Catalytic Conjugate Additions of Carbonyl Anions under Neutral Aqueous Conditions

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 α-keto carboxylates and thiazolium-derived zwitterions produces reactive carbonyl anions in a buffered protic environment that readily undergo conjugate additions to substituted α,β-unsaturated 2-acyl imidazoles. The scope of the reaction has been examined and found to accommodate various α-keto carboxylates and β-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.