%0 Journal Article
%A Yokoyama, Akihiro
%A Ohwada, Tomohiko
%A Shudo, Koichi
%D 1998
%T Prototype Pictet−Spengler Reactions Catalyzed by Superacids.
Involvement of Dicationic Superelectrophiles
%U https://acs.figshare.com/articles/journal_contribution/Prototype_Pictet_Spengler_Reactions_Catalyzed_by_Superacids_Involvement_of_Dicationic_Superelectrophiles/3716472
%R 10.1021/jo982019e.s001
%2 https://acs.figshare.com/ndownloader/files/5808036
%K methylene
%K protonated imines
%K diprotonated imines
%K Dicationic Superelectrophiles
%K Pictet
%K latter reaction
%K hydroxy group
%K tetrahydroisoquinoline
%K cyclizing benzene ring
%K parent N
%K prototype cyclization
%K reaction media
%K TFA
%K monoprotonated imine
%K dicationic superelectrophiles
%K protonative activation
%X 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 N-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 N-methylene-2-phenethylamine and related imines, strongly supporting the intervention of an additional
protonative activation of the N-protonated imines, that is, the involvement of dicationic superelectrophiles, N,N-diprotonated imines (ammonium−carbenium dications). We further found that the
prototype cyclization of the parent N-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 N-methylene-2-phenethylamine can thus take place both through the monocation (the N-monoprotonated imine)
and the dication (the N,N-diprotonated imine), the latter reaction being predominant in superacids.
%I ACS Publications