Application of Polyamines and Amino Acid Derivatives Based on 2-Azabicycloalkane Backbone in Enantioselective Aldol Reaction

Carbon-carbon bond forming reactions, such as aldol reaction and condensation, belong to extremely desired transformations as manifested by >25,000 entries in SciFinder. Their stereoselective variant requires the use of an appropriate catalyst with a strictly defined structure. Hence, chiral 2-azabicycloalkane-based catalysts were designed, synthesized and tested in a stereoselective aldol reaction between cyclic/acyclic ketone and p-nitrobenzaldehyde both in organic and aqueous media. Among catalysts containing a chiral bicyclic backbone, amide based on 2-azabicyclo[3.2.1]octane and pyrrolidine units showed the best catalytic activity and afforded aldol product in excellent chemical yields (up to 95%) and good diastereo- and enantioselectivity (dr 22:78, ee up to 63%).

Automated summary

Chiral 2-azabicycloalkane-based catalysts were designed, synthesized and tested, showing excellent catalytic activity and selectivity in aldol reactions. By optimizing the catalyst structure, aldol products were successfully synthesized with high yields up to 95%.