Reactions of β-alkoxyvinyl polyfluoroalkyl ketones with ethyl isocyanoacetate and its use for the synthesis of new polyfluoroalkyl pyrroles and pyrrolidines

Org Biomol Chem. 2012 Nov 28;10(44):8778-85. doi: 10.1039/c2ob26176f.

Abstract

The hitherto unreported reactions of β-alkoxyvinyl polyfluoroalkyl ketones with ethyl isocyanoacetate and equimolar amounts of potassium-tert-butoxide proceeded mainly in the β-position of the α,β-unsaturated ketones in cases of α-nonsubstituted 1a–e and α-methyl substituted ketones 1g–j. Other α- or β-substituted ketones 1f,k–o gave mainly products 4 of initial attack at the carbonyl carbon. Depending on the solvent, the major products of β-attack do exist in different tautomeric forms. Generally the openchain enol tautomers 5 predominate in the polar DMSO-d(6), while the cyclic γ-hemiaminals 8 are the major tautomers in the less polar CDCl(3). Acid treatment of the latter compounds 8 led to the hitherto unknown ethyl 5-polyfluoroalkyl-pyrrole-2-carboxylates 11 by elimination of formic acid. Catalytic hydrogenation of pyrrole 11a was used for the synthesis of earlier unknown 5-trifluoromethyl proline 16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemical synthesis
  • Acetates / chemistry*
  • Catalysis
  • Hydrogenation
  • Ketones / chemical synthesis
  • Ketones / chemistry*
  • Models, Molecular
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / chemistry
  • Stereoisomerism

Substances

  • Acetates
  • Ketones
  • Pyrroles
  • Pyrrolidines