Hydroxylation reactions of aromatic compounds are important in organic synthesis. Such hydroxylations of aryl C–H bonds can be performed using transition-metal catalysts. However, this is difficult when molecular oxygen is used as the oxidant.

Jin-Quan Yu, The Scripps Research Institute, La Jolla, CA, USA, and colleagues have developed a protocol for the directed C‒H hydroxylation of both aromatic and heteroaromatic carboxylic acids with molecular oxygen. The team used a palladium complex with a bidentate pyridine-pyridone ligand that efficiently catalyzes this reaction at positions adjacent to carboxylic acids. They converted a variety of aromatic and heterocyclic carboxylic acids using Pd(OAc)₂ as the catalyst, 6-(1-cyclohexyl-1-(5-methylpyridin-2-yl)ethyl)pyridin-2(1H)-one as the ligand, 1,4-benzoquinone as an additive, dimethylformamide (DMF) as the solvent, and O₂ as the oxidant.

The desired hydroxylated products were obtained in mostly good yields. According to the researchers, the ligand binds to the Pd through the pyridine and pyridone components, and a tautomerization reaction involving the ligand leads to two different coordination modes that play a role in the catalytic cycle. The reaction allows the late-stage hydroxylation of complex molecules at sites that were previously difficult to access.

• A tautomeric ligand enables directed C‒H hydroxylation with molecular oxygen,
  Zhen Li, Zhen Wang, Nikita Chekshin, Shaoqun Qian, Jennifer X. Qiao, Peter T. Cheng, Kap-Sun Yeung, William R. Ewing, Jin-Quan Yu,
  Science 2021.
  https://doi.org/10.1126/science.abg2362