title: Mechanistic insight into the acid-catalyzed isomerization of biomass-derived polysubstituted pyrrolidines: an experimental and DFT study.
abstract: 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.
authors.affiliation: Instituto de Química Rosario (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina. sarotti@iquir-conicet.gov.ar.
authors.forename: Gabriela G
authors.initials: GG
authors.lastname: Gerosa
authors.affiliation: Instituto de Química Rosario (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina. sarotti@iquir-conicet.gov.ar.
authors.forename: Nicolás
authors.identifier: http://orcid.org/0000-0003-3285-8485
authors.initials: N
authors.lastname: Grimblat
authors.affiliation: Instituto de Química Rosario (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina. sarotti@iquir-conicet.gov.ar.
authors.forename: Rolando A
authors.identifier: http://orcid.org/0000-0003-3701-5807
authors.initials: RA
authors.lastname: Spanevello
authors.affiliation: Instituto de Química Rosario (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina. sarotti@iquir-conicet.gov.ar.
authors.forename: Alejandra G
authors.initials: AG
authors.lastname: Suárez
authors.affiliation: Instituto de Química Rosario (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina. sarotti@iquir-conicet.gov.ar.
authors.forename: Ariel M
authors.initials: AM
authors.lastname: Sarotti