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

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

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

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.

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

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

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

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.

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.

Relative Migration Aptitude

The Primary and Secondary Effect

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

The Secondary Effect

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

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

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

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

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.

Electrophilic and Nucleophilic Activation of the BV reaction.

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

Seminal Work on Enantioselective BV

Proposed Mechanism for the Enantioselective BV

Bolm's Enantioselective System

Bolm's Enantioselective System

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

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.

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.

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

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

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

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

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

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

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

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

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

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

Relative Reaction Ratio of Enantiomers

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

Screening Substrates

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

Conformation Study of the Catalyst

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

Conclusions