Organocatalytic Asymmetric Inverse-Electron-Demand Aza-Diels-Alder Reaction

Significance

Reported is the first asymmetric ­inverse-electron-demand aza-Diels-Alder reaction of N-sulfonyl-1-aza-1,3-butadienes with aldehydes to afford optically pure piperidines. Optimization of the reaction conditions showed that the chiral secondary amine 1 combined with AcOH gave the best results in terms of enantioselectivity and catalytic activity. Also, the use of water appears to assist the release of the catalyst 1. To ­secure the absolute stereochemistry, an X-ray crystal structure was determined for one of the piperidine derivatives (R^¹ = Et, R^² = Ph, R^³ = 4-MeC₆H₄).