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Related Concept Videos

Cycloaddition Reactions: Overview01:16

Cycloaddition Reactions: Overview

Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
Cycloaddition Reactions: MO Requirements for Photochemical Activation01:12

Cycloaddition Reactions: MO Requirements for Photochemical Activation

Some cycloaddition reactions are activated by heat, while others are initiated by light. For example, a [2 + 2] cycloaddition between two ethylene molecules occurs only in the presence of light. It is photochemically allowed but thermally forbidden.
Cycloaddition Reactions: MO Requirements for Thermal Activation01:16

Cycloaddition Reactions: MO Requirements for Thermal Activation

Thermal cycloadditions are reactions where the source of activation energy needed to initiate the reaction is provided in the form of heat. A typical example of a thermally-allowed cycloaddition is the Diels–Alder reaction, which is a [4 + 2] cycloaddition. In contrast, a [2 + 2] cycloaddition is thermally forbidden.
Reduction of Benzene to Cyclohexane: Catalytic Hydrogenation01:28

Reduction of Benzene to Cyclohexane: Catalytic Hydrogenation

Unlike the easy catalytic hydrogenation of an alkene double bond, hydrogenation of a benzene double bond under similar reaction conditions does not take place easily. For example, in the reduction of stilbene, the benzene ring remains unaffected while the alkene bond gets reduced. Hydrogenation of an alkene double bond is exothermic and a favorable process. In contrast, to hydrogenate the first unsaturated bond of benzene, an energy input is needed; that is, the process is endothermic. This is...
Nucleophilic Aromatic Substitution: Elimination–Addition01:11

Nucleophilic Aromatic Substitution: Elimination–Addition

Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is confirmed through isotopic...
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation01:27

Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation

Robinson annulation is a base-catalyzed reaction for the synthesis of 2-cyclohexenone derivatives from 1,3-dicarbonyl donors (such as cyclic diketones, β-ketoesters, or β-diketones) and α,β-unsaturated carbonyl acceptors. Named after Sir Robert Robinson, who discovered it, this reaction yields a six-membered ring with three new C–C bonds (two σ bonds and one π bond).

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Related Experiment Video

Updated: Jun 17, 2026

Preparation of a Corannulene-functionalized Hexahelicene by Copper(I)-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units
09:35

Preparation of a Corannulene-functionalized Hexahelicene by Copper(I)-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

Published on: September 18, 2016

Exploring the Copper(I)-Catalyzed Azide-Alkyne Cycloaddition: A Unified Reaction Valley Approach and Local

Lily McKenna1, Thomas More Sexton2, Marek Freindorf3

  • 1Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138, United States.

The Journal of Physical Chemistry. A
|June 16, 2026
PubMed
Summary

The dinuclear copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) mechanism offers the most efficient pathway, with the lowest activation energy for 1,4-addition. This study reveals key mechanistic insights for designing improved CuAAC catalysts.

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Last Updated: Jun 17, 2026

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[(DPEPhos)(bcp)Cu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst
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[(DPEPhos)(bcp)Cu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst

Published on: May 21, 2019

Area of Science:

  • Computational Chemistry
  • Catalysis
  • Organic Synthesis

Background:

  • Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is a versatile click reaction known for its adaptability, regioselectivity, and high yield.
  • Understanding the detailed reaction mechanism is crucial for optimizing catalyst design and reaction efficiency.

Purpose of the Study:

  • To investigate the reaction mechanism of CuAAC using advanced theoretical methods.
  • To compare the catalytic efficiency of mononuclear and dinuclear copper catalysts.
  • To identify the most effective catalytic pathway for 1,4-product formation.

Main Methods:

  • Employed the Unified Reaction Valley Approach (URVA) and Local Mode Analysis (LMA).
  • Utilized B3LYP/cc-pVTZ and CCDT(T) levels of theory for calculations.
  • Explored both mononuclear and dinuclear Cu(I)-acetylide catalyst mechanisms.

Main Results:

  • The dinuclear mechanism for 1,4-addition exhibited the lowest activation energy, indicating it as the most effective catalytic pathway.
  • The initial cycloaddition step possesses the highest energy barrier, which is minimized in the dinuclear catalyst.
  • URVA analysis revealed that the transition state precedes C-N bond formation, with energy barriers arising from electronic structural changes.

Conclusions:

  • The dinuclear catalytic pathway is superior for CuAAC, particularly for 1,4-product formation.
  • Regioselectivity may be influenced by catalyst dissociation and product stabilization, as suggested by LMA.
  • These mechanistic findings provide a foundation for developing more efficient CuAAC catalysts.