<p>Despite
the widespread applications of C–H functionalization, controlling site
selectivity remains a significant challenge. Covalently attached directing
group (DG) served as an ancillary ligand to ensure proximal <i>ortho</i>-,
distal <i>meta</i>- and <i>para</i>-C-H functionalization over the
last two decades. These covalently linked DGs necessitate two extra steps for a
single C–H functionalization: introduction of DG prior to C–H activation and
removal of DG post-functionalization. We introduce here a transient directing
group for distal C(<i>sp<sup>2</sup></i>)-H
functionalization <i>via</i> reversible
imine formation. By overruling facile proximal C-H bond
activation by imine-<i>N</i> atom, a
suitably designed pyrimidine-based transient directing group (TDG) successfully
delivered selective distal C-C
bond formation. Application of this transient directing group strategy for
streamlining the synthesis of complex organic molecules without any necessary
pre-functionalization at the distal position has been explored.</p>
