Probing the Mechanism of Classical and the Supramolecular Co-Catalyzed Baylis-Hillman Reactions via ESI(+)-MS and MS/MS

L. S. Santos,* C. H. Pavam, C. S. Consorti, B. A. S. Neto, F. Coelho, J. Dupont and M. N. Eberlin

*University of Oldenburg, Department of Chemistry, D-26111 Oldenburg, Germany

*

The Baylis–Hillman reaction has recently emerged as extremely versatile method for the synthesis of highly complex systems. The reaction leads to the straightforward formation of new  C-C bonds in a single step, and yields functionalized molecules (-methylene--hydroxy derivatives), which are then conveniently manipulated as key synthons in the synthesis of a variety of natural and nonnatural products. In the current work, the proposed intermediates for the catalytic cycle of the Baylis–Hillman reaction (Scheme 1) have been successfully intercepted and structurally characterized for the first time using electrospray ionization with mass and tandem mass spectrometry. Strong evidence for the currently accepted mechanism has been collected, thus confirming the proposals initially made by Isaacs and Hill.[1] Herein, attempts to intercept key cationic intermediates of Baylis–Hillman reactions performed in ionic liquids have been obtained. Several H-bonded cationic species formed by ion pairing of the aldehyde and zwiterionic intermediates with ionic liquid cations and anions have been transferred from solution to the gas-phase, detected and characterized. These supramolecular species indicate therefore that ionic liquids improve overall reaction rates by activating the aldehyde toward nucleofilic attack and by stabilizing the zwitterionic species that acts as the main Baylis-Hillman intermediates.[2]

Scheme 1: Baylis-Hillman reaction of methyl acrylate (1) and thiazolecarboxaldehyde 2 co-catalyzed by both DABCO (3) and ionic liquids BMI.Y (Y-=BF4-, PF6-, CF3CO2-) showing both the protonated and supramolecular H-bonded cationic species gently transferred from solution to the gas phase by ESI, detected and structurally characterized by MS and MS/MS analysis, with their respective m/z ratios.

[[1]] Hill, J. S., Isaacs, N. S. J. Phys. Org. Chem.1990, 3, 285.

[[2]] (a) Santos, L. S., Pavam, C. H., Almeida, W. P., Coelho, F., Eberlin, M. N Angew. Chem. Int. Ed.2004, 43, 4330. (b) Santos, L. S., Pavam, C. H., Consorti, C. S., da Silveria Neto, B. A., Coelho, F., Dupont, J., Eberlin, M. N. Chemistry- A European Journal 2005, submmited.