 2003, 203-206.

21. 21 Homogeneous Catalysis 3. C-H Activation Y. Fuchita, Y. Utsunomiya, M. Yasutake J. Chem. Soc., Dalton Trans. 2001, 2330-2334. Hydroarylation of Alkynes M. T. Reetz, K. Sommer Eur. J. Org. Chem. 2003, 3485-3496.

22. 22 Homogeneous Catalysis 3. C-H Activation 2 Z. Shi, C. He J. Org. Chem. 2004, 69, 3669-3671. Proposed Mechanism: 1 M. T. Reetz, K. Sommer Eur. J. Org. Chem. 2003, 3485-3496. M. T. Reetz, K. Sommer Eur. J. Org. Chem. 2003, 3485-3496.

23. 23 Homogeneous Catalysis 3. C-H Activation Z. Shi, C. He J. Org. Chem. 2004, 69, 3669-3671. Z. Shi, C. He J. Am. Chem. Soc. 2004, 126, 5964-5965. Y. Luo, C. -H. Li Chem. Comm. 2004, 1930-1931. X. Yao, C. -H. Li J. Am. Chem. Soc. 2004, 126, 6884-6885. Also applied to diene, triene and cyclic enol ethers! Li and Al. Org. Lett. 2005, 7, 673-675.

24. 24 Homogeneous Catalysis 4. Alkynes Activation 4.1 Nucleophilic Addition to Alkynes 1 Y. Fukuda, K, Utimoto J. Org. Chem. 1991, 56, 3729-3731. 2 J. H Teles, S. Brode, M. Chabanas Angew. Chem. Int. Ed. 1998, 37, 1415-1418. O-Nucleophile N-Nucleophile 3 Y. Fukuda, K, Utimoto Synthesis. 1991, 975-978. Tetrahydropyridine

25. 25 Homogeneous Catalysis 4. Alkyne Activation 4.1 Nucleophilic Addition to Alkynes 2 A. Arcadi, G. Bianchi, F. Marinelli Synthesis 2004, 4, 610-618. Pyrroles 1 1 A. Arcadi, S. Di Giuseppe, F. Marinelli, E. Rossi Adv. Syn. Catal. 2001, 5, 343-6346. Indoles 2

26. 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, 6959-6966.

27. 27 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, 6959-6966. NaAuCl 4 2.5 % EtOH reflux 46-98% 6-endo-dig

28. 28 Homogeneous Catalysis 4. Alkyne Activation A. S. K. Hashmi, T. M. Frost, W. Bats J. Am. Chem. Soc. 2000, 122, 11553-11554. 4.2 Furan Isomerisation R R R 34 Same conditions! R R

29. 29 Homogeneous Catalysis 4. Alkyne Activation A. S. K. Hashmi, T. L. Ding, W. Bats, P. Fischer, W. Frey Chem. Eur. J. 2003, 9, 4339-4345. 4.2 Furan Isomerisation: Synthesis of Jungianol 75%0% 68%21%7% Jungianol

30. 30 Homogeneous Catalysis 4. Alkyne Activation N. Asao, T. Nogami, S. Lee, Y. Yamamoto J. Am. Chem. Soc. 2003, 125, 10921-10925. 4.3 Benzoannulation AuX 3 Cu(OTf) 2 AuX 3 13 11

31. 31 Homogeneous Catalysis 4. Alkyne Activation 4.4 5-exo-dig and 5-endo-dig Carbocyclisation Conditions: 1% Au(PPh 3 )Cl, 1% AgOTf CH 2 Cl 2, r.t 5 min to 24 h J. J. Kennedy-Smith, A. T. Staben, F. D. Toste J. Am. Chem. Soc. 2004, 126, 4526-4527. 1 2 3 4 5 5-exo-dig 93%5-exo-dig

32. 32 Homogeneous Catalysis 4. Alkyne Activation 4.4 5-exo-dig and 5-endo-dig Carbocyclisation A. T. Staben, J. J. Kennedy-Smith, F. D. Toste Angew. Chem. Int. Ed. 2004, 43, 5350-5352. 1 2 3 4 5 5-endo-dig

33. 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. 2004, 43, 2402-2406.

