Atroposelective Diverse Remote meta-C-H Functionalization via Kinetic Resolution

A diverse range of Pd(II)-catalyzed enantioselective C-H activation reactions have been developed to construct point, axial, and planar chirality. Despite the importance of chiral biaryl scaffolds in bioactive molecules and chiral ligands, atroposelective functionalization at the meta-position remains a significant challenge. Here, we realized a rare atroposelective remote meta-C-H functionalization with a chiral monoprotected amino acid (MPAA) ligand and a racemic transient norbornene mediator. The reaction starts with enantioselective ortho-C-H activation via kinetic resolution to give a chiral biaryl-palladium intermediate, which subsequently undergoes a Catellani relay to afford chiral meta-functionalized biaryl products (S-factors up to 458). The obtained diverse enantioenriched quinoline-based atropisomers are ubiquitous in natural products, pharmaceuticals, chiral ligands, and functional materials. Moreover, unprecedented enantioselective meta-alkenylation and alkynylation have also been developed using this approach. A wide range of synthetic applications of the chiral 8-aryl quinolines, including the synthesis of novel P,N-ligand and chiral functional materials with CPL activity, have been demonstrated.