Regiospecificity in Ligand-Free Pd-Catalyzed C–H Arylation of Indoles: LiHMDS as Base and Transient Directing Group

A highly efficient catalyst–base pair for the C–H arylation of free (NH)-indoles in the C-3 position is reported. Ligand-free palladium acetate coupled with lithium hexamethyldisilazide (LiHMDS) catalyzed the regiospecific, i.e. 100% regioselective, C-3 arylation of indoles with high turnover numbers. This catalytic system has been successfully applied to a wide range of substrates, including various functional aryl halides and indolic cores. The unique role of LiHMDS as both a base and unexpected transient directing group has been revealed experimentally and elucidated computationally, in line with a Heck-type insertion–elimination mechanism.