How Dihalogens Catalyze Michael Addition Reactions

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

We have quantum chemically analyzed the catalytic effect of dihalogen molecules (X2=F2, Cl2, Br2, and I2) on the aza-Michael addition of pyrrolidine and methyl acrylate using relativistic density functional theory and coupled-cluster theory. Our state-of-the-art computations reveal that activation barriers systematically decrease as one goes to heavier dihalogens, from 9.4 kcal mol−1 for F2 to 5.7 kcal mol−1 for I2. Activation strain and bonding analyses identify an unexpected physical factor that controls the computed reactivity trends, namely, Pauli repulsion between the nucleophile and Michael acceptor. Thus, dihalogens do not accelerate Michael additions by the commonly accepted mechanism of an enhanced donor–acceptor [HOMO(nucleophile)–LUMO(Michael acceptor)] interaction, but instead through a diminished Pauli repulsion between the lone-pair of the nucleophile and the Michael acceptor's π-electron system.

Original languageEnglish
Pages (from-to)8922-8926
Number of pages5
JournalAngewandte Chemie - International Edition
Volume58
Issue number26
DOIs
Publication statusPublished - 24 Jun 2019

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Nucleophiles
Addition reactions
Chemical activation
Density functional theory
Molecules
Electrons

Keywords

  • activation strain model
  • density functional calculations
  • halogen bonding
  • Michael addition
  • Pauli repulsion
  • reactivity

Cite this

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title = "How Dihalogens Catalyze Michael Addition Reactions",
abstract = "We have quantum chemically analyzed the catalytic effect of dihalogen molecules (X2=F2, Cl2, Br2, and I2) on the aza-Michael addition of pyrrolidine and methyl acrylate using relativistic density functional theory and coupled-cluster theory. Our state-of-the-art computations reveal that activation barriers systematically decrease as one goes to heavier dihalogens, from 9.4 kcal mol−1 for F2 to 5.7 kcal mol−1 for I2. Activation strain and bonding analyses identify an unexpected physical factor that controls the computed reactivity trends, namely, Pauli repulsion between the nucleophile and Michael acceptor. Thus, dihalogens do not accelerate Michael additions by the commonly accepted mechanism of an enhanced donor–acceptor [HOMO(nucleophile)–LUMO(Michael acceptor)] interaction, but instead through a diminished Pauli repulsion between the lone-pair of the nucleophile and the Michael acceptor's π-electron system.",
keywords = "activation strain model, density functional calculations, halogen bonding, Michael addition, Pauli repulsion, reactivity",
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How Dihalogens Catalyze Michael Addition Reactions. / Hamlin, Trevor A.; Fernández, Israel; Bickelhaupt, F. Matthias.

In: Angewandte Chemie - International Edition, Vol. 58, No. 26, 24.06.2019, p. 8922-8926.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

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AU - Hamlin, Trevor A.

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AU - Bickelhaupt, F. Matthias

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N2 - We have quantum chemically analyzed the catalytic effect of dihalogen molecules (X2=F2, Cl2, Br2, and I2) on the aza-Michael addition of pyrrolidine and methyl acrylate using relativistic density functional theory and coupled-cluster theory. Our state-of-the-art computations reveal that activation barriers systematically decrease as one goes to heavier dihalogens, from 9.4 kcal mol−1 for F2 to 5.7 kcal mol−1 for I2. Activation strain and bonding analyses identify an unexpected physical factor that controls the computed reactivity trends, namely, Pauli repulsion between the nucleophile and Michael acceptor. Thus, dihalogens do not accelerate Michael additions by the commonly accepted mechanism of an enhanced donor–acceptor [HOMO(nucleophile)–LUMO(Michael acceptor)] interaction, but instead through a diminished Pauli repulsion between the lone-pair of the nucleophile and the Michael acceptor's π-electron system.

AB - We have quantum chemically analyzed the catalytic effect of dihalogen molecules (X2=F2, Cl2, Br2, and I2) on the aza-Michael addition of pyrrolidine and methyl acrylate using relativistic density functional theory and coupled-cluster theory. Our state-of-the-art computations reveal that activation barriers systematically decrease as one goes to heavier dihalogens, from 9.4 kcal mol−1 for F2 to 5.7 kcal mol−1 for I2. Activation strain and bonding analyses identify an unexpected physical factor that controls the computed reactivity trends, namely, Pauli repulsion between the nucleophile and Michael acceptor. Thus, dihalogens do not accelerate Michael additions by the commonly accepted mechanism of an enhanced donor–acceptor [HOMO(nucleophile)–LUMO(Michael acceptor)] interaction, but instead through a diminished Pauli repulsion between the lone-pair of the nucleophile and the Michael acceptor's π-electron system.

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