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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.
[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement01:21

[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement

The Cope rearrangement is classified as a [3,3] sigmatropic shift in 1,5-dienes, leading to a more stable, isomeric 1,5-diene. The reaction involves a concerted movement of six electrons, four from two π bonds and two from a σ bond, via an energetically favorable chair-like transition state.
Thermal and Photochemical Electrocyclic Reactions: Overview01:26

Thermal and Photochemical Electrocyclic Reactions: Overview

Electrocyclic reactions are reversible reactions. They involve an intramolecular cyclization or ring-opening of a conjugated polyene. Shown below are two examples of electrocyclic reactions. In the first reaction, the formation of the cyclic product is favored. In contrast, in the second reaction, ring-opening is favored due to the high ring strain associated with cyclobutene formation.
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.
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction01:16

[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.
Aromatic Hydrocarbon Cations: Structural Overview01:18

Aromatic Hydrocarbon Cations: Structural Overview

Cycloheptatriene is a neutral monocyclic unsaturated hydrocarbon that consists of an odd number of carbon atoms and an intervening sp3 carbon in the ring. The three double bonds in the ring correspond to 6 π electrons, which is a Huckel number, and therefore satisfies the criteria of 4n + 2 π electrons. However, the intervening sp3 carbon disrupts the continuous overlap of p orbitals. As a result, cycloheptatriene is not aromatic.
Removing one hydrogen from the intervening CH2 group with both...

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Related Experiment Video

Updated: Jun 4, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
10:17

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones

Published on: February 7, 2019

Pyridine C─N Transposition via Cycloaddition-Cycloreversion.

Aífe Conboy1, Michael F Greaney1

  • 1Department of Chemistry, University of Manchester, Manchester, UK.

Angewandte Chemie (International Ed. in English)
|June 3, 2026
PubMed
Summary
This summary is machine-generated.

This study introduces a novel skeletal-editing method for pyridine synthesis. It enables the transposition of nitrogen atoms, creating difficult-to-access 3-alkylated pyridines via a cycloaddition/cycloreversion strategy.

Keywords:
ANRORCcycloaddition–cycloreversionpyridineskeletal‐editingtransposition

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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
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Solid-phase Synthesis of [4.4] Spirocyclic Oximes

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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Published on: August 22, 2018

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Last Updated: Jun 4, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
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Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones

Published on: February 7, 2019

Solid-phase Synthesis of [4.4] Spirocyclic Oximes
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Solid-phase Synthesis of [4.4] Spirocyclic Oximes

Published on: February 6, 2019

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
11:45

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Published on: August 22, 2018

Area of Science:

  • Organic Chemistry
  • Synthetic Chemistry
  • Medicinal Chemistry

Background:

  • Selective nitrogen atom incorporation is crucial for designing functional molecules and drugs.
  • Accessing meta-functionalized pyridines, such as 3-alkylated pyridines, remains a synthetic challenge.
  • Current synthetic methods often struggle with the regioselective functionalization of pyridine rings.

Purpose of the Study:

  • To develop a novel skeletal-editing strategy for pyridine nitrogen atom transposition.
  • To establish an efficient route to synthetically challenging 3-alkylated pyridines.
  • To demonstrate the utility of the introduced sulfone functionality for further pyridine derivatization.

Main Methods:

  • A cycloaddition/cycloreversion (CACR) strategy was employed to transpose pyridine nitrogen atoms.
  • The method facilitates the conversion of readily available 4-aryl and alkyl pyridines into meta-functionalized isomers.
  • Sulfone functionality was introduced during the cycloaddition step, enabling subsequent C-X and C-C bond formations.

Main Results:

  • A new synthetic route to 3-alkylated pyridines was successfully established.
  • The CACR strategy effectively transposed pyridine nitrogen atoms, overcoming existing synthetic limitations.
  • The introduced sulfone group proved versatile for subsequent cross-coupling and functionalization reactions, expanding pyridine synthesis possibilities.

Conclusions:

  • The developed skeletal-editing approach offers a powerful new method for accessing valuable 3-alkylated pyridines.
  • This strategy provides a versatile platform for pyridine synthesis and functionalization, with implications for drug discovery.
  • The cycloaddition/cycloreversion strategy represents a significant advancement in heterocyclic chemistry.