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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.

[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.

Electrophilic 1,2- and 1,4-Addition of X2 to 1,3-Butadiene

Electrophilic 1,2- and 1,4-Addition of X₂ to 1,3-Butadiene

Electrophilic addition of halogens to alkenes proceeds via a cyclic halonium ion to form a 1,2-dihalide or a vicinal dihalide.

Electrophilic 1,2- and 1,4-Addition of HX to 1,3-Butadiene

Electrophilic 1,2- and 1,4-Addition of HX to 1,3-Butadiene

The electrophilic addition of hydrogen halides such as HBr to alkenes and nonconjugated dienes gives a single product as per Markovnikov’s rule.

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.

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.

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A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

Published on: January 21, 2020

Nitrone Cycloadditions of 1,2-Cyclohexadiene.

Joyann S Barber¹, Evan D Styduhar¹, Hung V Pham¹

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

Journal of the American Chemical Society

|February 9, 2016

Summary

This study introduces the first 1,3-dipolar cycloadditions using 1,2-cyclohexadiene, a strained allene. The reaction with nitrones yields isoxazolidines with high selectivity, demonstrating a novel synthetic route.

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Published on: May 26, 2019

Area of Science:

Organic Chemistry
Synthetic Chemistry

Background:

1,2-Cyclohexadiene is a strained allene with limited synthetic applications.
1,3-Dipolar cycloadditions are versatile reactions for forming heterocyclic compounds.

Purpose of the Study:

To explore the reactivity of 1,2-cyclohexadiene in 1,3-dipolar cycloadditions.
To develop a novel synthetic methodology utilizing this strained allene.

Main Methods:

In situ generation of 1,2-cyclohexadiene under mild conditions.
Trapping of the reactive intermediate with various nitrones.
Density Functional Theory (DFT) calculations to elucidate reaction mechanisms and selectivities.

Main Results:

Successful 1,3-dipolar cycloaddition of 1,2-cyclohexadiene with nitrones.
Formation of isoxazolidine products in synthetically useful yields.
High regioselectivity and endo preference observed, leading to controlled stereochemistry.
Demonstrated utility for synthesizing compounds with multiple heterocyclic units.

Conclusions:

1,2-Cyclohexadiene can be effectively utilized in cycloaddition reactions.
This methodology provides a new strategy for constructing complex heterocyclic molecules.
Exploitation of strained intermediates offers novel synthetic pathways.