Catalytic Transfer Hydration of Cyanohydrins to α-Hydroxyamides

J Am Chem Soc. 2019 Jan 16;141(2):825-830. doi: 10.1021/jacs.8b12877. Epub 2019 Jan 2.

Abstract

We report the palladium(II)-catalyzed transfer hydration of cyanohydrins to α -hydroxyamides by using carboxamides as water donors. This method enables selective hydration of various aldehyde- and ketone-derived cyanohydrins to afford α-mono- and α,α-disubstituted-α -hydroxyamides, respectively, under mild conditions (50 °C, 10 min). The direct conversion of fenofibrate, a drug bearing a benzophenone moiety, into a functionalized α,α-diaryl-α -hydroxyamide was achieved by means of a hydrocyanation-transfer hydration sequence. Preliminary kinetic studies and the synthesis of a site-specifically 18O-labeled α -hydroxyamide demonstrated the carbonyl oxygen transfer from the carboxamide reagent into the α -hydroxyamide product.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemical synthesis*
  • Amides / chemical synthesis*
  • Catalysis
  • Coordination Complexes / chemistry
  • Fenofibrate / chemistry
  • Models, Chemical
  • Molecular Structure
  • Nitriles / chemistry*
  • Palladium / chemistry

Substances

  • Alcohols
  • Amides
  • Coordination Complexes
  • Nitriles
  • Palladium
  • Fenofibrate