Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/119980
Title: Can an alcohol act as an acid/base catalyst in water solution? An experimental and theoretical study of imidazole catalysis of the Morita-Baylis-Hillman reaction
Author: Raich, Lluís
Santos, Hugo
Gomes, Juliana C.
Rodrigues, Jr., Manoel T.
Galaverna, Renan
Eberlin, Marcos N.
Coelho, Fernando
Rovira i Virgili, Carme
Moyano i Baldoire, Albert
Keywords: Catàlisi
Teoria del funcional de densitat
Catalysis
Density functionals
Issue Date: 11-Jan-2018
Publisher: American Chemical Society
Abstract: The formation of carbon−carbon sigma bonds by the organocatalyzed Morita−Baylis−Hillman (MBH) reaction constitutes a convenient method for the synthesis of valuable, highly functionalized molecules. Its large-scale implementation is however hampered both by its poor performance with substrates such as α,β-unsaturated ketones and by the reduction of the nucleophilicity of the catalyst when using water as a solvent. Recent work from our laboratories has shown that a bicyclic imidazolyl alcohol (BIA) overcomes these limitations and is a much more efficient catalyst than imidazole for the aqueous MBH reactions of cyclic enones. The role of the hydroxyl group in the former catalyst is not easy to understand, however, since these reactions take place in water solution. We have studied the mechanism of the aqueous MBH reaction between 2- cyclohexenone and isatin, catalyzed either by imidazole or by the BIA catalyst, using a combined experimental and computational approach. The data allowed us to propose mechanistic free-energy profiles for the two catalysts. An intramolecular proton transfer step, facilitated by the hydroxyl group of the catalyst even if the reaction takes place in water, accounts for the higher catalytic efficiency of BIA in comparison to imidazole, which requires assistance by an external base (either hydroxide ion or another imidazole molecule) for this catalytic step. The computed activation energies are in good agreement with the experimentally observed trends in reaction rates. The crucial role of the BIA hydroxyl has been confirmed by NMR study of the reaction kinetics, and in situ ESI-MS/MS monitoring experiments have detected and characterized all the relevant reaction intermediates, validating the computational model. This study provides clear evidence for the intramolecular participation of a bifunctional catalyst in the proton transfer step of an MBH reaction. The fact that the introduction of a suitable functional group favors the intramolecular proton transfer over solvent-mediated pathways, just in the spirit of enzymatic catalysis, provides a basis for the rational design of future efficient catalysts for aqueous reactions.
Note: Versió postprint del document publicat a: https://doi.org/10.1021/acscatal.7b04053
It is part of: ACS Catalysis, 2018, vol. 8, p. 1703-1714
URI: http://hdl.handle.net/2445/119980
Related resource: https://doi.org/10.1021/acscatal.7b04053
ISSN: 2155-5435
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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