C-3 functionalization of indoles with methyl 2-acetamidoacrylate under Gold(I), Silver or Brønsted acids catalysis

The chemical modification of indoles through direct functionalization of their C–H bonds constitute a widespread research area of continuous interest for organic synthesis since this scaffold is present in a huge variety of natural product families, medicines or drug candidates, among others. In particular, the formation of a new C–C bond by means of innovative catalytic systems represents an alternative to traditional Friedel-Crafts reactions and allows the use of less toxic reagents and to operate in milder conditions. Among metals, gold catalysts have been employed to this scope in the last years. In our research group, in particular, we get interested in investigating the reactivity of indoles towards α-amidoacrylates, as specific class of enones, in the presence of gold or silver catalysts. Thus, under the optimized reactions conditions we were able to synthetize a series of α- indolylacrilates in high yields. Furthermore an acid-catalyzed version of this reaction was also explored achieving similar results.