[Zurück]

P. Chen, P. Ma, X. He, D. Svatunek, F. Liu, K. Houk:
"Computational Exploration of Ambiphilic Reactivity of Azides and Sustmann's Paradigmatic Parabola";
Journal of Organic Chemistry, 86 (2021), 8; 13 S.

We examine the theoretical underpinnings of the seminal discoveries by Reiner Sustmann about the ambiphilic nature of Huisgen's phenyl azide cycloadditions. Density functional calculations with ωB97X-D and B2PLYP-D3 reproduce the experimental data and provide insights into ambiphilic control of reactivity. Distortion/interaction-activation strain and energy decomposition analyses show why Sustmann's use of dipolarophile ionization potential is such a powerful predictor of reactivity. We add to Sustmann's data set several modern distortion-accelerated dipolarophiles used in bioorthogonal chemistry to show how these fit into the orbital energy criteria that are often used to understand cycloaddition reactivity. We show why such a simple indicator of reactivity is a powerful predictor of reaction rates that are actually controlled by a combination of distortion energies, charge transfer, closed-shell repulsion, polarization, and electrostatic effects.

Cycloaddition Reaction; Physical Phenomena; Static Electricity; Azides

http://dx.doi.org/10.1021/acs.joc.1c00239

https://publik.tuwien.ac.at/files/publik_303204.pdf