Solid-Phase Synthesis:  Intramolecular Azomethine Ylide Cycloaddition (→Proline) and Carbanilide Cyclization (→Hydantoin) Reactions

An efficient, diastereoselective route to 2,5,6,7-tetrasubstituted-1H-pyrrolo[1,2-c]imidazoles has been developed using solid-phase intramolecular azomethine ylide cycloaddition and carbanilide cyclization chemistries. To successfully execute this eight-step protocol in the solid phase, it was necessary to insert a spacer moiety between the resin and glycinate functional group. Experiments addressing the stereoselectivity of the 1,3-dipolar cycloaddition step as well as the cyclative release step are also presented.