Bicyclic Pyrrolidines for Medicinal Chemistry via [3 + 2]-Cycloaddition
Vladimir I Savych1, Vladimir L Mykhalchuk1, Pavlo V Melnychuk1
1Enamine Ltd.; Chervonotkatska 78, 02094 Kyiv, Ukraine, www.enamine.net.
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).
Related Concept Videos
Cycloaddition Reactions: Overview
Cycloaddition Reactions: MO Requirements for Thermal Activation
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Cycloaddition Reactions: MO Requirements for Photochemical Activation
Pericyclic Reactions: Introduction
Pericyclic reactions can be classified into three categories: electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. Electrocyclic reactions and sigmatropic...


