1. Organo-metal cooperative catalysis♦
3rd year seminar
Tiffany Piou
Supervisors: Dr. Luc Neuville and Prof. Jieping Zhu

2. Transition metal catalysis
One of the most useful and powerful tool in organic chemistry.
Examples of transition metal reactions:
Cross-coupling
Hydroformylation
Alkene and alkyne metathesis
Hydrogenation
Cyclopropanation
Hydroamination
Hydroesterification
Hydrocarboxylation
Pauson-Khand reaction
Isomerisation of olefins
Hydrocyanation
Advantages:
Chemoselectivity
Regioselectivity
Stereoselectivity
High yield
Reproducibility
Low catalyst loading
Transition Metals for Organic Synthesis: Building Blocks and Fine Chemicals (Eds.: M. Beller, C. Bolm),
Wiley-VCH, Weinheim, 2nd ed., 2004, vol. 1 and 2.

3. Organocatalysis Major topic in organic chemistry
Access to enantiomerically enriched molecules
Explosion of new organocatalysts
Main advantages:
Not expensive
Easily accessible
Stable to air and moisture
Enantioselective Organocatalysis: Reactions and Experimental Procedure (Ed,: P. I. Dalko), Wiley-VCH, Weinheim, 2007.

4. Cooperation between transition metal and organocatalyst
Concept introduced by Krische in 2003.
Combine Morita-Baylis-Hillman type reaction and Tsuji-Trost reaction
Use of “non classical” electrophilic partner
Open new perspectives
B. G. Jellerichs, J.-R. Kong, M. J. Krische J. Am. Chem. Soc. 2003, 125,

5. Cooperative catalysis
Cooperation between transition metal and organocatalyst
New tool in organic chemistry
Cooperative catalysis
Unprecedented transformations not currently possible with the transition metal or the organocatalyst alone.
Problem: compatibility?
C. Zhong, X. Shi, Eur. J. Org. Chem. 2010,
Z. Shao, H. Zhang, Chem. Soc. Rev. 2009, 38,

6. Two different types of cooperation
The two catalysts
operate simultaneously
The two catalysts operate
Successively in a “one pot” fashion
C. Zhong, X. Shi, Eur. J. Org. Chem. 2010,
Z. Shao, H. Zhang, Chem. Soc. Rev. 2009, 38,

7. Two different types of cooperation
The two catalysts
operate simultaneously
The two catalysts operate
Successively in a “one pot” fashion
C. Zhong, X. Shi, Eur. J. Org. Chem. 2010,
Z. Shao, H. Zhang, Chem. Soc. Rev. 2009, 38,

8. Cooperative Reactions:
Brönsted acid/base
Aminocatalysis
Lewis Base
Cooperative Reactions:
Transition Metal +
Organocatalyst
NHC organocatalyst
Bifunctional catalyst
C. Zhong, X. Shi, Eur. J. Org. Chem. 2010,
Z. Shao, H. Zhang, Chem. Soc. Rev. 2009, 38,

9. Transition metal with aminocatalysis
Pioneering work by Barbas, List and MacMillan
Amine activations are the most studied organocatalytic system
Functionnalization of carbonyl compounds
One of the most popular strategies in cooperative catalysis
S. Mukherjee, J. W. Yang, S. Hoffmann, B. List, Chem. Rev. 2007, 107,

10. Intermolecular α-allylation
First example, Cordova et al. in 2006,
Breit et al. in 2009,
No stereoselectivity
I. Ibrahem, A. Cordova, Angew. Chem. Int. Ed. 2006, 45,
I. Usui, S. Schmidt, B. Breit, Org. Lett. 2009, 11,

11. Intramolecular α-allylation
Saicic et al. in 2007,
2009,
Chiral amine catalysts tested failed
F. Bihelovic, R. Matovic, B. Vulvovic, R. N. Saicic, Org. Lett. 2007, 9,
B. Vulvovic, F. Bihelovic, R. Matovic, R. N. Saicic, Tetrahedron 2009, 65,

12. Enamine addition to activated alkyne
Multicomponent reaction developed by Wu’s group in 2007,
Tandem reaction published by Dixon’s,
Q. Ding, J. Wu, Org. Lett. 2007, 9,
T. Yang, A. Ferrali, L. Campbell, D. J. Dixon, Chem. Commun. 2008,

13. Enamine induced enantioselective cooperative reaction
Nishibayashi et al in 2010,
M. Ikeda, Y. Miyake, Y. Nishibayashi, Angew. Chem. Int. Ed. 2010, 49,

14. Enamine catalysis with SOMO photoredox catalysis
SET = single electron transfer
A. Nicewicz, D. W. C. MacMillan, Science 2008, 322,

15. Cooperative Reactions:
Brönsted acid/base
Aminocatalysis
Lewis Base
Cooperative Reactions:
Transition Metal +
Organocatalyst
NHC organocatalyst
Bifunctional catalyst

16. Chiral Brönsted-acid/base with metal activated substrates
Chiral Brönsted acid/base catalyst: a powerful strategy.
In combination with transition-metal, 3 approaches:

17. Chiral Brönsted-acid/base with metal activated substrates
Chiral Brönsted acid/base catalyst: a powerful strategy.
In combination with transition-metal, 3 approaches:

