Cycloaddition Reactivities Analyzed by Energy Decomposition Analyses and the Frontier Molecular Orbital Model

Abstract

Metrics & MoreArticle Recommendations * sı Supporting Information CONSPECTUS: This Account describes our quest to understand and predict organic reactivity, a principal goal of physical and theoretical organic chemistry.The focus is on the development and testing of models for the prediction of cycloaddition reactivities and selectivities. We describe the involvement of the Houk group, and other groups, in the evolution of theoretical models that can achieve ever greater accuracy as well as provide practical heuristic models for understanding and prediction. Is the venerable frontier molecular orbital (FMO) model, the basis of Kenichi Fukui's 1981 Nobel Prize, still useful, or must it be replaced with more advanced models? In particular, models such as Conceptual Density Functional, the Pauli Exclusion Model, and the recent popularity of Electrostatic Potential Plots and Dispersion Energies have not only added to our understanding, but they have also created uncertainty about whether the simple FMO heuristic model has a place in 21st century discussions. This Account addresses this issue and asserts the value of the FMO model. Beginning with brief descriptions of selected models for cycloaddition reactivity starting with early donor−acceptor (nucleophile− electrophile) charge-transfer concepts, this Account reviews Fukui's frontier molecular orbital model, Salem and Klopman's orbital, electrostatic and Pauli repulsion model, the conceptual DFT model by Parr and later by Domingo and others, the recent Houk and Bickelhaupt Distortion/Interaction Activation Strain model, and the Bickelhaupt-Hamlin's Pauli-repulsion lowering model. Computations and analyses of four well-studied Diels−Alder cycloadditions, both normal and inverse electron-demand types, are presented. Most were studied earlier in our published work but are presented here with new insights from calculations with modern methods.Depending on the types of substrates (cycloaddends), the dominant factors controlling reactivity can be orbital interactions, electrostatics and polarization, or Pauli repulsion and dispersion effects, or a combination of all of these. By comparing orbital interactions, especially the frontier molecular orbital interactions, with the other factors that influence reactivity, we show why the FMO model is such a powerful�and theoretically meaningful�heuristic for understanding and predicting reactivity. We also present a method to understand Pauli repulsion effects on activation barriers, ρ(1.1). The use of a new reaction coordinate, the extent of Pauli repulsion along the reaction path, is advocated to emphasize the role of repulsive occupied orbital interactions on reactivity. Fukui's frontier molecular orbital model is effective because FMO interactions parallel all the quantities that influence reactivity. The FMO model continues to provide a practical model to understand and guide experiments.

Pericyclic or Pseudopericyclic? Deep Mechanism Insight into The Mi-gration Selectivity of Cb-Substituted-4aH-Carbazoles: Competition between Orbital Interaction and Electrostatic Interaction

“…Should these migration reactions be regarded as [1, 2n+1] suprafacial sigamatropic rearrangement 10 (pericyclic) or nucleophilic addition of the migrating group R to imines (pseudopericyclic)? NPA charge 11 and FMO 12 analyze on substrates TFA-6 have been conducted (Fig. 4B/C), showing that C 4 have more HOMO distributions whereas C a have more positive NPA charges and LUMO distributions.…”

Understanding chemistry: from “heuristic (soft) explanations and reasoning by analogy” to “quantum chemistry”

“…These reactions depend on geometry, strain, electrostatics and polarization, Pauli repulsion and dispersion effects as well as orbital symmetry factors. 121 [2 + 2] cycloadditions are fine thermallyif the appropriate orbital symmetry-required geometries can be achieved and a high energy barrier can be overcome, or if the substituents cause significant asymmetry and the reaction proceeds by a non-Woodward-Hoffmann pathway. [122][123][124] (bottom) Examples of valence isomerizations in vitamin D chemistry.…”

Strain-Release Controlled [4+2+1] Reaction of Cyclopropyl-Capped Diene-Ynes/Diene-enes and CO Catalyzed by Rhodium

“…8a Here we used quantum chemistry calculations to support that CP diene is more active than dimethyl-diene in D-A reaction with maleic anhydride, by also about 7 kcal/mol in terms of activation free energy, due to the strain release (Scheme 3, reactions c and d). A quantitative understanding of this strain release can use distortion-interaction model 20 , indicating that distortion of MCP in the CP-diene is much less than dimethyl-diene by 11.4 kcal/mol in the [4+2] reaction, whereas interaction energy is nearly identical for both (9.3 vs. 9.4 kcal/mol) (reactions c and d, Scheme 3 and see the Supporting Information).…”