Aqueous Titanium Trichloride Promoted Reductive Cyclization of o-Nitrostyrenes to Indoles: Development and Application to the Synthesis of Rizatriptan and Aspidospermidine

Treatment of o-nitrostyrenes with aqueous TiCl3 solution at room temperature afforded indoles through a formal reductive C(sp(2))-H amination process. A range of functions such as halides (Cl, Br), carbonyl (ester, carbamate), cyano, hydroxy, and amino groups were tolerated. From beta,beta-disubstituted o-nitrostyrenes, 2,3-disubstituted indoles were formed by a domino reduction/cyclization/migration process. Mild conditions, simple experimental procedure, ready accessibility of the starting materials and good to excellent yields characterize the present transformation. The methodology was used as a key step in a concise synthesis of rizatriptan and a formal total synthesis of aspidospermidine.