Axially chiral, or atropisomeric, biaryl compounds can be useful, e.g., as ligands in enantioselective catalysis or in drug development. Their chirality is based on the hindered rotation around a σ bond due to the steric hindrance of neighboring groups. Preparing such biaryls from unfunctionalized starting materials via C–H functionalization reactions can be useful, but generally requires directing groups and/or transition-metal catalysts, and existing approaches can have a limited substrate scope.

David A. Nicewicz, University of North Carolina at Chapel Hill, USA, and colleagues have developed a general approach to the coupling of biaryls with a range of nucleophiles to obtain atropisomers using organic photoredox catalysis. The team used an acridinium-based photoredox catalyst (3,6-di-tert-butyl-9-mesityl-10-phenylacridin-10-ium tetrafluoroborate) to react a wide range of biaryl compounds with different nucleophiles, e.g., pyrazole derivatives, nitriles, or amines. The reactions were performed under 427 nm LED light in the presence of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) as a radical initiator and O₂ as an oxidant, using dichloromethane (DCM) as the solvent.

Under these conditions, the desired biaryl atropisomers were obtained in moderate to excellent yields. The method does not require transition-metal catalysts, prior functionalization, or pre-existing directing groups. Overall, the work provides access to a broad range of structurally diverse axially chiral biaryl compounds.

• Synthesis of Biaryl Atropisomers via Site-Selective C–H Functionalization,
  Jason C. Genova, David A. Nicewicz,
  Org. Lett. 2025.
  https://doi.org/10.1021/acs.orglett.5c00121