Exploring the Regioselectivity of Diels–Alder Reactions of 2,6-Disubstituted Benzoquinones through DFT Calculations

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Authors

KALLA Erik SEMRÁD Hugo MAIER Lukáš PARUCH Kamil ZIPSE Hendrik MUNZAROVÁ Markéta

Year of publication 2025
Type Article in Periodical
Magazine / Source European Journal of Organic Chemistry
MU Faculty or unit

Faculty of Science

Citation
web https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.202500661
Doi https://doi.org/10.1002/ejoc.202500661
Keywords computational chemistry; Diels–Alder reaction; dienes; dienophiles; substituted benzoquinones
Attached files
Description Diels–Alder reactions of 2-methyl-6-substituted-p-benzoquinones are studied using quantum chemical calculations. The effect of 19 substituents, including halomethyl, alkyl, vinyl, ethynyl, nitrile, trifluoromethyl, methoxy, cyclohexenyl, phenyl, and trifluoromethoxyphenyl groups, on the reaction barriers is explored by the B3LYP-D3, M06-2X, and DLPNO-CCSD(T) methods. Gibbs free activation energies are compared for the two regioisomeric products experimentally observed in the reaction mixture. For 75% of the substituents, the calculated barrier difference (?G‡b – ?G‡a) lies within 2.0?kcal?mol-1 of the value determined from the experimentally observed product ratio a/b. Activation barriers are further analyzed in terms of the underlying deformation and interaction energies. The difference in deformation energies of transition states corresponding to the two regioisomers ranges from -8.0 to +8.0?kcal?mol-1 and is directly proportional to experimental ln(a/b) values. Differences in interaction energies between regioisomeric transition states are, in comparison, significantly smaller.
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