Imine as a linchpin approach for meta-C-H functionalization

Despite the widespread applications of C-H functionalization, controlling site selectivity remains a significant challenge. Covalently attached directing groups (DGs) served as ancillary ligands to ensure ortho-, meta- and para-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. Here we report a temporary directing group (TDG) for meta-C-H functionalization via reversible imine formation. By overruling facile ortho-C-H bond activation by imine-N atom, a suitably designed pyrimidine-based TDG successfully delivered selective meta-C-C bond formation. Application of this temporary directing group strategy for streamlining the synthesis of complex organic molecules without any necessary pre-functionalization at the meta position has been explored. Site-selective C-H functionalization still faces some challenges, such as the introduction and removal of an appropriate directing group. Here, the authors introduce a temporary directing group for selective meta-C-H functionalization of 2-arylbenzaldehydes via reversible imine formation.

Automated summary

Despite the widespread use of C-H functionalization, controlling site selectivity remains a challenge. Researchers have introduced a temporary directing group for selective meta-C-H functionalization via reversible imine formation, which can streamline the synthesis of complex organic molecules.