Palladium-Catalyzed Site-Selective Fluorination of Unactivated C(sp(3))-H Bonds

Org Lett. 2015 Aug 7;17(15):3738-41. doi: 10.1021/acs.orglett.5b01710. Epub 2015 Jul 24.

Abstract

The transition-metal-catalyzed direct C-H bond fluorination is an attractive synthetic tool toward the preparation of organofluorines. While many methods exist for the direct sp(3) C-H functionalization, site-selective fluorination of unactivated sp(3) carbons remains a challenge. Direct, highly site-selective and diastereoselective fluorination of aliphatic amides via a palladium-catalyzed bidentate ligand-directed C-H bond functionalization process on unactivated sp(3) carbons is reported. With this approach, a wide variety of β-fluorinated amino acid derivatives and aliphatic amides, important motifs in medicinal and agricultural chemistry, were prepared with palladium acetate as the catalyst and Selectfluor as the fluorine source.

Publication types

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

MeSH terms

  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry
  • Catalysis
  • Fluorine / chemistry*
  • Halogenation
  • Hydrocarbons, Fluorinated / chemical synthesis*
  • Hydrocarbons, Fluorinated / chemistry
  • Molecular Structure
  • Palladium / chemistry*

Substances

  • Amino Acids
  • Hydrocarbons, Fluorinated
  • Fluorine
  • Palladium