Mechanistic insight into the acid-catalyzed isomerization of biomass-derived polysubstituted pyrrolidines: an experimental and DFT studyElectronic supplementary information (ESI) available: Supplementary figures and tables, compound characterization data, copies of 1H and 13C NMR spectra, full reaction coordinate diagrams and Cartesian coordinates of all compounds. See DOI: 10.1039/c6ob02457b

• Main Authors: Gerosa, Gabriela G, Grimblat, Nicolás, Spanevello, Rolando A, Suárez, Alejandra G, Sarotti, Ariel M
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c6ob02457b

The 1,3-dipolar cycloaddition reactions of azomethine ylides is one of the preferred methods for the synthesis of polysubstituted pyrrolidines. The use of chiral dipolarophiles derived from carbohydrates yields enantiomerically pure pyrrolidines, usually in good to excellent endo selectivities, along with other minor stereoisomers. Recently, we found an unusual isomerization event that allowed the isolation of useful pyrrolidines with relative stereochemistries difficult to obtain otherwise. Although a simple and efficient protocol to promote these transformations was developed, the mechanism was not fully unravelled. Herein, after a combination of experimental, spectroscopic and computational studies (using DFT methods) we propose that this isomerization event takes place through a retro-Mannich//Mannich cascade, via the formation of an iminium ion with E geometry. The mechanism of the acid-catalyzed isomerization of polysubstituted pyrrolidines was unravelled by a combination of experimental, spectroscopic and computational studies.