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.