Preparation of 2,3-disubstituted indoles by sequential Larock heteroannulation and silicon-based cross-coupling reactions

A simple and convergent synthesis of 2,3-disubstituted indoles has been developed using a sequential Larock indole synthesis and silicon-based, cross-coupling reaction. Substituted 2-iodoanilines reacted with an alkynyldimethylsilyl tert-butyl ether to afford indole-2-silanols under the Larock heteroannulation conditions after hydrolysis. The corresponding sodium 2-indolylsilanolate salts successfully engaged in cross-coupling with aryl bromides and chlorides to afford multi-substituted indoles. The development of an alkynyldimethylsilyl tert-butyl ether as a masked silanol equivalent enabled a smooth heteroannulation process and the identification of a suitable catalyst/ligand combination provided for a facile cross-coupling reaction.