Synthesis Applications of Cationic Aza-Cope Rearrangements. Stereoselective synthesis of cis- and trans-3a-Aryl-4-oxodecahydrocycloheptapyrroles

Article abstract of DOI:10.1021/jo00168a006

A general synthesis of 3a-aryl-4-oxodecahydrocycloheptapyrroles is detailed (eq 1, n=2).The key step is a "ring-enlarging pyrrolidine annulation" reaction which occurs when 2-amino-1-(1-arylvinyl)cyclohexanols are treated at 25-80 deg C with an aldehyde and acid.Three different methods (Schemes I and II) for assembling the 2-amino-1-(1-arylvinyl)cyclohexanol intermediates are reported. cis-3a-Aryl-4-oxodecahydrocycloheptapyrroles can be formed with complete stereocontrol from either cis- or trans-2-amino-1-(1-arylvinyl)cyclohexanols.The corresponding trans bicyclics can be prepared with modest (ca. 3:1) selectivity from cis-2-<(diphenylmethyl)amino>-1-(1-arylvinyl)cyclohexanols.The stereochemical outcome of these tandem cationic aza-Cope-Mannich cyclization reactions is consistent with chair topographies for the rearrangment steps (Scheme III).