Asymmetric Organocatalysis.ppt

anocatalysis
Sarah Maifeld
September 19, 2002
Approaches to Asymmetric Catalysis
Organometallic catalysis
Broad scope
Ligand control
Inert conditions
Cost and toxicity
anic catalysis
Highly selective
High rate of reaction
Limited scope
Organocatalysis
Similar modes of action
Lewis acidic/Lewis basic functionality
Enzyme mimetics
Advantages
Preparative
Inexpensive
Amenable binatorial approaches
History and Development
Early example
Bredig, G.; Fiske, P. S. Biochem. Z. 1912, 46, 7.
Prelog, V.; Wilhelm, M. Helv. Chim. Acta 1954, 37, 1634.
Applications
ic resolutions
Phase transfer catalysis
Asymmetric synthesis
Outline
Cinchona Alkaloids
Proline
Amino Acid Derivatives
Peptide-like Catalysts
Heteroazolium Species
Cinchona Alkaloids
Enantiomeric b-hydroxyamine functionality
Nucleophilic catalysts
Wynberg, H. Top. Stereochem. 1986, 16, 87.
Asymmetric b-Lactones
Staring, E. G. J.; Wynberg, H. J. Am. Chem. Soc. 1982, 104, 166.Staring, E. G. J.; Wynberg, H. J. Org. Chem. 1985, 50, 1977.
Requires electron deficient aldehydes and aromatic ketones
68 – 98% yield
89 – 98% ee
Alkyl aryl ketones react in trace amounts
Aldol - Lactonization Mechanism
Dijkstra, G. D. H.; Kellog, R. M.; Wynberg, H.; Svendsen, J. S.; Marko, I.; Sharpless, K. B.
J. Am. Chem. Soc. 1989, 111, 8069.
Cortez, G. S.; Tennyson, R. L.; Romo, D. J. Am. Chem. Soc. 2001, 123, 7945.
Methyl Ketene Dimerization
Calter, M. A. J. Org. Chem. 1996, 61, 8006.
Polypropionate Synthesis
Guo, X.; Liao, W.; Calter, M. A. Org. Lett. 2001, 3, 1499.