Publication Date

April 2015

Advisor(s)

Michael Calter

Major

Chemistry

Language

English (United States)

Abstract

The Feist-Bénary reaction involves the addition of a β-dicarbonyl compound to an α-halo ketone, followed by dehydration to form a highly substituted furan species. When “interrupted” prior to the dehydration step, the reaction furnishes functionalized hydroxyhydrofuran moieties with one to two chiral centres. An asymmetric, “interrupted” Feist-Bénary reaction (abbreviated as IFB reaction) could therefore prove to be a valuable synthetic tool in the synthesis of natural/bioactive molecules. This project aims at optimizing the IFB reaction between cyclic 1,3-diones and α-halo vicinal diketones- a reaction that could lead to efficient syntheses of molecules like the anti-fungal agent gmelinol. The IFB reaction between dimedone and 3-bromo-1-phenyl-propane-1,2-dione has been studied. Initial work involved investigation into the effects of solvent, temperature, base and catalyst on the non-enantioselective reaction. It has been shown that tertiary amine catalysis is necessary for the reaction to occur and that best yields of the racemic IFB reaction are obtained in non-polar solvents, at temperatures of 0oC or more, using proton sponge as base in lieu of potassium carbonate. The second phase of the project involved screening cinchona alkaloid derived catalysts to find a catalyst that furnishes the hydroxyhydrofuran product with maximum enantioselectivity and yield. The catalysts tested were primarily pyrimidine bisquinidyl ethers. 2-((o-phenyl)phenyl)-5-phenylpyrimidine-bis-(9-O-quinidyl) ether has thus far proven to be the best performing catalyst, returning an enantiomeric excess of 73%. Thus, a protocol that gives moderate enantioselectivities and moderate yields has been developed for the IFB reaction between dimedone and 3-bromo-1-phenyl-propane-1,2-dione.

Share

COinS
 

© Copyright is owned by author of this document