Complex Polyheterocycles and the Stereochemical Reassignment of Pileamartine A via Aza-Heck Triggered Aryl C-H Functionalization Cascades

  • J Am Chem Soc. 2021 Sep 29;143(38):15593-15598. doi: 10.1021/jacs.1c08615.
Benjamin T Jones  1 ,  Javier García-Cárceles  1 ,  Lewis Caiger  1 ,  Ian R Hazelden  1 ,  Richard J Lewis  2 ,  Thomas Langer  3 ,  John F Bower  4
Affiliations
  • 1. School of Chemistry, University of Bristol, Bristol, BS8 1TS, United Kingdom.
  • 2. Department of Medicinal Chemistry, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, SE 43183 Mölndal, Sweden.
  • 3. Chemical Development, Pharmaceutical Technology & Development, Operations, Astra Zeneca, Charter Way, Macclesfield, SK10 2NA, United Kingdom.
  • 4. Department of Chemistry, University of Liverpool, Crown Street, Liverpool, L69 7ZD, United Kingdom.
PMID: 34546043 DOI: 10.1021/jacs.1c08615
Abstract

Structurally complex benzo- and spiro-fused N-polyheterocycles can be accessed via intramolecular Pd(0)-catalyzed alkene 1,2-aminoarylation reactions. The method uses N-(pentafluorobenzoyloxy)carbamates as the initiating motif, and this allows aza-Heck-type alkene amino-palladation in advance of C-H palladation of the aromatic component. The chemistry is showcased in the first total synthesis of the complex alkaloid (+)-pileamartine A, which has resulted in the reassignment of its absolute stereochemistry.

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