1. Catalysis of Michael Reactions
with Modified Cinchona Alkaloids
Catalyst 2
Catalyst 1
Quinine and Cinchonine are chiral alkaloids found in the bark of Cinchona trees.1 Although quinine is best known as an anti-malarial drug, chemists have started to explore the ability of quinine and other cinchona alkaloids to catalyze asymmetric reactions.2,3 In my research project, I attempted to create an asymmetric catalyst for Michael reactions, an important set of organic reactions, by adding different tethers onto both quinine and cinchonine’s hydroxyl groups (A and B). B A
Quinine
Cinchonine
GC Results for Michael Reaction
Future Considerations
Michael Reactions
Diastereomeric Ketalation
(for analysis of Michael products)
Analyze Michael products using chiral GC
Try different conditions for Michael reaction
Try catalysts with additional Michael reactions
De-protect phenol on Catalyst 1
Add to double bond of Catalyst 2 to lengthen tether
Catalyst: Red-Al + Quinine
Catalyst: Red-Al + 1
Catalyst: Red-Al + 2
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The GC results indicate that quinine and both Catalysts 1 and 2 are not asymmetric catalysts for the Michael reaction between dimethyl malonate and 2-cyclopentene-1-one under the conditions used in this study. Kelsey Hanson’s research, however, shows that quinine can catalyze Michael reactions with enantiomeric excesses of up to 27%.4 These contradictory results suggest that quinine, and possibly Catalysts 1 and 2, may catalyze Michael reactions under different conditions.
49%
Acknowledgements
Dr. William Dasher
Dr. McCormick
Kelsey Hanson
Rachel Safran
References
1. Hobhouse, H. Seeds of Change: Six Plants That Transformed Mankind; Harper & Row: New York, 1986; pp 3-43.
2. Dolling, U. H., Davis, P., Grabowski, E. J. J. Am. Chem. Soc. 1984, 106,
3. Corey, E. J., Noe, M. C., Xu, F. Tetrahedron Lett. 1998, 39, 5347.
4. Hanson, Kelsey; University of Puget Sound, 2003.
By Sarah Strandjord