Diastereo- and enantioselective three-component coupling approach to highly substituted pyrrolidines
Mani Raj Chaulagain1, Albert E Felten, Kevin Gilbert
1Department of Chemistry, Indiana University , 800 E. Kirkwood Avenue, Bloomington, Indiana 47405-7102, United States.
Abstract:
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.
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