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

A domino condensation-cyclization method is developed to synthesize indolizidine alkaloids using a PO/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-]isoquinolines, pyrido[2,1-]isoquinolines, and isoindolo[1,2-]isoquinolinones in excellent yields. When phthalic acid is used, a workup with either NaBH or a saturated NaHCO solution provided 12-H or 12-OH isoindolo[1,2-]isoquinolinones, respectively.