Homogeneous Gold Catalysis – A Reactivity Perspective

1. Homogeneous Gold Catalysis – A Reactivity Perspective Dongxu Shu Tang Research Group 12, 10, 2009

2. Contents • Relativistic effect and reactivity • π-acidity reactivity • Gold catalyzed coupling reaction • Summary

3. Features of Gold Catalysis • π-acidity: soft Lewis acid, preferentially activate π-systems • AuI and AuIII • AuI: d10, linear bicoordinate geometry, difficult in asymmetric catalysis • Noβ-H elimination • Reluctant to undergo oxidative addition and reductive elimination

4. Relativistic Effect • Lower 6s and 6p, higher 5d Pyykko, P. et al. Acc. Chem. Res. 1979, 12, 276. 4

5. Origin of π–acidity and Alkynophilicity • π-acidity of R3PAu+ • lower LUMO 2) poor back donation • Alkynophilicity 1) kinetic in origin 2) LUMO of alkyne is lower ΔG ≈ -10 kcal/mol Hertwig, R. H. et al. J. Phys. Chem.1996, 100, 12253. Toste, F. D. et al. Nature.2007, 446, 395.

6. Contents • Relativistic effect and reactivity • π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene • Gold catalyzed coupling reaction • Summary

7. π-AcidityReactivity

8. Carbene or Carbocation Fürstner, A. et al. Angew. Chem. Int. Ed. 2009, 48, 2510. 8

9. Carbene or Carbocation Goddard, W. A. Toste, F. D. et al. Nature Chem. 2009, 1, 482. 9

10. Early Research Thomas, C. B. et al. J. Chem. Soc. Perkin Trans. II1976, 1983. Teles, J. H. et al. Angew. Chem. Int. Ed. 1998, 37, 1415.

11. Stereoselectivity and Regioselectivity Hashmi, A. S. K. et al. Angew. Chem. Int. Ed. 2009, 48, 8247.

12. Contents Relativistic effect and reactivity π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene Gold catalyzed coupling reaction Summary 12

13. Reactivity Pattern of Enyne Furstner, A. et al. Angew. Chem. Int. Ed. 2008, 47, 5030.

14. Cycloisomerization of 1,6-Enyne With Skeletal Rearrangement SingleCleavage Echavarren, A.M. et al. Angew. Chem. Int. Ed. 2004, 14, 2402. DoubleCleavage Echavarren, A.M. et al. Angew. Chem. Int. Ed. 2005, 44, 6146.

15. Mechanism – From Cyclobutene? Echavarren, A.M. et al. Chem. Eur. J. 2006, 12, 5916.

16. Mechanism of Skeletal Rearrangement SingleCleavage DoubleCleavage Echavarren, A.M. et al. Chem. Eur. J. 2006, 12, 5916.

17. Mechanism of Skeletal Rearrangement Toste, F. D. et al. J. Am. Chem. Soc. 2007, 129, 5838.

18. Contents Relativistic effect and reactivity π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene Gold catalyzed coupling reaction Summary 18

19. Propargylic Ester Reactivity Pattern Nolan, S. P. et al. Angew. Chem. Int. Ed. 2007, 46, 2750.

20. 5-exo-dig VS 6-endo-dig Nolan, S. P. et al. Angew. Chem. Int. Ed. 2006, 45, 3647. 20 Toste, F. D. et al. J. Am. Chem. Soc. 2009, 131, 4513.

21. Carbene Reactivity through 5-exo-dig Uemura, S. et al. Tetrahedron Lett. 2003, 44, 2019. Toste, F. D. et al. J. Am. Chem. Soc. 2005, 127, 18002. 21

22. Allene Activation through 6-endo-dig Zhang, L. et al. J. Am. Chem. Soc. 2005, 127, 16804. Zhang, L. et al. J. Am. Chem. Soc. 2007, 129, 11358.

23. Contents Relativistic effect and reactivity π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene Gold catalyzed coupling reaction Summary 23

24. Vinyl Allene as Substrate Malacria, M. et al. J. Am. Chem. Soc. 2009, 131, 2993.

25. Vinyl Allene as Substrate Malacria, M. et al. J. Am. Chem. Soc. 2009, 131, 2993.

26. Allene for Cycloaddition Toste, F. D. et al. J. Am. Chem. Soc. 2009, 131, 6348. Mascarenas, J. L. et al. J. Am. Chem. Soc. 2009, 131, 13020.

27. Contents Relativistic effect and reactivity π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene Gold catalyzed coupling reaction Summary 27

28. Early Investigation Kochi, J. K. et al. J. Organomet. Chem. 1974, 64, 411. Kochi, J. K. et al. J. Am. Chem. Soc. 1976, 98, 7599.

29. Gold Catalyzed Coupling Reaction Corma, A. et al. Angew. Chem. Int. Ed. 2007, 46, 1536. Guo, R. et al. J. Am. Chem. Soc. 2009, 131, 386.

30. Combine the π-acidity and Coupling Reactivity

31. Combine the π-acidity and Coupling Reactivity Hashmi. A. S. K. et al. Eur. J. Org. Chem. 2006, 1387.

32. Combine the π-acidity and Coupling Reactivity Wegner. H. A. et al. Chem. Eur. J. 2008, 14, 11310.

33. Oxidative Coupling Zhang. L. et al. Angew. Chem. Int. Chem. 2009, 48, 3112.

34. Oxidative Coupling Zhang. L. et al. Angew. Chem. Int. Chem. 2009, 48, 3112.

35. Zhang. L. et al. Angew. Chem. Int. Chem. 2009, 48, 3112.

36. Gold and Palladium Combined for Cross-Coupling Hashmi, A. S. K. et al. Angew. Chem. Int. Ed. 2009, 48, 8283. Blum, S. D. et al. Organometallics. 2009, 28, 1275.

37. Summary π-acidity reactivity Complexity 1. substrate design 2. coupled with known reactivity (Nazarov, cycloaddition, carbocation) 3. tandem Gold catalyzed coupling reaction Combine π-acidity reactivity and coupling reaction 1. Generate more complexity 2. from stoichiometric to catalytic 37

38. Acknowledgement Professor Weiping Tang Tang Group Practice talk attendees Katherine Myhre Jenny Werness Wei Zhang Renhe Liu Dr. Suqing Zheng Xiaoxun Li Dr. Min Zhang Patrick Robichaux Na Liu Kyle Dekorver Tianning Diao 38

39. Goddard, W. A.; Toste, F. D. et al. Org. Lett. 2009, 11, 4798. 39 Mascarenas, J. L. et al. J. Am. Chem. Soc. 2009, 131, 13020.

40. Relativistic Effect • m=m0/[1-(v/c)2]1/2 • r decrease as m increase • v increase, m increase, radius decrease, s and p orbital lower, d higher • Unusual higher electronegativity, ionization energy, lower 6s and 6p (LUMO), higher 5d, strong Au-L bond Pyykko, P. et al. Acc. Chem. Res. 1979, 12, 276.

41. General Reactivities of Gold Catalysis • π-Acidity: • Traditional organometallic reactivity: Oxidative addition and reductive elimination Transmetallation • C-H activation: • Hydrogenation and Oxidation