title: Chiral sulfinamidourea and strong Brønsted acid-cocatalyzed enantioselective Povarov reaction to access tetrahydroquinolines.
abstract: This protocol describes a method for the laboratory synthesis of enantiomerically enriched, chiral tetrahydroisoquinolines through the application of a chiral sulfinamido urea catalyst for the Povarov reaction. Tetrahydroisoquinolines are bicyclic organic frameworks present in a wide assortment of natural and synthetic biologically important compounds including martinelline, scoulerine and tubocurarine. The methodology involves the [4+2] cycloaddition of a N-arylimines with electron-rich olefins such as vinyl lactams and dihydropyrroles in the presence of a two-catalyst system consisting of an achiral strong Brønsted acid (o-nitrobenzenesulfonic acid), together with the chiral sulfinamido urea derivative 1. The anion-binding properties of the urea lead to the association of the ion pair that results from protonation of the imine substrate. Cycloaddition is followed by spontaneous proton loss with re-aromatization to provide the tetrahydroisoquinoline products in highly enantio-enriched form.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Jacobsen
mesh_terms: D000475:Alkenes / Q000737:chemistry; D001557:Benzenesulfonates / Q000737:chemistry*; D061565:Cycloaddition Reaction; D008968:Molecular Conformation; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis*
chemical_list: D000475:Alkenes; D001557:Benzenesulfonates; D044005:Tetrahydroisoquinolines; C448313:3-nitrobenzenesulfonic acid