Issue 48, 2021

Chemical reactivity from an activation strain perspective


Chemical reactions are ubiquitous in the universe, they are at the core of life, and they are essential for industrial processes. The drive for a deep understanding of how something occurs, in this case, the mechanism of a chemical reaction and the factors controlling its reactivity, is intrinsically valuable and an innate quality of humans. The level of insight and degree of understanding afforded by computational chemistry cannot be understated. The activation strain model is one of the most powerful tools in our arsenal to obtain unparalleled insight into reactivity. The relative energy of interacting reactants is evaluated along a reaction energy profile and related to the rigidity of the reactants’ molecular structure and the strength of the stabilizing interactions between the deformed reactants: ΔE(ζ) = ΔEstrain(ζ) + ΔEint(ζ). Owing to the connectedness between the activation strain model and Kohn–Sham molecular orbital theory, one is able to obtain a causal relationship between both the sterics and electronics of the reactants and their mutual reactivity. Only when this is accomplished one can eclipse the phenomenological explanations that are commonplace in the literature and textbooks and begin to rationally tune and optimize chemical transformations. We showcase how the activation strain model is the ideal tool to elucidate fundamental organic reactions, the activation of small molecules by metallylenes, and the cycloaddition reactivity of cyclic diene- and dipolarophiles.

Graphical abstract: Chemical reactivity from an activation strain perspective

Article information

Article type
Feature Article
16 Apr 2021
25 May 2021
First published
25 May 2021
This article is Open Access
Creative Commons BY license

Chem. Commun., 2021,57, 5880-5896

Chemical reactivity from an activation strain perspective

P. Vermeeren, T. A. Hamlin and F. M. Bickelhaupt, Chem. Commun., 2021, 57, 5880 DOI: 10.1039/D1CC02042K

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