Stereoselective Multicomponent Assembly of Enantiopure Oxazolopiperidines and -azepines

A multicomponent reaction (MCR) based on a cyclohydrocarbonylation (CHC) driven by hydroformylation was set up toward the efficient diastereoselective preparation of oxazolopiperidines (<b>4a</b>–<b>e</b>) and -azepines (<b>7a</b>–<b>d</b>). The bicyclic oxazolidines were obtained from chiral <i>N</i>-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 (<b>A</b>). This new sequence is suitable for diversity oriented syntheses, allowing the preparation of enantiopure (<i>S</i>)- and (<i>R</i>)-coniceine in five steps from commercially available material