Overcoming Deactivation of Amine-Based Catalysts: Access to Fluoroalkylated γ-Nitroaldehydes.

Organocatalytic conjugate addition reactions of aldehydes to fluoroalkylated nitroolefins with chiral amine catalysts offer a straightforward stereoselective path to fluoroalkylated γ-nitroaldehydes and downstream derivatives. However, amine-based catalysts suffer from deactivation by reaction with electron-poor fluoroalkylated nitroolefin. Here, we show that catalyst deactivation can be overcome by catalysts that bear an intramolecular acid for protonation and release of the alkylated catalyst through ß-elimination of the nitroolefin. NMR spectroscopic, kinetic, and molecular modeling studies provided detailed structural and mechanistic insights into the factors that control reversible catalyst alkylation and facilitate efficient catalysis.