title: Synthesis of Azabicycles via Cascade Aza-Prins Reactions: Accessing the Indolizidine and Quinolizidine Cores.
abstract: The first detailed studies of intramolecular aza-Prins and aza-silyl-Prins reactions, starting from acyclic materials, are reported. The methods allow rapid and flexible access toward an array of [6,5] and [6,6] aza-bicycles, which form the core skeletons of various alkaloids. On the basis of our findings on the aza-Prins and aza-silyl-Prins cyclizations, herein we present simple protocols for the intramolecular preparation of the azabicyclic cores of the indolizidines and quinolizidines using a one-pot cascade process of N-acyliminium ion formation followed by aza-Prins cyclization and either elimination or carbocation trapping. It is possible to introduce a range of different substituents into the heterocycles through a judicial choice of Lewis acid and solvent(s), with halo-, phenyl-, and amido-substituted azabicyclic products all being accessed through these highly diastereoselective processes.
authors.affiliation: School of Biological & Chemical Sciences, Queen Mary University of London , Mile End Road, London E1 4NS, United Kingdom.
authors.forename: Freda K I
authors.initials: FK
authors.lastname: Chio
authors.affiliation: Department of Chemistry, University of Exeter , Devon EX4 4QD, United Kingdom.
authors.forename: Sébastien J J
authors.initials: SJ
authors.lastname: Guesné
authors.affiliation: AstraZeneca , Alderley Park, Cheshire, SK10 4TG, United Kingdom.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Hassall
authors.affiliation: AstraZeneca , Alderley Park, Cheshire, SK10 4TG, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: McGuire
authors.affiliation: School of Biological & Chemical Sciences, Queen Mary University of London , Mile End Road, London E1 4NS, United Kingdom.|Department of Chemistry, University of Exeter , Devon EX4 4QD, United Kingdom.|School of Science, University of Greenwich , Chatham Maritime, Kent ME4 4TB, United Kingdom.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Dobbs
mesh_terms: D003500:Cyclization; D054836:Indolizidines / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D054837:Quinolizidines / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D054836:Indolizidines; D054837:Quinolizidines