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

A novel one-pot synthesis of polysubstituted oxa(thia)zolidin-2-imines has been developed. It employs A(3)-coupling of aldehyde and amine with alkyne to form propargyl amine, which on (thio) amidation with iso(thio)cyanate produces N-propargyl(thio)urea, and a cyclization reaction. A 5-exo-dig iodocyclization of N-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.