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

Abstract

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.

Keywords: DFT calculations; Diels-Alder reactions; activation strain model; charge transfer; chiral anthracenes.

Scheme 1

Chiral anthracene templates and dienophiles used for DA cycloadditions.

Scheme 2

Cycloaddition reactions studied in this work between a chiral anthracene template ANT and eleven dienophiles 1 A to 3 C. The chiral group in the template is labelled with *. The numbering of the most important atoms in the template and dienophiles is shown.

Figure 1

Qualitative potential energy profile for the DA cycloadditions studied in this work

Figure 2

Transition state structures for the reaction of ANT with dienophiles 1 A–3 C obtained at the M06‐2X/6‐311++G(d,p) level of theory. The bond lengths and hydrogen bond interactions are reported in angstroms (Å). The synchronicity (Δd=|d1−d2|) of the TS is reported in red.

Figure 3

Frontier molecular orbitals (FMO) of the stationary points for the reaction ANT and dienophile 1 A; a) separate reactants; b) reactant complex; c) transition state structure. FMO were obtained at the M06‐2X/TZVP//M06‐2X/6‐311++G(d,p) level of theory. Contour isovalue 0.04 au.

Figure 4

Plot of the CT versus a) the HOMO‐LUMO gap at the TS structures for three groups of dienophiles considered here; b) the HOMO‐LUMO gap at the TS structures of maleic anhydrides 1 A_F, 1 A_Cl, and 1 A_CN. Calculations were performed at the M06‐2X/TZVP//M06‐2X/6‐311++G(d,p) level of theory.

Figure 5

Plot of the a) CT and b) HOMO‐LUMO gap at TS versus the activation energy (ΔE ^≠) for all dienophiles considered here. Calculations were performed at the M06‐2X/TZVP//M06‐2X/6‐311++G(d,p) level of theory.

Figure 6

Plots of the a) total strain energies (ΔE ^≠ _strain) and their components b) the strain energies of the diene and c) the strain energies of the dienophile versus the activation energy (ΔE ^≠); plots of the d) interaction energies (ΔE ^≠ _int) and their components e) the steric repulsion energy and f) the orbital interaction energies versus the activation energy (ΔE ^≠) for the group of maleimides. Calculations were performed at the M06‐2X/TZVP//M06‐2X/6‐311++G(d,p) level of theory.

Figure 7

Plots of the a) interaction energies (ΔE ^≠ _int) and b) strain energies (ΔE ^≠ _strain) versus the activation energy (ΔE ^≠) for the group of acetoxy lactones. The individual components of the strain energies are also shown for c) diene and d) dienophile. Calculations were performed at the M06‐2X/TZVP//M06‐2X/6‐311++G(d,p) level of theory.

Figure 8

Gibbs energy profiles at 298 K (in kcal mol⁻¹) of the DA cycloaddition between ANT and maleic anhydride 1 A, considering a) the two gas phase catalyzed pathways where the Brønsted acid (H⁺) is placed on 1 A (option 1, blue profile) and on ANT (option 2, red profile), and b) the comparison between uncatalyzed and catalyzed reactions in gas phase and solvent. In all cases, the origin of energies are the separate reactants. All calculations were performed at the M06‐2X/6‐311++G(d,p) level of theory.