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Related Concept Videos

[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.
Benzene to 1,4-Cyclohexadiene: Birch Reduction Mechanism01:18

Benzene to 1,4-Cyclohexadiene: Birch Reduction Mechanism

Birch reduction uses solvated electrons as reducing agents. The reaction converts benzene to 1,4-cyclohexadiene. The reaction proceeds by the transfer of a single electron to the ring to form a benzene radical anion. This anion is highly basic—it abstracts a proton from the alcohol to form a cyclohexadienyl radical. Another single electron transfer gives the cyclohexadienyl anion. A proton transfer from the alcohol forms 1,4-cyclohexadiene. Since this reduction occurs via radical anion...
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry01:28

Diels–Alder Reaction Forming Cyclic Products: Stereochemistry

The Diels–Alder reaction is one of the robust methods for synthesizing unsaturated six-membered rings. The reaction involves a concerted cyclic movement of six π electrons: four π electrons from the diene and two π electrons from the dienophile.
Preparation of Alkynes: Dehydrohalogenation02:34

Preparation of Alkynes: Dehydrohalogenation

Introduction
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
Disubstituted Cyclohexanes: cis-trans Isomerism02:37

Disubstituted Cyclohexanes: cis-trans Isomerism

Depending upon the different spatial orientation of the substituents, the disubstituted cycloalkanes exhibit two types of stereoisomers. The cis isomers have the substituents on the same side of the ring, whereas the trans isomers have the substituents on the opposite sides. These stereoisomers exhibit different physical properties and cannot be interconverted without breaking the carbon-carbon bonds.
In cyclohexane, the substituents can occupy different positions generating distinct isomers.
Structure of Conjugated Dienes01:16

Structure of Conjugated Dienes

Introduction
Conjugated dienes are compounds characterized by the presence of alternating double and single bonds. In a conjugated system like 1,3-butadiene, the unhybridized 2p orbital on each carbon overlaps continuously, allowing the π electrons to be delocalized across the entire molecule. In contrast, this type of overlap does not occur in cumulated and isolated dienes, such as 2,3-pentadiene and 1,4-pentadiene, respectively. Instead, the π electrons remain localized between the double...

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Related Experiment Video

Updated: Jun 27, 2026

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

Exploring synthetic routes to 6-functionalized 4-azaspiro[2.3]hexanes.

Wei Huang1, Kangqiao Wen1, Scott T Laughlin1

  • 1Department of Chemistry, Stony Brook University, USA. scott.laughlin@stonybrook.edu.

Organic & Biomolecular Chemistry
|June 26, 2026
PubMed
Summary

This study introduces a new method for synthesizing 6-functionalized 4-azaspiro[2.3]hexanes, important for medicinal chemistry. The optimized synthesis uses readily available azetidines and avoids hazardous catalysts, yielding valuable piperidine bioisostere analogues.

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

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Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
04:38

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions

Published on: July 28, 2022

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Last Updated: Jun 27, 2026

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

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

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Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
04:38

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions

Published on: July 28, 2022

Area of Science:

  • Medicinal Chemistry
  • Organic Synthesis
  • Chemical Biology

Background:

  • Azaspirohexanes are valuable scaffolds for creating piperidine bioisosteres.
  • Previous research concentrated on 5-azaspiro[2.3]hexane analogues.
  • The synthesis of 6-functionalized 4-azaspiro[2.3]hexanes was largely unexplored.

Purpose of the Study:

  • To develop a synthetic route for 6-functionalized 4-azaspiro[2.3]hexane analogues.
  • To explore the utility of substituted azetidines as key intermediates.
  • To establish efficient and safe synthetic methodologies.

Main Methods:

  • Utilized substituted azetidines (fluoro-, dimethoxy-, methoxybenzyl-) as intermediates.
  • Optimized intramolecular ring closure of an acyclic amine for azetidine synthesis.
  • Employed azetidine enamine intermediates for spirocycle formation.

Main Results:

  • Achieved efficient synthesis of 3,3-dimethoxy-2-ester azetidine via intramolecular ring closure.
  • Successfully synthesized two 6-functionalized 4-azaspiro[2.3]hexanes: 6-OBn-4-azaspiro[2.3]hexane and 6-dimethoxy-4-azaspiro[2.3]hexane.
  • The developed method avoids hazardous materials and precious-metal catalysts.

Conclusions:

  • Established a viable synthetic pathway for 6-functionalized 4-azaspiro[2.3]hexanes.
  • The synthesized compounds represent novel motifs for medicinal chemistry and chemical biology.
  • The method offers a safe and efficient alternative for accessing these important scaffolds.