Regioselective synthesis of spiropyrrolidine/spiropyrrolizidine/spirothiazolidine-grafted macrocycles through 1,3-dipolar cycloaddition methodology

Synthesis of 13- and 16-membered macrocyclic enone with alkyl ether and triazole as a linker was achieved using intramolecular aldol condensation. The newly synthesized macrocyclic enone was successfully utilized as a dipolarophile in 1,3-dipolar cycloaddition (1,3-DC). The dipole generated from isatin/acenaphthenequinone with various secondary amino acids (sarcosine, l-proline, and thiazolidine-4-carboxylic acid) were reacted with macrocyclic enone to give a new class of spiropyrrolidine-grafted macrocycles in good yield (>85%). The structures were assigned by 2D NMR spectra and the regio- and stereochemical outcome of the cycloadducts were established by a single crystal X-ray analysis.