The evaluation of chemoselectivity in multicomponent domino Knoevenagel/Diels–Alder reaction: A DFT study Scientific paper

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Mina Attarbashi
Nader Zabarjad Shiraz
Marjaneh Samadizadeh


Herein, the chemoselectivity of the multicomponent domino Kno­eve­nagel/Diels–Alder reaction is investigated in terms of theoretical calcu­lations. The structures of reagents, transition states, intermediates and products are optimized at the M062X/6-31+G(d,p) level of theory. The reaction mechanism involves processes of bond rotation, isomerization, asymmetric cycloaddition, acid–base and nucleophile–electrophile competitions, which are studied for the purpose of delivering a clear information of the mechanism in terms of chemo­selectivity considerations. Accordingly, the chemoselectivity of the reaction is controlled by the releasing acetone during the decomposition of Meldrum acid in the presence of methanol and l-proline (DG# = 61.45 kcal** mol-1). Com­paring calculated results (gas and solvent phase) with the experimental ones showed that using these reagents are the kinetical favourite path for the chemo­selective multicomponent cascade Knoevenagel/Diels–Alder reaction to pro­duce the predominant product (>95 %). The results suggest that the creation of cis-spiro cyclohexanone is the predominant chemoselective product under kin­etic control of the desired enone.


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M. Attarbashi, N. Z. Shiraz, and M. . Samadizadeh, “The evaluation of chemoselectivity in multicomponent domino Knoevenagel/Diels–Alder reaction: A DFT study: Scientific paper”, J. Serb. Chem. Soc., vol. 86, no. 11, pp. 1053–1065, Nov. 2021.
Theoretical Chemistry


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