Selective ortho-Functionalization of Adamantylarenes Enabled by Dispersion and an Air-Stable Palladium(I) Dimer

Contrary to the general belief that Pd-catalyzed cross-coupling at sites of severe steric hindrance are disfavored, we herein show that the oxidative addition to C−Br ortho to an adamantyl group is as favored as the corresponding adamantyl-free system due to attractive dispersion forces. This enabled the development of a fully selective arylation and alkylation of C−Br ortho to an adamantyl group, even if challenged with competing non-hindered C−OTf or C−Cl sites. The method makes use of an air-stable Pd^I dimer and enables straightforward access to diversely substituted therapeutically important adamantylarenes in 5–30 min.