Direct synthesis of α-trifluoromethyl ketone from (hetero)arylacetylene: design, intermediate trapping, and mechanistic investigations

Org Lett. 2014 Sep 5;16(17):4524-7. doi: 10.1021/ol502071g. Epub 2014 Aug 15.

Abstract

Regioselective addition across the alkynes has been achieved in a silver-catalyzed protocol utilizing Langlois reagent (CF3SO2Na) and molecular O2 to access medicinally active α-trifluoromethyl ketone compounds. This method was successful in producing α-trifluoromethyl ketone in heterocyclic scaffolds, which are incompatible with earlier strategies. Experimental findings suggest a mechanism involving α-styrenyl radical intermediate and 1-methyl-2-pyrrolidinone (NMP) solvent, which leads to crystallographically characterized N-methylsuccinimide. Isotope labeling, kinetic studies, and intermediate trapping further helped to gain insight into this energy-demanding process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Catalysis
  • Combinatorial Chemistry Techniques
  • Ketones / chemical synthesis*
  • Ketones / chemistry
  • Kinetics
  • Molecular Structure
  • Pyrrolidinones / chemistry
  • Solvents
  • Stereoisomerism
  • Succinimides / chemical synthesis
  • Succinimides / chemistry

Substances

  • Alkynes
  • Ketones
  • N-methylsuccinimide
  • Pyrrolidinones
  • Solvents
  • Succinimides
  • N-methylpyrrolidone