Rationalizing the Substituent Effects in Diels-Alder Reactions of Triazolinediones with Anthracene.

In this work we tackle the problem of the substituent effects in the Diels-Alder cycloadditions between triazolinediones (TADs) and anthracene. Experiments showed that aryl TADs substituted with electron-withdrawing groups (EWG) are more reactive than those substituted with electron-donating (EDG) or alkyl groups. However, the molecular origin of this preference is not yet understood. By a combination of methods including the activation strain model (ASM), energy decomposition analysis (EDA), molecular orbital (MO) theory, and conceptual density functional theory (CDFT), we disclosed the substituent effects of TADs. First, ASM/EDA analysis revealed that the reactivity of alkyl and aryl-substituted TADs is controlled by interaction energies, ΔEint, which are ultimately defined by orbital interactions between frontier molecular orbitals. Moreover, alkyl-TADs are also controlled by the extent of strain at the transition state. The MO analysis suggested that the rate acceleration for EWG-substituted TADs is due to a more favorable orbital interaction between the HOMO of anthracene and the LUMO of the TADs, which is corroborated by calculations of charge transfer at the transition states. From CDFT, the chemical potential of anthracene is higher than those of TADs, indicating a flow of electron density from anthracene to TADs, in agreement with the results from the electrophilicity index.

Diels-Alder Reactivity of a Chiral Anthracene Template with Symmetrical and Unsymmetrical Dienophiles: A DFT Study.

In this work, we used Density Functional Theory calculations to assess the factors that control the reactivity of a chiral anthracene template with three sets of dienophiles including maleic anhydrides, maleimides and acetoxy lactones in the context of Diels-Alder cycloadditions. The results obtained here (at the M06-2X/6-311++G(d,p) level of theory) suggest that the activation energies for maleic anhydrides and acetoxy lactones are dependent on the nature of the substituent in the dienophile. Among all studied substituents, only -CN reduces the energy barrier of the cycloaddition. For maleimides, the activation energies are independent of the heteroatom of the dienophile and the R group attached to it. The analysis of frontier molecular orbitals, charge transfer and the activation strain model (at the M06-2X/TZVP level based on M06-2X/6-311++G(d,p) geometries) suggest that the activation energies in maleic anhydrides are mainly controlled by the amount of charge transfer from the diene to the dienophile during cycloaddition. For maleimides, there is a dual control of interaction and strain energies on the activation energies, whereas for the acetoxy lactones the activation energies seem to be controlled by the degree of template distortion at the transition state. Finally, calculations show that considering a catalyst on the studied cycloadditions changes the reaction mechanism from concerted to stepwise and proceed with much lower activation energies.