Catalytic conjugate additions of carbonyl anions under neutral aqueous conditions.
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.
Myers
Michael C
MC
Department of Chemistry, Northwestern University, Evanston, Illinois 60208, USA.
Bharadwaj
Ashwin R
AR
Milgram
Benjamin C
BC
Scheidt
Karl A
KA
D000478:Alkylation; D000838:Anions / Q000737:chemistry; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013844:Thiazoles / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D000838:Anions; D002264:Carboxylic Acids; D013844:Thiazoles; D014867:Water