Abbiati Giorgio, Arcadi Antonio, Bellinazzi Alessandra, Beccalli Egle, Rossi Elisabetta, Zanzola Simona
Istituto di Chimica Organica Alessandro Marchesini, Facoltà di Farmacia, Università degli Studi di Milano Via Venezian 21, 20133 Milano, Italy.
J Org Chem. 2005 May 13;70(10):4088-95. doi: 10.1021/jo0502246.
[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.
[反应：见正文] 通过几种2-羰基-1-炔丙基吲哚在氨存在下的分子内环化反应实现了吡嗪并[1,2-a]吲哚核的合成。使用微波加热和一系列催化剂对反应条件进行了优化。1-炔基吲哚-2-甲醛的环化反应在标准加热条件下很容易完成，而微波加热有助于缩短反应时间并提高总产率。此外，对微波辐射时间的微调使得两种吡嗪并[1,2-a]吲哚异构体的选择性合成成为可能。从1-炔基-2-乙酰基吲哚和1-炔基-2-苯甲酰基吲哚衍生物出发，以令人满意的产率得到吡嗪并吲哚，TiCl4被证明是首选的催化体系。在这些情况下，微波加热也有助于加快反应速度并提高产率。讨论了无催化与催化反应机理。
