New synthetic method for indole-2-carboxylate and its application to the total synthesis of duocarmycin SA.

The sequential coupling and cyclization reactions between aryl halides and methyl propiolate were investigated. The electron-withdrawing groups on the aromatic ring are essential for producing the methyl indole-2-carboxylate derivatives. On the other hand, the presence of an extra methyl propiolate and Pd(PPh3)4 were required to provide an efficient catalytic system for the cyclization reactions. This reaction was used for the total synthesis of duocarmycin SA. Copyright 2004 American Chemical Society