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.

Iterative Arylation of Amino Acids and Aliphatic Amines via δ-C(sp3 )-H Activation: Experimental and Computational Exploration.

Directed C-H functionalization has been realized as a complementary tool to the traditional approaches for a straightforward access of non-proteinogenic amino acids; albeit such a process is restricted mostly up to the γ-position. In the present work, we demonstrate the diverse (hetero)arylation of amino acids and analogous aliphatic amines selectively at the remote δ-position by tuning the reactivity controlled by ligands. An organopalladium δ-C(sp3 )-H activated intermediate has been isolated and crystallographically characterized. Mechanistic investigations carried out experimentally in conjunction with computational studies shed light on the difference in the mechanistic picture depending on the substrate structure.