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 PdI dimer and enables straightforward access to diversely substituted therapeutically important adamantylarenes in 5-30 min.