Prototype Pictet−Spengler Reactions Catalyzed by Superacids.
Involvement of Dicationic Superelectrophiles
Akihiro Yokoyama
Tomohiko Ohwada
Koichi Shudo
10.1021/jo982019e.s001
https://acs.figshare.com/articles/journal_contribution/Prototype_Pictet_Spengler_Reactions_Catalyzed_by_Superacids_Involvement_of_Dicationic_Superelectrophiles/3716472
The Pictet−Spengler reaction, an acid-catalyzed intramolecular cyclization of intermediate imines
of 2-arylethylamine to give 1,2,3,4-tetrahydroisoquinolines, has long been limited to active substrates
which bear strongly electron-donating groups such as a methoxy or a hydroxy group on the cyclizing
benzene ring. In this paper, we present superacid-catalyzed Pictet−Spengler reactions of imines of
2-phenethylamine, including the prototype Pictet−Spengler reaction of <i>N</i>-methylene-2-phenethylamine, to give the parent and 1-substituted 1,2,3,4-tetrahydroisoquinolines in moderate to high
yields. The yields are dependent on the acidity of the media. A linear relationship was found between
the rate of the cyclization and the acidity of the reaction media in kinetic studies of <i>N</i>-methylene-2-phenethylamine and related imines, strongly supporting the intervention of an additional
protonative activation of the <i>N</i>-protonated imines, that is, the involvement of dicationic superelectrophiles, <i>N</i>,<i>N</i>-diprotonated imines (ammonium−carbenium dications). We further found that the
prototype cyclization of the parent <i>N</i>-methylene-2-phenethylamine is also catalyzed by TFA to give
1,2,3,4-tetrahydroisoquinoline in good yield, although the cyclization is significantly slower than
that catalyzed by superacids. The prototype Pictet−Spengler cyclization of <i>N</i>-methylene-2-phenethylamine can thus take place both through the monocation (the <i>N</i>-monoprotonated imine)
and the dication (the <i>N</i>,<i>N</i>-diprotonated imine), the latter reaction being predominant in superacids.
1998-12-29 00:00:00
methylene
protonated imines
diprotonated imines
Dicationic Superelectrophiles
Pictet
latter reaction
hydroxy group
tetrahydroisoquinoline
cyclizing benzene ring
parent N
prototype cyclization
reaction media
TFA
monoprotonated imine
dicationic superelectrophiles
protonative activation