Synthesis of Tetrazole-Derived Organocatalysts via Azido-Ugi Reaction with Cyclic Ketimines

A new route to tetrazole-derived
cyclic amines based on the TMSN3-modified Ugi reaction
with 2-substituted cyclic imines was
elaborated. The reaction allows the direct preparation of five-, six-,
and seven-membered cyclic amines substituted with a tetrazole ring,
which are important types of organocatalysts. The scope and limitations
of this method are discussed. In the case of the Ugi reaction with
benzyl isocyanide, the N-substituted tetrazoles can be easily debenzylated
under catalytic hydrogenation conditions to form NH-tetrazoles in
quantitative yields. It was demonstrated that both enantiomers of
tetrazole-derived cyclic amines can be prepared by resolution with
tartaric acid, thereby initiating a simple route to chiral derivatives.
One of the obtained chiral tetrazoles was efficiently used as an organocatalyst
in the amination reaction.