34. 34 Homogeneous Catalysis 4. Alkyne Activation 4.5 Cycloisomerisation (continue) 2 C. Nieto-Oberhumber, M. Paz Munoz, E. Bunuel, C. Nevado, D. J. Cardenas, A. M. Echavarren Angew. Chem. Int. Ed. 2004, 43, 2402-2406. 1 M. Mendez, M. Paz Munoz, E. Bunuel, C. Nevado, D. J. Cardenas, A. M. Echavarren J. Am. Chem. Soc. 2001, 123, 10510-10520. Au(I) vs. Au(III) PtCl 2 shows broader scope

35. 35 Homogeneous Catalysis 4. Alkynes Activation 4.5 Cycloisomerisation (Nolan) 1 P. De Frémont, N. M. Scott, E. D. Stevens, S. P. Nolan Orgaometallics. 2005, 24, 2411-2418. 2 S. P. Nolan and al. Chem. Commun. (ASAP). 3 S. P. Nolan and al. Angew. Chem. Int. Ed. (on press).

36. 36 Homogeneous Catalysis 5. Allene Activation 5.1 Cycloisomerisation of α-hydroxyallenes 1,2 1 A. Hoffmann-Roder, N. Krause Org. Lett. 2001, 3, 2537-2538. 2 N. Krause, A. Hoffmann-Roder, J. Canisius Synthesis 2002, 12, 1759-1774. Classical conditions: HCl(g) in CHCl 3 or stoichiometric AgNO 3

37. 37 Homogeneous Catalysis 5. Allene Activation 5.2 Cycloisomerisation of α-amino- 1 and α-thio- allenes 2 1 N. Morita, N. Krause Org. Lett. 2004, 6, 4121-2123. 3-pyrrolines 2,5-dihydrothiophenes 2 N. Morita, N. Krause Anew. Chem. Int. Ed. 2006, 45, 1897-1899. AuCl (5%) 88%

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

39. 39 Homogeneous Catalysis 6. Asymmetric Reactions I. Yoshihiko, M. Sawamura, T. Hayashi J. Am. Chem. Soc. 1986, 108, 6405-6406. 6.1 Asymmetric Aldol Condensation Proposed transition state:

40. 40 Homogeneous Catalysis 6. Asymmetric Reactions P. F. Hughes, S. H. Smith, J. T. Olson J. Org. Chem. 1994, 58, 5799-5802. 6.1 Asymmetric Aldol Condensation threo-3-hydroxylysine balanol 90% dr 19:1% ee > 99%

41. 41 Homogeneous Catalysis 6. Asymmetric Reactions M.P. Munoz, J. Adrio, J.C. Carrettero, A.M. Echavarren Organometallics 2005, 24, 1293-1300. 6.2 Asymmetric Cycloisomerisation 5% PtCl 2, MeOH, (S)-TolBINAP, 80ºC 94%, 48% ee (-)

42. 42 Homogeneous Catalysis 6. Asymmetric Reactions C. Gonzalez-Arellano, A. Corma, M. Iglesias, F. Sanchez Chem. Commun. 2005, 3451-3153. 6.3 Asymmetric Hydrogenation

43. 43 Homogeneous Catalysis Recent Literature: Nucleophilic Attack to Unactivated Alkenes 1 C.-G. Yang, C. He J. Am. Chem. Soc. 2005, 127, 6966-6967. 12 3 2 J. Zhang, C.-G. Yang, C. He J. Am. Chem. Soc. 2006, 128, 1798-1799. 3 C. Brouver, C. He Angew. Chem. Int. Ed. 2006, 45, 1744-1747.

44. 44 Conclusion Au (I) or Au (III)? A. W. Someck, M. Rubina, V. Gevorgyan J. Am. Chem. Soc. 2005, 127, 10500-10501. R R R 123 AuCl 3 Au(PEt 3 )Cl Toluene, 5 min to 3 days XX X X= Cl, Br, I

45. 45 [[[(Dimethylammino)methylene]amino]-methylene]dimethylammonium Chloride 1 It is a brown solid and it is a β-dimethylaminomethylenating agent for ketones and amines 2 2 J. T. Gupton, C. Colon, C. R. Harrison, M. J. Lizzi, D. E. Polk J. Org. Chem. 1980, 45, 4522-4524. 1 Encyclopedia of Reagents for Organic Synthesis (Ed L.A. Paquette) Vol3, 1995, 2014. Questions? What is the Gold’s reagent?

46. 46 Questions? What is the difference between pink, yellow and white gold? Pink: alloy of gold and copper White: alloy of gold, silver and palladium, coated with rhodium Yellow: alloy of gold with other metals (Karat: measure of gold purity, 24K is pure gold) (Karat: measure of gold purity, 24K is pure gold)