Switch From Pauli-Lowering to LUMO-Lowering Catalysis in Brønsted Acid-Catalyzed Aza-Diels-Alder Reactions

Song Yu, F. Matthias Bickelhaupt*, Trevor A. Hamlin

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Brønsted acid-catalyzed inverse-electron demand (IED) aza-Diels-Alder reactions between 2-aza-dienes and ethylene were studied using quantum chemical calculations. The computed activation energy systematically decreases as the basic sites of the diene progressively become protonated. Our activation strain and Kohn-Sham molecular orbital analyses traced the origin of this enhanced reactivity to i) “Pauli-lowering catalysis” for mono-protonated 2-aza-dienes due to the induction of an asynchronous, but still concerted, reaction pathway that reduces the Pauli repulsion between the reactants; and ii) “LUMO-lowering catalysis” for multi-protonated 2-aza-dienes due to their highly stabilized LUMO(s) and more concerted synchronous reaction path that facilitates more efficient orbital overlaps in IED interactions. In all, we illustrate how the novel concept of “Pauli-lowering catalysis” can be overruled by the traditional concept of “LUMO-lowering catalysis” when the degree of LUMO stabilization is extreme as in the case of multi-protonated 2-aza-dienes.

Original languageEnglish
Pages (from-to)784-789
Number of pages6
Issue number8
Early online date5 Aug 2021
Publication statusPublished - Aug 2021

Bibliographical note

Funding Information:
This work was supported by the Netherlands Organization for Scientific Research (NWO) and the China Scholarships Council (CSC), and carried out on the Dutch national e‐infrastructure with the support of SURF Cooperative. We thank Pascal Vermeeren for helpful discussions.

Publisher Copyright:
© 2021 The Authors. Published by Wiley-VCH GmbH


  • activation strain models
  • azadienes
  • density functional calculations
  • Diels-Alder reactions
  • reactivity


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