Synthesis and Design of Enantioselective Catalysts

The Feist–Benary reaction, originally used for synthesizing highly substituted furan rings from alpha halocarbonyls and beta ketoesters, has recently been applied by our group to the synthesis of zaragozic acid. The zaragozic acid core provides an interesting intermediate that can be used as a building block for the total synthesis of naturally occurring molecules such as glycinol, rocaglamide, and other complex molecules for their application to the medical field. As in many structures, the stereochemistry of the product is of great importance in determining its physical and chemical properties, so controlling the formation of stereocenters in the Feist-Benary reaction is of great importance. Quinidine, a cinchona alkaloid, has been used as an asymmetric catalyst to control the enantioselectivity of this reaction. Several quinidine derivatives have been pursued by our group and a 92%ee catalyst was achieved that combines a modified pyrimidine scaffold with two quinidine molecules. After refining the conditions for the synthesis of the 92%ee catalyst, a new procedure – the Liebeskind-Srogl coupling reaction – has been applied to the creation of a library of aryl substituted catalysts. The role of electronic interactions in the catalytic mechanism of the Feist–Benary reaction will be better understood through the analysis of the enantioselectivity provided by this library of catalysts.