Stereoselective Multicomponent Assembly of Enantiopure Oxazolopiperidines and -azepines

• DOI: 10.1021/jo202455c
• Publication Date: 2012-01-24T11:49:45Z
• Authors: Nicolas Zill; Angèle Schoenfelder; Nicolas Girard; Maurizio Taddei; André Mann
• Keywords: Enantiopure drug

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 appendant oxygen. On basis series different experimental conditions, diastereocontrol observed during formation is best explained stereoelectronic effect induced A(1,3)-strain in common intermediate (A). This new sequence suitable for diversity oriented syntheses, allowing enantiopure (S)- (R)-coniceine five steps commercially available material.