Date of Award
Bachelor of Science
James Adrian, Jr.
ketones, catalytics, reaction, enantioselectivity, chemistry
The aza-Michael addition to unsaturated ketones under neutral to mildly basic condition is a difficult transformation due to the inherent unreactivity of ketones toward the addition of weak nucleophiles. This thesis reports on efforts to develop an environmentally friendly, stereoselective and low-cost organo-catalyzed aza-Michael reaction between unsaturated ketones and nitrogen nucleophiles, such as phthalimide, under neutral to mildly basic conditions using the most inexpensive chiral secondary amine catalyst, proline.1 Both proline and the organic base triethylamine were found to be catalytic in the testing platform of cyclohexen-2-one and phthalimide, and another testing platform of 4-hexen-3-one and phthalimide. Likewise, when screened against proline derivatives and imidazolines (all secondary amines), proline demonstrated the highest yield and enantioselectivity for aza-Michael Addition reactions to ketones. Triethylamine was also determined to be the optimal organic base co-catalyst, in terms of enantioselectivity. The yield and enantioselectivity both heavily depend upon the organic solvent used; indeed, the organic solvent acetonitrile was ideal for yield of the reactions, though with a low enantioselectivity; however, ethyl acetate demonstrated the highest enantioselectivity, but with a lower yield. The highest enantioselectivity observed was 80% ee.
Potter, Bowman, "Progress towards an Aza-Michael Addition to Ketones" (2011). Honors Theses. 1046.