Organic Chemistry

Proton Transfer and Kinetic Isotope Effect in Morita-Baylis-Hillman Reaction Under Solvent Effects. a Detailed Computational Study



Solvent effects of CH2Cl2, CH3CN, THF and DMSO on the profile of the Morita-Baylis-Hillman (MBH) reaction were discovered to lower the activation energy of aldol step. Proton-transfer through seven-membered TS state structure enroute Hofmann elimination and also the four-membered TS structure are sufficiently low energy processes in comparison to aldol reaction and, hence, unlikely to contribute to the overall kinetics of the reaction. As an exception, proton-transfer through seven-membered TS structure constitutes the rate-controlling event for the DABCO-catalyzed reaction of methyl acrylate with p-nitrobenzaldehyde under the solvent effects of DMSO. The acetal route was not found to contribute to kinetic isotope effect, which has otherwise been measured to be as high as 5.2 ± 0.6. The simultaneous proton-transfer to the aldol-derived alkoxide and abstraction of proton from the a-carbon of activated alkene by hydroxylic solvents was found to be barrier-less. The reported catalysis by hydroxylic solvents is therefore likely by lowering the activation energy of the aldol step due to activation of aldehyde possibly by protonation or hydrogen-bonding. The present computational results are in excellent agreement with the more than three decade old experimental findings of Hill and Isaacs. These authors have reported the aldol step as rate-limiting and absolutely no kinetic isotope effect.


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Supplementary material

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