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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.

Conformations of Cycloalkanes

Conformations of Cycloalkanes

Adolf von Baeyer attempted to explain the instabilities of small and large cycloalkane rings using the concept of angle strain — the strain caused by the deviation of bond angles from the ideal 109.5° tetrahedral value for sp3 hybridized carbons. However, while cyclopropane and cyclobutane are strained, as expected from their highly compressed bond angles, cyclopentane is more strained than predicted, and cyclohexane is virtually strain-free. Hence, Baeyer’s theory that was based on the...

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).

Pericyclic Reactions: Introduction

Pericyclic Reactions: Introduction

Pericyclic reactions are organic reactions that occur via a concerted mechanism without generating any intermediates. The reactions proceed through the movement of electrons in a closed loop to form a cyclic transition state, where rearrangement of the σ and π bonds yields specific products.
Pericyclic reactions can be classified into three categories: electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. Electrocyclic reactions and sigmatropic rearrangements are...

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Constructing Cyclic Peptides Using an On-Tether Sulfonium Center

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Strained cyclophane natural products: macrocyclization at its limits.

Tanja Gulder¹, Phil S Baran

¹RWTH Aachen University, Institute of Organic Chemistry, Landoltweg 1, 52056 Aachen, Germany. tanja.gulder@rwth-aachen.de

Natural Product Reports

|June 26, 2012

Summary

This summary is machine-generated.

Synthesizing small cyclophane natural products is challenging due to macrocyclization difficulties. This review focuses on strategies for creating these rigid, configurationally stable molecules with potential pharmaceutical applications.

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Area of Science:

Organic Chemistry
Natural Product Synthesis
Medicinal Chemistry

Background:

Cyclophane natural products are structurally diverse and possess significant pharmaceutical activities.
Macrocyclization is a critical and challenging step in synthesizing these compounds, especially for smaller cyclophanes.
Restricted rotation of aromatic rings in cyclophanes adds complexity to their synthesis.

Purpose of the Study:

To review the synthetic challenges associated with cyclophane natural products.
To highlight strategies for the macrocyclization step in cyclophane synthesis.
To focus on cyclophanes exhibiting configurational stability.

Main Methods:

Review of existing literature on cyclophane synthesis.
Analysis of different macrocyclization strategies.
Focus on methods applicable to configurationally stable cyclophanes.

Main Results:

Macrocyclization remains the central challenge in assembling rigid cyclophane structures.
Established synthetic reactions often fail for cyclophane ring-closing steps, necessitating novel approaches.
Development of new strategies is crucial for efficient synthesis of these complex molecules.

Conclusions:

The synthesis of cyclophane natural products, particularly those with configurational stability, requires specialized strategies.
Overcoming macrocyclization challenges is key to accessing these biologically relevant compounds.
Continued innovation in synthetic methodology is essential for advancing the field.