Catalytic conjugate additions of carbonyl anions under neutral aqueous conditions

J Am Chem Soc. 2005 Oct 26;127(42):14675-80. doi: 10.1021/ja0520161.

Abstract

The conjugate addition of carbonyl anions catalyzed by thiazolium salts that is fully operative under neutral aqueous conditions has been accomplished. The combination of alpha-keto carboxylates and thiazolium-derived zwitterions produces reactive carbonyl anions in a buffered protic environment that readily undergo conjugate additions to substituted alpha,beta-unsaturated 2-acyl imidazoles. The scope of the reaction has been examined and found to accommodate various alpha-keto carboxylates and beta-aryl substituted unsaturated 2-acyl imidazoles. The optimal precatalyst for this process is the commercially available thiazolium salt 5, a simple analogue of thiamin diphosphate. In this process, no benzoin products from carbonyl anion dimerization are observed. The corresponding 1,4-dicarbonyl compounds can be efficiently converted into esters and amides by way of activation of the N-methylimidazole ring via alkylation.

Publication types

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

MeSH terms

  • Alkylation
  • Anions / chemistry
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / chemistry
  • Catalysis
  • Molecular Structure
  • Oxidation-Reduction
  • Thiazoles / chemistry*
  • Water / chemistry

Substances

  • Anions
  • Carboxylic Acids
  • Thiazoles
  • Water