Synthesis of highly functionalized pyrrolidines via a mild one-pot, three-component 1,3-dipolar cycloaddition process

Abstract

A simple and efficient one-pot, three-component synthesis of highly functionalized pyrrolidines via cascade imine → azomethine ylide → 1,3-dipolar cycloadditions is reported. Admixing a variety of aldehydes, dimethyl 2-aminomalonate, and electron deficient alkenes in THF leads to the clean production of pyrrolidines in good to excellent yields. The mild reaction conditions enabled the generation of previously inaccessible azomethine ylides from enolizable aldehydes. Endo selectivity was exclusive with N-phenyl maleimide and maleic anhydride. Good chemo-, regio-, and stereoselectivities were observed with methyl acrylate, though catalysis by Ag(I) was necessary with this dipolarophile. © 2005 American Chemical Society.