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 O2 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.