A synthesis of pyrazino[1,2-a]indoles via one-pot cascade Ugi condensation and N-annulation under mild conditions

Abstract A novel, one-pot, mild and operationally simple synthetic approach for the synthesis of pyrazino[1,2-a]indole derivatives is reported. The reaction proceeds via a 4-component Ugi condensation followed by N-annulation of the intermediate to afford the titled product under metal and acid-free conditions in methanol. The procedure consists of one-step tandem condensation and cyclization of Indole-2-carboxylic acid with isocyanides, phenacylamine hydrochloride and a variety of aromatic aldehydes. This method provides simple access to a wide range of pyrazino[1,2-a]indole derivatives in good to excellent yields under ambient temperature.