title: Stereoselective multicomponent assembly of enantiopure oxazolopiperidines and -azepines.
abstract: A multicomponent reaction (MCR) based on a cyclohydrocarbonylation (CHC) driven by hydroformylation was set up toward the efficient diastereoselective preparation of oxazolopiperidines (4a-e) and -azepines (7a-d). The bicyclic oxazolidines were obtained from chiral N-alkenylamino alcohols via transient cyclic iminium intermediates that underwent an intramolecular cyclization from the appendant oxygen. On the basis of a series of different experimental conditions, the diastereocontrol observed during the formation of the oxazolidines is best explained by the stereoelectronic effect induced by an A(1,3)-strain in a common cyclic iminium intermediate (A). This new sequence is suitable for diversity oriented syntheses, allowing the preparation of enantiopure (S)- and (R)-coniceine in five steps from commercially available material.
authors.affiliation: Faculté de Pharmacie, UMR 7200, CNRS-Université de Strasbourg, Laboratoire d'Innovation Thérapeutique 74, route du Rhin, F-67401, Illkirch, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Zill
authors.forename: Angèle
authors.initials: A
authors.lastname: Schoenfelder
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girard
authors.forename: Maurizio
authors.initials: M
authors.lastname: Taddei
authors.forename: André
authors.initials: A
authors.lastname: Mann
mesh_terms: D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D001381:Azepines; D010880:Piperidines