A Fluorinated ”Designer" Organocatalyst

Significance

Gilmour and colleagues report the study and application of commercially available 2-(fluorodiphenylmethyl)pyrrolidine 2 as a secondary amine organocatalyst. The authors hypothesized that a fluorine atom beta to the pyrrolidine nitrogen would lead to a pronounced preference for a gauche conformation of the iminium intermediate of type 1, possibly resulting in enhanced asymmetric induction. Crystallographic and computational studies were used to support this hypothesis. As proof of principle, catalyst (S)-2 was applied to a Weitz-Scheffer epoxidation. The observed enantioselectivity of catalyst (S)-2 proved to be comparable to the original Jørgensen catalyst 4 (J. Am. Chem. Soc. 2005, 127, 6964) and superior to the non-fluorinated analogue 3.