Total synthesis of hibispeptin A via Pd-catalyzed C(sp3)-H arylation with sterically hindered aryl iodides

Org Lett. 2014 Dec 19;16(24):6488-91. doi: 10.1021/ol503347d. Epub 2014 Dec 9.


To access the key Ile-Hpa pseudodipeptide motif in hibispeptins, a series of bidentate carboxamide-based auxiliary groups have been explored to facilitate the palladium-catalyzed arylation of unactivated γ-C(sp(3))-H bonds of Ile precursor with aryl iodides. A new pyridylmethylamine-based auxiliary group PR is introduced, which permits the use of more sterically hindered ortho-substituted aryl iodide substrates and can be removed under mild conditions. Pd-catalyzed PR-directed γ-C(sp(3))-H arylation enabled the first total synthesis of hibispeptin A.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Catalysis
  • Hibiscus / chemistry*
  • Hydrogen Bonding
  • Iodides / chemistry*
  • Molecular Structure
  • Palladium / chemistry
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / isolation & purification
  • Plant Roots / chemistry*


  • Iodides
  • Peptides, Cyclic
  • hibispeptin A
  • Palladium