Investigation of cis- and trans-4-Fluoroprolines as Enantioselective Catalysts in a Variety of Organic Transformations

Stereoselective fluorination is known to rigidify the ring structure of l-proline, as a result of a combination of electrostatic and hyperconjugative effects associated with the C-F bond. This is a potential strategy for enhancing the enantioselectivity of proline-catalysed reactions. In this study, cis- and trans-4-fluoroprolines were investigated as catalysts in five different organic transformations, including examples of both enamine and iminium ion catalysis. Some significant differences in enantioselectivity were observed between the cis- and trans-isomers of the fluorinated catalysts, confirming that the ring pucker is important. However, no substantial improvements were observed relative to the parent catalyst, l-proline.