Organic compounds with strained, four-membered rings can be useful building blocks in organic synthesis. Benzocyclobutenes, for example, which consist of fused benzene and cyclobutene rings, can undergo a variety of useful transformations. Incorporating a nitrone group (R₂C=N⁺(R’)–O^–) might expand this range further.

Jakub Brześkiewicz and Rafał Loska, Polish Academy of Sciences, Warsaw, Poland, have developed the first protocol for the synthesis of benzocyclobutenone-derived ketonitrones (pictured). The team started from bromoaryl-substituted aldonitrones, which were subjected to a palladium-catalyzed intramolecular C(sp²)–H functionalization to close the four-membered ring. The aldonitrone substrates could be readily obtained from (2-bromophenyl)acetonitriles. The researchers used Pd(OAc)₂ as a catalyst, 1,2-bis(diphenylphosphino)ethane (dppe) as a ligand, Cs₂CO₃ as a base, and toluene as the solvent. The reactions were performed at 100 °C.

The desired benzocyclobutenitrones were obtained in mostly high yields. The reaction tolerates a broad range of electron-withdrawing and electron-donating substituents at the benzene ring, as well as different substituents in α-position to the nitrone group. The products can be used in further transformations, e.g., 1,3-dipolar cycloadditions or nucleophilic additions.

• Palladium-Catalyzed Access to Benzocyclobutenone-Derived Ketonitrones via C(sp2)–H Functionalization,
  Jakub Brześkiewicz, Rafał Loska,
  Org. Lett. 2022.
  https://doi.org/10.1021/acs.orglett.2c01317