Related Experiment Video
Updated: Apr 27, 2026
11:45
Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
7.9K
Azabicycles construction: the transannular ring contraction with N-protected nucleophiles
Antonio Rizzo1, Syuzanna R Harutyunyan
1University of Groningen, Stratingh Institute, Nijenborgh 4, 9747 AG, Groningen, Netherlands. s.r.harutyunyan@rug.nl.
Organic & