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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) 2‐Acetyl‐1‐propargylpyrroles and 2‐alkynylbenzaldehydes were demonstrated to be suitable building blocks for the synthesis of pyrrolo[1,2‐a]pyrazine and isoquinoline nuclei. TiCl4 and/or microwave heating efficiently promoted the domino imination/annulation reaction. The mechanism and selectivity were discussed on the basis of computational and spectroscopic data.