Density Functional Theory Determination of an Axial Gateway To Explain the Rate and Endo Selectivity Enhancement of Diels−Alder Reactions by Bis(oxazoline)-Cu(II)

Abstract

A novel conceptual model and unique understanding of rate and endo selectivity enhancements delivered by bis(oxazoline)-Cu(II) Lewis acid catalysts in the Diels-Alder reaction of cyclopentadiene and acrylate imide is presented. Despite previously reported kinetic and spectroscopic studies, the physical reasons for endo selectivity and rate enhancements remain poorly understood. Large-scale density functional calculations using Becke three-parameter density functional theory with the nonlocal correlation of Lee, Yang, and Parr and the 6-31G(d) basis set have been carried out for the first time to understand the geometric and energetic consequences of C(2)-substituent variation. The unique positioning of the tert-butyl C(2)-substituent with respect to the diene, referred to as the "axial gateway", maintains the electrophilicity of the catalyst by shielding the reactive metal center from nucleophilic attack. The interplay between steric and electronic factors is crucial to understanding the observed enhanced rates and endo selectivity.

Diels−Alder Exo Selectivity in Terminal-Substituted Dienes and Dienophiles: Experimental Discoveries and Computational Explanations

“…The activation enthalpies refer to the difference between the enthalpy of the TS and the sum of enthalpies of diene and the dienophile complex infinitely separated in the gas phase. The small and negative gas-phase Δ H ‡ (and the negative Δ E ‡ , see below) values are often observed in modeling gas-phase ion/molecule reactions in general 37, 38. In the present case they are consistent with the more favorable electrostatic attractions expected between the diene's electrons and the cationic A 2 at the TS, compared with the separate, unbound state.…”

Theoretical Studies of Substitutionally Doped Single-Walled Nanotubes

“…We evaluated Lewis acidity based on rate enhancement, as well as selectivity between exo-and endo-products. Although subtle solvent effects have been noted in the literature [224][225][226][227][228][229][230], we did not consider these factors in our calculations.…”

Determination of local effects for chloroaluminate ionic liquids on Diels–Alder reactions

“…The use of density functional theory (DFT) methodology on a small number of explicit cation and anion combinations complexed to the reacting substrates may help elucidate the local interactions responsible for the observed rate acceleration while providing improved thermodynamic agreement with experiment. Representation of solvation effects by discrete models incorporating a few key molecules at specific interacting sites has been successful for other Diels-Alder reactions [14][15][16] , respectively, has been reported to react with rates over 200 times faster and endo selectivity 10 times greater than commonly used reaction conditions. Density functional theory (DFT) calculations at the B3LYP/6-311+G(2d,p) theory level have been employed to determine the origin of the reported rate accelerations.…”