Bio-inspired NHC-organocatalyzed Stetter reaction in aqueous conditions
Mégane Debiais1,2, Aladin Hamoud1,2, Reihana Drain1,2
1Univ. Bordeaux, CNRS, INSERM, ARNA, UMR 5320, U1212 F-33000 Bordeaux France valerie.desvergnes@u-bordeaux.fr +33 557571176.
Abstract:
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 °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.
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