Copper(II)-Catalyzed Direct C-H (Hetero)arylation at the C3 Position of Indoles Assisted by a Removable N,N-Bidentate Auxiliary Moiety

The regioselective arylation of inert C3-H bonds in indoles reacting with arylboronates via effective copper-mediated catalysis with the aid of a facile and removable 2-pyridinylisopropyl (PIP) group without ligand participation is reported. This newly established method features high compatibility with diverse functional groups between coupling partners, including both indole substrates and arylboron reagents, consequentially leading to operational simplicity and providing access to generate the desired arylated products in good to excellent yields of up to 97%. Synthetically, the PIP-derived amide moiety could subsequently be readily removed under mild reaction conditions to produce useful indole carboxylic acids for further transformation.

Automated summary

A newly established method for the regioselective arylation of inert C3-H bonds in indoles using effective copper-mediated catalysis with the aid of a removable PIP group is reported. The method shows high compatibility with functional groups between coupling partners, leading to simplicity in operation and yielding desired arylated products in good to excellent yields up to 97%. Additionally, the PIP-derived amide moiety can be easily removed under mild reaction conditions to produce useful indole carboxylic acids for further transformation.