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 Au I and Au III Au I : d 10, 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.

5 Origin of π –acidity and Alkynophilicity π -acidity of R 3 PAu + 1)lower LUMO 2) poor back donation Alkynophilicity 1) kinetic in origin 2) LUMO of alkyne is lower Hertwig, R. H. et al. J. Phys. Chem. 1996, 100, Toste, F. D. et al. Nature. 2007, 446, 395. ΔG -10 kcal/mol

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 π -Acidity Reactivity

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

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

10 Early Research Thomas, C. B. et al. J. Chem. Soc. Perkin Trans. II 1976, Teles, J. H. et al. Angew. Chem. Int. Ed. 1998, 37, 1415.

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

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

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 Echavarren, A.M. et al. Angew. Chem. Int. Ed. 2004, 14, Echavarren, A.M. et al. Angew. Chem. Int. Ed. 2005, 44, Single Cleavage Double Cleavage

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

16 Mechanism of Skeletal Rearrangement Single Cleavage Double Cleavage Echavarren, A.M. et al. Chem. Eur. J. 2006, 12, 5916.

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

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

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, 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, Toste, F. D. et al. J. Am. Chem. Soc. 2005, 127,

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

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

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

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

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, Guo, R. et al. J. Am. Chem. Soc. 2009, 131, 386.

Combine the π-acidity and Coupling Reactivity

Hashmi. A. S. K. et al. Eur. J. Org. Chem. 2006, 1387.

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

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

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, 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

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

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

Relativistic Effect m=m 0 /[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.

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