Atroposelective remote meta-C-H activation

Axially chiral motifs are prominent in chiral ligands and catalysts, natural products, and drug candidates. Consequently, new strate-gies for the expedient stereoselective preparation of axially chiral scaffolds would have wide-ranging impacts. Here, we report a high-ly atroposelective remote meta-C-H arylation of 2-arylanilines em-ploying an enantioselective palladation relay strategy using a chiral norbornene [(+)-NBE-CO2Me] transient mediator for the prepara-tion of distally substituted axially chiral scaffolds. This method pro-vides 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 scal-ability. 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.

Automated summary

In this study, a highly selective remote meta-C-H arylation strategy was reported for the preparation of distally substituted axially chiral scaffolds using a chiral norbornene as a transient mediator. This method provides an efficient route to meta-substituted, axially chiral anilines with broad substrate scope, high stereoinduction, and scalability. The enantioenriched anilines can be readily transformed into diverse chiral compounds, including chiral ligands and catalysts.