Stereoselectivity of superacid-catalyzed Pictet-Spengler cyclization reactions.

[reaction: see text] High stereoselectivities were found in a wide range of superacid-catalyzed Pictet-Spengler cyclization reactions. Particularly in the cases of 2-alkyl-N-benzylidene-2-phenethylamines, an enhanced stereoselectivity was observed under the superacid conditions as compared with the corresponding weak acid (TFA)-catalyzed (monocationic) cyclization reaction of the N-benzylidene-2-(3',4'-dimethoxy)phenethylamines that bear electron-donating groups on the cyclizing aromatic ring. The computational study also supported the energetic favorability of the cyclization of the N,N-diprotonated imine and revealed a significantly early transition-state structure.