18. Asymmetric Counter-Anion-directed catalysis Strategy (ACDC)
First example proposed by Toste et al,
G. L. Hamiltion, E. J. Kang, M. Mba, F. D. Toste, Science 2007, 317,

19. Enantioselective α-allylation of aldehyde via ACDC strategy
List et al.,
G. Jiang, B. List, Angew. Chem. Int. Ed. 2011, 50,

20. Chiral Brönsted-acid/base with metal activated substrates
Chiral Brönsted acid/base catalyst: a powerful strategy.
In combination with transition-metal, 3 approaches:

21. Chiral Brönsted acid activation
Asymmetric alkynylation of α-imino esters proposed by Chan et al.:
Limited scope!
J.-X. Ji, J. Wu, A. S. C. Chan, Proc. Natl. Acad. Sci. USA 2005, 102,

22. Chiral Brönsted acid activation: sp carbon nucleophile
Rueping et al. 2007,
Arndtsen et al.,
Inexpensive catalyst
Large scope
Excellent ee
M. Rueping, A. P. Antonchick, C. Brinkmann, Angew. Chem. Int. Ed. 2007, 46,
Y. Lu, T. C. Johnstone, B. A. Arnsdtsen, J. Am. Chem. Soc. 2009, 131,

23. Chiral Brönsted acid activation: Rh mediated-carbene nucleophile
W.-H. Hu, X.-F. Xu, J. Zhou, W.-J. Liu, H.X. Huang, J. Hu, L. P. Yang, L.-Z. Gong, J. Am. Chem. Soc. 2008, 130,

24. Enantioselective hydrogenation of imine
Beller’s group in 2011,
An alternative to the Hantzsch dihydropyridine
S. Zhou, S. Fleisher, K. Junge, M. Beller, Angew. Chem. Int. Ed. 2011, 50,

25. Chiral Brönsted-acid/base with metal activated substrates
Chiral Brönsted acid/base catalyst: a powerful strategy.
In combination with transition-metal, 3 approaches:

26. Chiral Brönsted base and transition-metal Lewis acid
Enantioselective aza-Henry reaction,
K. R. Knudsen, K. A. Jorgensen, Org. Biomol. Chem. 2005, 3,

27. Chiral Brönsted base and transition-metal Lewis acid
Enantioselective Conia-ene reaction
T. Yang, A. Ferrali, F. Sladojevich, L. Campbell, D. J. Dixon, J. Am. Chem. Soc. 2009, 131,

28. Cooperative Reactions:
Brönsted acid/base
Aminocatalysis
Lewis Base
Cooperative Reactions:
Transition Metal +
Organocatalyst
NHC organocatalyst
Bifunctional catalyst

29. Organic Lewis base with transition-metal activated electrophiles
Krische in 2003,
Few examples probably because of compatibility problems
B. G. Jellerichs, J.-R. Kong, M. J. Krische J. Am. Chem. Soc. 2003, 125,

30. Organic Lewis base catalysed tandem reaction
Wu et al. reported a 3 components reaction,
S. Ye, J. Wu, Tetrahedron Lett. 2009, 50,

31. Cooperative Reactions:
Brönsted acid/base
Aminocatalysis
Lewis Base
Cooperative Reactions:
Transition Metal +
Organocatalyst
NHC organocatalyst
Bifunctional catalyst

32. Bifunctional catalyst
New generation of catalyst
Enhance the compatibility between the metal and the organocatalyst
New strategy for cooperative catalysis

33. Bifunctional organocatalyst in cooperation with transition metal
Jun and co-workers,
C.-H. Jun, H. Lee, H. Lee, J.-B. Hong, Angew. Chem. Int. Ed. 2000, 39,

34. Bifunctional organocatalyst in cooperation with transition metal
Wang et al,
Maximize the compatibility between the Lewis base and Lewis acid
Z. Xu, P. Daka, I. Budik, H. Wang, F. Q. Bai, H.-X. Zhang, Eur. J. Org. Chem. 2009,

35. Cooperative Reactions:
Brönsted acid/base
Aminocatalysis
Lewis Base
Cooperative Reactions:
Transition Metal +
Organocatalyst
NHC organocatalyst
Bifunctional catalyst

36. NHC-mediated reactions
Bode and Glorius in 2004,
Tool to develop enantioselective tandem reaction
Application in cooperative catalysis, but compatibility?
S. Sohn, E. L. Rosen, J. W. Bode, J. Am. Chem. Soc. 2004, 126,
C. Burstein, F. Glorius, Angew. Chem. Int. Ed. 2004, 43,
V. Nair, R. S. Menon, A. T. Biju, C. R. Sinu, R. R. Paul, A. Josea, V. Sreekumarc, Chem. Soc. Rev. 2011, 40,

37. NHC-catalysed cooperative reaction
Scheidt et al. in 2011,
The Lewis acid coordinate and activate the α-ketoester
New class of electrophiles for NHC-catalysed annulation
D. T. Cohen, B. Cardinal-David, K. A. Scheidt, Angew. Chem. Int. Ed. 2011, 50,

38. Conclusion
Cooperative catalysis between transition metal and organocatalyst attracted much interest:
Successfully promoting a variety of transformations
Different combinations of metal and organocatalyst
Development of new reactions
To be continued …