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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 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.

[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.

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.

Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry

Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry

Diels–Alder reactions between cyclic dienes locked in an s-cis configuration and dienophiles yield bridged bicyclic products.

Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation

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: May 30, 2025

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

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

Published on: February 7, 2019

Skeletal Editing through Cycloaddition and Subsequent Cycloreversion Reactions.

Pengwei Xu¹, Armido Studer¹

¹Organisch-Chemisches Institut, Universität Münster, Corrensstrasse 40, 48149 Münster, Germany.

Accounts of Chemical Research

|January 28, 2025

Summary

This summary is machine-generated.

Skeletal editing enables precise molecular framework modifications by adding, deleting, or substituting atoms. A novel cycloaddition/cycloreversion strategy allows double-atomic scale manipulation, transforming arenes and heteroarenes for drug discovery.

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

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Area of Science:

Synthetic organic chemistry
Medicinal chemistry
Materials science

Background:

Skeletal editing precisely modifies molecular frameworks, crucial for drug and materials development.
Current methods often focus on single-atom changes, limiting complex structural alterations.
Late-stage skeletal editing accelerates discovery by avoiding costly de novo synthesis.

Purpose of the Study:

To explore skeletal editing via cycloaddition/cycloreversion for double-atomic scale molecular manipulation.
To highlight recent advancements in activating relatively inert substrates for skeletal editing.
To showcase the transformation of pyridines into benzenes and naphthalenes.

Main Methods:

Utilizing cycloaddition followed by cycloreversion to manipulate molecular frameworks.
Developing dearomative processes to activate pyridines into oxazinopyridines.
Reviewing contributions involving heterocycles like tetrazines and triazines.

Main Results:

Demonstrated double-atom transmutation, formal single-atom transmutation, and atom insertion.
Achieved high-yielding transformation of pyridines into benzenes and naphthalenes.
Showcased interconversion of arenes and heteroarenes for late-stage applications.

Conclusions:

Skeletal editing via cycloaddition/cycloreversion offers a powerful route for molecular framework modification.
This strategy facilitates the synthesis of complex molecules and accelerates drug discovery.
Future work should focus on substrate activation for atom incorporation and ring size modification.