Broadening the Synthetic Scope of the Iron(III)-Catalyzed Aza-Prins Cyclization

Abstract

The nature and influence of the N-sulfonyl group in aza-Prins cyclization and the reactivity of the six-membered aza-cycle generated has been studied. The aza-Prins cyclization of γ,δ-unsaturated amines with a tosyl group at the nitrogen atom produces 2-alkyl-4-halo-1-tosyl-1,2,5,6-tetrahydropyridines with a halovinyl function, extraordinarily stable to further derivatization and detosylation conditions. To modulate the reactivity of such aza-cycles, a general study of the aza-Prins cyclization reaction was performed with several sulfonamides. Ring formation occurs satisfactorily with both N-nosyl and N-mesylamines providing optimal conditions for further synthetic transformations. To exemplify the scope of this methodology, a short synthesis of the alkaloid coniine was successfully carried out.