Palladium-Catalyzed Stitching of 1,3-C(sp3)-H Bonds with Dihaloarenes: Short Synthesis of (±)-Echinolactone D

Martin Tomanik, Jin Quan Yu

Research output: Contribution to journalArticlepeer-review


Palladium-catalyzed C(sp3)-H functionalization presents an efficient strategy to construct a variety of carbon-carbon bonds. However, application of this approach toward the preparation of five-membered benzo-fused carbocycles via the most simplifying C-H activation logic has not been realized. In this Article, we report a palladium-catalyzed annulation reaction between gem-dimethyl-containing amides and 1-bromo-2-iodoarenes that effectively constructs two Calkyl-Caryl bonds and provides access to a variety of five-membered benzo-fused compounds. In this transformation, the dihaloarene is stitched to the gem-dimethyl moiety via two sequential β-C(sp3)-H arylations utilizing the differential reactivity of the 1,2-difunctionalized electrophile. This annulation reaction is enabled by a dual-ligand system comprising of an N-acyl glycine and a pyridine-3-sulfonic acid that synergistically promotes the palladium stitching and provides the bicyclic products. This method displays a broad substrate scope and shows excellent amide compatibility. We also demonstrate the synthetic potential of this annulation by synthesizing echinolactone D.

Original languageEnglish (US)
Pages (from-to)17919-17925
Number of pages7
JournalJournal of the American Chemical Society
Issue number32
StatePublished - Aug 16 2023

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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