Bicyclic Pyrrolidines for Medicinal Chemistry via [3 + 2]-Cycloaddition
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 de...
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Veröffentlicht in: | Journal of organic chemistry 2021-10, Vol.86 (19), p.13289-13309 |
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Hauptverfasser: | , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
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Zusammenfassung: | 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). |
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ISSN: | 0022-3263 1520-6904 |
DOI: | 10.1021/acs.joc.1c01327 |