Catalyst-Controlled Regioselectivity in Pd-Catalyzed Aerobic Oxidative Arylation of Indoles

Pd-catalyzed C-H arylation of heteroarenes is an important and widely studied synthetic transformation; however, the regioselectivity is often substrate-controlled. Here, we report catalyst-controlled regioselectivity in the Pd-catalyzed oxidative coupling of N-(phenylsulfonyl)indoles and aryl boronic acids using O-2 as the oxidant. Both C2- and C3-arylated indoles are obtained in good yield with >10:1 selectivity. A switch from C2 to C3 regioselectivity is achieved by adding 4,5-diazafluoren-9-one or 2,2'-bipyrimidine as an ancillary ligand to a "ligand-free" Pd(OTs)(2) catalyst system. Density functional theory calculations indicate that the switch in selectivity arises from a change in the mechanism, from a C2-selective oxidative-Heck pathway to a C3-selective C-H activation/reductive elimination pathway.