Intramolecular Cyclization of delta-Iminoacetylenes: A New Entry to Pyrazino[1,2-a]indoles

The synthesis of the pyrazino[1,2-α]indole nucleus was achieved by intramolecular cyclization of several 2-carbonyl-1-propargylindoles in the presence of ammonia. The reaction conditions were optimized using microwave heating and a pool of catalysts. Cyclization of 1-alkynylindole-2-carbaldehydes was easily accomplished under standard heating conditions, whereas microwave heating contributed to reduced reaction times and improved overall yields. Moreover, a fine-tuning of the microwave irradiation time made possible the selective synthesis of both pyrazino[1,2-α]indole isomers. TiCl4 proved the catalytic system of choice to achieve pyrazinoindoles in satisfactory yields starting from 1-alkynyl-2-acetylindoles and 1-alkynyl-2-benzoylindole derivatives. Also in these cases, microwave heating contributed to faster reactions and improved yields. The uncatalyzed versus catalyzed reaction mechanism is discussed.