Intramolecular cyclization of delta-iminoacetylenes: a new entry to pyrazino[1,2-a]indoles.
[reaction: see text] The synthesis of the pyrazino[1,2-a]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-a]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.
Abbiati
Giorgio
G
Istituto di Chimica Organica Alessandro Marchesini, Facoltà di Farmacia, Università degli Studi di Milano Via Venezian 21, 20133 Milano, Italy. giorgio.abbiati@unimi.it
Arcadi
Antonio
A
Bellinazzi
Alessandra
A
Beccalli
Egle
E
Rossi
Elisabetta
E
Zanzola
Simona
S