Multicomponent reactions (MCRs) are atom economic processes in which three or more reactants come together and form highly functionalized products. Inexpensive and readily-available starting materials are used in these one-pot reactions. This work describes the study of an imine-based MCR, the Ugi-Smiles reaction. Imines, prepared from allyl amine and substituted 2-furaldehydes, were discovered to react in an 3 component coupling Ugi-Smiles Diels-Alder tandem process along with isocyanide and phenol components to efficiently generate epoxyisoindolines. The effect of preformed imine on product formation was studied.

Herein we report the discovery of a novel, imine-based tandem Ugi-Smiles/IMDAF process. Our goals focus on the development of this process to improve yields of diastereomeric products. Reaction optimization studies and functional group variation of components provide insight for application to the synthesis of a small library of biologically-active products. Additional studies aimed to compare the imine-based 3 component coupling Ugi-Smiles/IMDAF process to the standard 4 component coupling Ugi-Smiles/IMDAF to determine methods providing the best yields.