Diastereo- and Enantioselective Three-Component Coupling Approach to Highly Substituted Pyrrolidines

The
enantioselective synthesis of substituted pyrrolidines through
a mild Lewis-acid catalyzed three-component coupling reaction between
picolinaldehyde, amino acids, and activated olefins is reported. The
reaction uses low catalyst loadings of commercially available chiral
diamines and copper triflate proposed to self-assemble in conjunction
with the chelating aldehydes, 4-substituted-2-picolinaldehydes or
4-methylthiazole-2-carboxaldehyde, to generate a catalyst complex.
A model is provided to explain how this complex directs enantioselectivity.
This work represents a significant advance in the ease, scope, and
cost of producing highly substituted, enantioenriched pyrrolidines.