P4O10/TfOH mediated domino condensation-cyclization of amines with diacids: a route to indolizidine alkaloids under catalyst- and solvent-free conditions

Abstract

A domino condensation-cyclization method is developed to synthesize indolizidine alkaloids using a P4O10/TfOH reagent system without the employment of either a catalyst or solvent. The use of a few aliphatic and aromatic dicarboxylic acids is shown along with various primary amines. This method is suitable for synthesizing pyrrolo[2,1-a]isoquinolines, pyrido[2,1-a]isoquinolines, and isoindolo[1,2-a]isoquinolinones in excellent yields. When phthalic acid is used, a workup with either NaBH4 or a saturated NaHCO3 solution provided 12b-H or 12b-OH isoindolo[1,2-a]isoquinolinones, respectively.