One-Pot, Three-Step Copper-Catalyzed Five-/Four-Component Reaction Constructs Polysubstituted Oxa(Thia)zolidin-2-imines

Abstract

A novel one-pot synthesis of polysubstituted oxa(thia)zolidin-2-imines has been developed. It employs A³-coupling of aldehyde and amine with alkyne to form propargyl amine, which on (thio)amidation with iso(thio)cyanate produces <i>N</i>-propargyl(thio)urea, and a cyclization reaction. A 5-<i>exo</i>-dig iodocyclization of <i>N</i>-propargylurea constructs 5-iodomethyleneoxazolidin-2-imine, while cycloisomerization of the thio analogue provides 5-methylenethiazolidin-2-imine. In this process, CuI catalysis has been found to be crucial, and the cyclization occurs through oxygen/sulfur (not nitrogen) nucleophilic attack to alkyne.