Regio- and stereoselective synthesis of spiro-pyrrolidine/pyrrolizidine/thiazolidine-grafted macrocycles through intramolecular 1,3-dipolar cycloaddition reaction

Regioselective synthesis of spiropyrrolidine-grafted 11-membered macrocycle was accomplished through an intramolecular [3+2] cycloaddition of azomethine ylides. The key precursor alkenyl diketone (4a-b) was obtained from simple starting materials. The dipole generated from isatin tethered to O-alkyl enone (4a-b) was reacted intramolecularly to yield the spiropyrrolidine-grafted macrocycles (6a-b). The structures of the cycloadducts were assigned by 2D NMR and confirmed by single crystal analysis.