Synthesis of Piperidines through Intramolecular Aza-Michael Addition

Significance

Chen, Fan and colleagues developed an intramolecular aza-Michael addition of carbamate-protected amines to enones. The reaction is catalyzed by the combination of the quinine-derived primary/tertiary diamine and trifluoroacetic acid (TFA). The authors present a transition-state model, which includes imine activation of the enone, hydrogen bonding of the protonated tertiary amine to the electron-rich carbamate oxygen, and the minimization of steric interactions. Finally, the presented method is of value for the synthesis of key intermediates towards natural products.