Synthesis of Highly Substituted Indoles via an Intramolecular Heck Cyclization

Significance

A combined multi-component Ugi-Smiles reaction followed by a Heck cyclization for the synthesis of substituted indole derivatives in good to high yield has been developed. Thus the Ugi-Smiles reaction of o-iodophenols, aldehydes, isocyanides and allyl amines gives highly functionalized aniline derivatives which, under Pd-catalyzed cyclization followed by isomerization, yield the highly substituted indoles. Furthermore, hydroxy pyrimidines were found to give indolopyrimidines by the corresponding reactions. Both reactions were successfully carried out in one-pot, with the addition of trifluoroacetic acid (0.2-0.3 equiv to affect the hydrolysis of the remaining isocyanide) before Heck cyclization.