Nickel-Catalyzed Conversion of Amides to Carboxylic Acids

Org Lett. 2020 Apr 3;22(7):2833-2837. doi: 10.1021/acs.orglett.0c00885. Epub 2020 Mar 25.

Abstract

We report the conversion of amides to carboxylic acids using nonprecious metal catalysis. The methodology strategically employs a nickel-catalyzed esterification using 2-(trimethylsilyl)ethanol, followed by a fluoride-mediated deprotection in a single-pot operation. This approach circumvents catalyst poisoning observed in attempts to directly hydrolyze amides using nickel catalysis. The selectivity and mildness of this transformation are shown through competition experiments and the net-hydrolysis of a complex valine-derived substrate. This strategy addresses a limitation in the field with regard to functional groups accessible from amides using transition metal-catalyzed C-N bond activation and should prove useful in synthetic applications.

Publication types

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

MeSH terms

  • Amides / chemistry*
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / chemistry
  • Catalysis
  • Hydrolysis
  • Molecular Structure
  • Nickel / chemistry*

Substances

  • Amides
  • Carboxylic Acids
  • Nickel