Fluorinated Organocatalysts for the Enantioselective Epoxidation of Enals: Molecular Preorganisation by the Fluorine-Iminium Ion Gauche Effect

The fluorine‐iminium ion gauche effect is triggered upon union of a secondary β‐fluoroamine and an α,β‐unsaturated aldehyde, providing a useful strategy for controlling the molecular topology of intermediates that are central to organocatalytic processes. The β‐fluoroamine (S)‐2‐(fluorodiphenylmethyl)pyrrolidine (1) is an effective catalyst for the enantioselective epoxidation of α,β‐unsaturated aldehydes. A process of structural editing has revealed that the efficiency of this catalyst is due to the (fluorodiphenyl)methyl group when it is embedded in a β‐fluoroiminium motif. Epoxidations of challenging cyclic α,β‐disubstituted, β,β‐disubstituted and α,β,β‐trisubstituted enals catalysed by 1 proceed with excellent levels of enantiocontrol (up to 98 % ee). Fluorine finesse! The β‐fluoroamine (S)‐2‐(fluorodiphenylmethyl)pyrrolidine (1) is an effective catalyst for the enantioselective epoxidation of α,β‐unsaturated aldehydes (see scheme). Application of this catalyst to challenging cyclic α,β‐disubstituted enals, β,β‐disubstituted enals, and an α,β,β‐trisubstituted enal proceeds in a highly enantioselective fashion (up to 98 % ee).