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[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: 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.

Structure of Conjugated Dienes

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...

Structural Isomerism

Structural Isomerism

Isomerism in Complexes
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly, SCN− can...

Structures of Carboxylic Acid Derivatives

Structures of Carboxylic Acid Derivatives

Structure of Carboxylic Acid Derivatives
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the unhybridized p...

Diels–Alder Reaction Forming Cyclic Products: Stereochemistry

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.

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Updated: Mar 16, 2026

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

A Multidimensional Diversity-Oriented Synthesis Strategy for Structurally Diverse and Complex Macrocycles.

Feilin Nie¹, Dominique L Kunciw¹, David Wilcke¹

¹Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.

Angewandte Chemie (International Ed. in English)

|August 4, 2016

Summary

This summary is machine-generated.

Researchers developed a new multidimensional synthesis strategy for creating diverse macrocycles, overcoming limitations in drug discovery. This approach efficiently generates novel, highly-functionalized macrocyclic libraries with broad structural variety.

Keywords:

diversity-oriented synthesis macrocycles molecular diversity synthesis design synthetic methods

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Last Updated: Mar 16, 2026

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

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Published on: February 7, 2019

Synthesis of a Water-soluble Metal–Organic Complex Array

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Published on: October 8, 2016

Solid-phase Synthesis of [4.4] Spirocyclic Oximes

Solid-phase Synthesis of [4.4] Spirocyclic Oximes

Published on: February 6, 2019

Area of Science:

Medicinal Chemistry
Organic Synthesis
Computational Chemistry

Background:

Synthetic macrocycles are valuable in drug discovery but library generation is challenging.
Existing methods lack versatility for creating structurally diverse macrocycle libraries.

Purpose of the Study:

To introduce a novel multidimensional diversity-oriented synthesis (MDOS) strategy for macrocycles.
To generate a library of structurally diverse and highly-functionalized macrocycles.
To analyze the impact of synthesis on molecular shape diversity.

Main Methods:

Exploited the reactivity of aza-ylides and imines.
Employed eight distinct macrocyclization methods, including two novel techniques.
Utilized computational analyses to assess molecular shape space coverage.

Main Results:

Successfully synthesized a library of 45 novel macrocycles.
Achieved significant structural diversity across various scaffolds and motifs.
Demonstrated broad coverage of molecular shape space.

Conclusions:

The MDOS strategy provides a versatile platform for macrocycle library synthesis.
This approach enhances the potential of macrocycles in drug discovery by enabling access to diverse chemical space.
Computational insights guide the design of future macrocycle synthesis for targeted shape properties.