Bicyclic Pyrrolidines for Medicinal Chemistry via [3 + 2]-Cycloaddition
Vladimir I. Savych, Vladimir L. Mykhalchuk, Pavlo V. Melnychuk, Andrii O. Isakov, Taras Savchuk, Вадим М. Тимошенко, Sergiy A. Siry, Sergiy O. Pavlenko, Dmytro V. Kovalenko, Oleksandr V. Hryshchuk, Vitalii A. Reznik, Bohdan A. Chalyk, Vladimir S. Yarmolchuk, Эдуард Б. Русанов, Pavel K. Mykhailiuk
Abstract
A general approach to bicyclic fused pyrrolidines via [3 + 2]-cycloaddition between nonstabilized azomethyne ylide and endocyclic electron-deficient alkenes was elaborated. “Push–pull” alkenes and CF3-alkenes did not react with the azomethyne ylide under the previously reported conditions, and we developed a superior protocol (LiF, 140 °C, no solvent). Among obtained products were medchem-relevant bicyclic sulfones, monofluoro-, difluoro-, and trifluoromethyl-substituted pyrrolidines. This approach not only allowed preparation of novel molecules but also significantly simplified synthesis of the existing ones (e.g., sofinicline).