Bio-inspired NHC-organocatalyzed Stetter reaction in aqueous conditions

The first bio-inspired N-Heterocyclic Carbene (NHC)-catalyzed Stetter reaction in aqueous medium is reported with benzaldehyde and chalcone as model substrates. A screening of azolium salts as precatalysts revealed the remarkable efficiency of synthetic thiazolium salt 8 (up to 90% conversion in pure water at 75 degrees C). The reaction was successfully extended to various simple aldehyde substrates. The effect of temperature was also investigated in order to extend the reaction to lower temperature allowing a potential application to sensitive biomolecules. This study highlighted the influence of both solvent and temperature on the 1,4-diketone 3/benzoin 4 ratio. New precatalysts 26 and 27 were designed and synthesized to explore a possible compartmentalization of the reaction in aqueous conditions. Owing to the use of inexpensive metal-free N-Heterocyclic Carbene (NHC) as a bioinspired catalyst, we anticipate that this green strategy in aqueous conditions will be attractive for bioconjugation of many biomolecule-type aldehydes and enone derivatives.