Microwave-Promoted Synthesis of N-Heterocycles by Tandem Imination/Annulation of γ- and δ-Ketoalkynes in the Presence of Ammonia

The synthesis of 3-substituted 1-methylpyrrolo[1,2-a]pyrazines and 3-substituted isoquinolines was achieved by the intramolecular cyclisation of 2-acetyl-1-propargylpyrroles and 2-alkynylbenzaldehydes, respectively, in the presence of ammonia under microwave heating. The tandem imination/annulation of 2-alkynylbenzaldehydes was easily accomplished under standard conditions, while TiCl4 was used to achieve pyrrolo[1,2-a]pyrazines. The reaction mechanism and the regioselectivity were discussed on the basis of theoretical calculations and spectroscopic data. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)