1. Baeyer-Villiger Oxidation: Mechanism and Enantioselective Systems
Literature Meeting
Baeyer-Villiger Oxidation: Mechanism and Enantioselective Systems
Jean-Nicolas Desrosiers
January 31, 2005

2. Outline 1. Introduction 2. BV mechanistic studies
3. Enantioselective reactions
3.1 Seminal work by Strukul and Bolm
3.2 Katsuki's systems
3.2.1 Bidentate ligands
3.2.2 Multidentate salen ligands

3. The Discovery of the Baeyer-Villager Oxidation
potassium persulfate donne persulfuric acid ou caro's acid

4. Well-Known and Widely Applied Reaction
Since then , the BV oxidation have been used for...
[O] = peroxides (R2O), peracids (RCOOOH), persulfuric acid...
ten Brink et al. Chem. Rev. 2004, 104, 9, 4105.

5. Well-Known and Widely Applied Reaction
ten Brink et al. Chem. Rev. 2004, 104, 9, 4105.

6. Exploration of the Mechanism
Renz, M.; Meunier, B. Eur. J. Org. Chem. 1999, 737.

7. 18O-Labeled Experiment
Confirmed the presence of the Criegee intermediate
Doering, W. v.; Dorfman, E. J. Am. Chem. Soc. 1953, 75, 5595.

8. Retention of the Stereochemistry of the Migrating Group
based on m.p.
Turner, R. B. J. Am. Chem. Soc. 1950, 72, 878.
based on opt. rot.
pcl3, cdme2
Mislow, K.; Brenner, J. J. Am. Chem. Soc. 1953, 75, 2318.

9. Competitive Migration
p-MeO-Ar > p-Me-Ar > Ph > p-Cl-Ar > p-Br-Ar > p-NO2-Ar
Doering, W. v. et al. J. Am. Chem. Soc. 1950, 72, 5515.

10. Relative Migration Aptitude

11. The Primary and Secondary Effect

12. The Secondary Effect
Noyori, R.; Kobayashi, H.; Sato, T. Tetrahedron Lett. 1980, 21, 2573.

13. The Secondary Effect

14. The Primary Effect According to the migratory aptitudes
Crudden, C. M. et al. Angew. Chem. Int. Ed. 2000, 39, 16, 2851.

15. The Primary Effect Violation of the accepted migratory aptitudes
Crudden, C. M. et al. Angew. Chem. Int. Ed. 2000, 39, 16, 2851.

16. Is the Dipole/Dipole Interaction the Primary Factor?
Crudden, C. M. et al. Angew. Chem. Int. Ed. 2000, 39, 16, 2851.

17. Is the Dipole/Dipole Interaction the Primary Factor?
Crudden, C. M. et al. Angew. Chem. Int. Ed. 2000, 39, 16, 2851.

18. The Rate-Determining Step of the BV oxidation
Beckman LSlOO liquid scintillation counter,
The rate-determining step changes from addition to migration with a change of substituents.
Palmer, B.W. et al. J. Am. Chem. Soc. 1970, 92, 2580.

19. Electrophilic and Nucleophilic Activation of the BV reaction.

20. Outline 1. Introduction 2. BV mechanistic studies
3. Enantioselective reactions
3.1 Seminal work by Strukul and Bolm
3.2 Katsuki's systems
3.2.1 Bidentate ligands
3.2.2 Multidentate salen ligands

21. Seminal Work on Enantioselective BV

22. Proposed Mechanism for the Enantioselective BV

23. Bolm's Enantioselective System

24. Bolm's Enantioselective System

25. Bolm's Optimized Results
Several sources of metal were screened (Cu, Mg, Zr, Al)
Bolm, C. et al. Synlett 2004, 9, 1619.

26. Katsuki's Biography Tsutomu Katsuki
1988 University of Kyushu, Professor
1980 University of Stanford & MIT, Post-doctoral fellow
Prof. K. B. Sharpless
1976 University of Kyushu, Ph.D.
Prof. M. Yamaguchi
1969 University of Kyushu, B.Sc.

27. Proposed Enantioselective BV System
high conformational
freedom
bulky R'
selective
migration
selective
addition
A metal complex bearing two vacant cis-coordinating sites should
be suitable for asymmetric B-V reaction.
Katsuki, T. et al. Helv. Chim. Acta. 2002, 85, 3078.

28. Screening Palladium(II) Complexes With Bidentate Ligands
Katsuki, T. et al. Synlett 2003, 5, 643.

29. Optimization of Solvent and Temp
Katsuki, T. et al. Synlett 2003, 5, 643.

30. Few Substrates Tried
Katsuki, T. et al. Synlett 2003, 5, 643.

31. Square Planar Complexes
Square planar complex with trans vacant coordinating sites
Katsuki, T. et al. Tet. Lett. 2001, 41, 6911.

32. Obtaining Vicinal Vacant Coordinating Sites
cis-b [Mn(III) L1(acac)]
Che, C.-M. et al. J. Chem. Soc. Dalton Trans. 1997, 3479.

33. Enantioselectivity with cis- Complex
- The control of the chelate conformation is not sufficient
Katsuki, T. et al. Tet. Lett. 2001, 41, 6911.

34. Forced cis- Structure via a Zr Complex
slow opening
active
species
Katsuki, T. et al. Tetrahedron Lett. 2001, 42, 3873.
Fixed conformation
of the moiety

35. Results Obtained With Zr Complexes
Katsuki, T. et al. Tetrahedron Lett. 2002, 43, 4481.

36. Optimization of Reaction Conditions
Katsuki, T. et al. Tetrahedron Lett. 2002, 43, 4481.

37. Formation of Normal and Abnormal Lactones
Katsuki, T.et al. Proc. Natl. Acad. Sci. USA 2004, 101, 5737.

38. Relative Reaction Ratio of Enantiomers

39. Increasing Conversions
Katsuki, T.et al. Proc. Natl. Acad. Sci. USA 2004, 101, 5737.

40. Screening Substrates

41. Conformation Study of the Catalyst
Katsuki, T.et al. Proc. Natl. Acad. Sci. USA 2004, 101, 5737.

42. Conformation Study of the Catalyst

43. Conformation Study of the Catalyst
h202 plus nucleophile, et cycle à 5 favorisé plus que cycle à 6
curtin-hammet

44. Conclusions