Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Cycloaddition Reactions: MO Requirements for Thermal Activation

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.

Cycloaddition Reactions: Overview

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 Activation

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.

[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction

[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction

The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.

Woodward–Hoffmann Selection Rules and Microscopic Reversibility

Woodward–Hoffmann Selection Rules and Microscopic Reversibility

Electrocyclic reactions, cycloadditions, and sigmatropic rearrangements are concerted pericyclic reactions that proceed via a cyclic transition state. These reactions are stereospecific and regioselective. The stereochemistry of the products depends on the symmetry characteristics of the interacting orbitals and the reaction conditions. Accordingly, pericyclic reactions are classified as either symmetry-allowed or symmetry-forbidden. Woodward and Hoffmann presented the selection criteria for...

Thermal Electrocyclic Reactions: Stereochemistry

Thermal Electrocyclic Reactions: Stereochemistry

The stereochemistry of electrocyclic reactions is strongly influenced by the orbital symmetry of the polyene HOMO. Under thermal conditions, the reaction proceeds via the ground-state HOMO.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Determining Quantum Mechanical Methods Suitable for Quantitative Modeling of Hydrogen Atom Transfer by Halogen Atoms.

Journal of chemical theory and computation·2026

Same author

Photo-Triggered, Fast, and Fluorogenic Thiophene-Based Cycloalkynes for the Bioorthogonal Fluorescent Labeling of 1,3-Dipole-Tagged Molecules in No-Wash Conditions.

Angewandte Chemie (International ed. in English)·2026

Same author

Cobaloxime-catalysed regiodivergent hydrogen atom transfer for alkenyl and allylic carbamoylation with branched alkenes.

Nature communications·2026

Same author

Non-Enzymatic Formation of Chaxines and Natural Steroidal Derivatives via Ergosterol Air Oxidation.

The Journal of organic chemistry·2026

Same author

Computational Insight into Free Molecular Rotors in Crystalline Solids: Inertial Rotation and Langevin Dynamics.

Journal of the American Chemical Society·2026

Same author

Rule-breaking in chemical synthesis.

Science advances·2026

Same journal

Ir-Catalyzed Formal 1,2-Fluorine Migration in Fluorocarbenes.

Organic letters·2026

Same journal

Leveraging Bayesian Optimization for Accelerated Ligand Selection in Atroposelective Negishi Coupling.

Organic letters·2026

Same journal

Synthesis of Azido Energetic Compounds Based on 2-(Pyrazol-4-yl)pyrazolo[4,3-<i>e</i>][1,2,4]triazolo[1,5-<i>c</i>][1,2,3]triazine via an Atom-Economical Intramolecular Dutt-Wormall-Type Process.

Organic letters·2026

Same journal

Modular Synthesis of Dinitramino-Functionalized Pyrazole-Tetrazole and Its Derivatives: Achieving Superior Detonation Performance.

Organic letters·2026

Same journal

Light-Driven Iron-Catalyzed Decarboxylative Fluorosulfonylation of Aliphatic Carboxylic Acids.

Organic letters·2026

Same journal

Chiral Phosphoric Acid-Catalyzed Enantioselective Dearomative Spirocyclization of Phenol-Ynamides by Kinetic Resolution.

Organic letters·2026

See all related articles

Search research articles

Related Experiment Video

Updated: Jul 19, 2025

Novel Techniques for Observing Structural Dynamics of Photoresponsive Liquid Crystals

Novel Techniques for Observing Structural Dynamics of Photoresponsive Liquid Crystals

Published on: May 29, 2018

Orthogonal Inverse-Electron-Demand Cycloaddition Reactions Controlled by Frontier Molecular Orbital Interactions.

Dennis Svatunek^1,2, Konrad Chojnacki³, Titas Deb³

¹Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095, United States.

Organic Letters

|August 17, 2023

Summary

This summary is machine-generated.

Researchers developed new bioorthogonal click chemistry for simultaneous biomolecule labeling. This method uses distinct reactant pairs, enabling precise labeling of multiple targets like proteins with different fluorescent tags.

More Related Videos

Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging

Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging

Published on: February 3, 2015

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions

Published on: March 20, 2014

Related Experiment Videos

Last Updated: Jul 19, 2025

Novel Techniques for Observing Structural Dynamics of Photoresponsive Liquid Crystals

Novel Techniques for Observing Structural Dynamics of Photoresponsive Liquid Crystals

Published on: May 29, 2018

Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging

Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging

Published on: February 3, 2015

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions

Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions

Published on: March 20, 2014

Area of Science:

Chemical Biology
Organic Chemistry
Bioconjugation

Background:

Bioorthogonal chemistry allows reactions within biological systems without interference.
Simultaneous labeling of multiple biomolecules requires orthogonal reaction pairs.
Existing methods may lack sufficient orthogonality or broad applicability.

Purpose of the Study:

To develop novel chemoselective bioorthogonal reactant pairs for simultaneous labeling.
To exploit frontier molecular orbital interactions for reaction control.
To demonstrate orthogonal labeling of multiple proteins.

Main Methods:

Investigated reactivity differences between cyclic dienes, strained alkynes, and isonitriles.
Utilized transition state frontier molecular orbital interaction energies to predict selectivity.
Performed simultaneous labeling of two distinct proteins with different fluorophores.

Main Results:

Established that five-membered cyclic dienes react with strained alkynes but not isonitriles.
Demonstrated that bulky-substituted tetrazines react with isonitriles, not strained alkynes.
Successfully achieved orthogonal labeling of two proteins using these distinct reaction pairs.

Conclusions:

A new strategy for accessing orthogonal click reactions based on orbital interactions was established.
This approach enables the simultaneous labeling of multiple biomolecules with high selectivity.
The developed method offers a versatile tool for advanced bioconjugation applications.