Atroposelective remote meta-C–H activation

Axially chiral motifs are prominent in chiral ligands and catalysts, natural products, and drug candidates. Consequently, new strategies for the expedient stereoselective preparation of axially chiral scaffolds would have wide-ranging impacts. Here, we report a highly atroposelective remote meta-C–H arylation of 2-arylanilines employing an enantioselective palladation relay strategy using a chiral norbornene [(+)-NBE-CO2Me] transient mediator for the preparation of distally substituted axially chiral scaffolds. This method provides a highly efficient route toward meta-substituted, axially chiral anilines. The cooperative palladium/norbornene catalytic system features the use of native aniline directing groups, broad substrate scope, high stereoinduction (S factor up to 167), and excellent scalability. The enantioenriched anilines are readily transformed into a diversity of chiral compounds, including chiral ligands and catalysts. Evaluation of an axially chiral meta-substituted ligand in two model catalytic reactions illustrates the potential of our C–H activation method to access valuable new chemical space.