Aza-annulation of enaminones with itaconic anhydride: kinetic preference for exocyclic enamide products

Abstract

Enaminones react with itaconic anhydride in methylene chloride at room temperature to give exocyclic enamides as the major products. These can be readily equilibrated to the thermodynamically more stable endocyclic enamides. In substrates where the exocyclic isomer could not be formed only intractable materials were produced from this reaction. An intermediate in this two step process was detected and identified by proton and 13C NMR spectroscopy. In two cases chiral enaminones were employed and the relative stereochemistry at the new chiral centre in the product was established by a crystal structure of compound 27.