| The stereoselective formation of six-membered nitrogen heterocycles with an asymmetric quaternary carbon center could be achieved through aza-annulation of {dollar}beta{dollar}-enamino amide substrates, prepared by a condensation of a racemic {dollar}beta{dollar}-keto amide with an optically active primary amine, and activated acrylate derivatives. A variety of different {dollar}beta{dollar}-enamino amide substrate classes were examined in this reaction. When aza-annulation reaction was performed with an {dollar}alpha{dollar}-acetamido substituted acrylate derivative, the quaternary carbon center was formed stereoselectively, but poor selectivity was observed for generation of the stereogenic center {dollar}alpha{dollar} to lactam carbonyl.; The aza-annulation reaction provides an efficient route for the potential construction of the heterocyclic 2-pyridone framework for complex bioactive compounds, such as natural product targets or synthetic peptide mimetics. Peptide analogs could be assembled in three steps and in good overall yield.; The aza-annulation was then shown to constitute a quick and efficient method of building up isoquinoline derivatives, which might serve as non-benzodiazepine sleep inducing drugs. |
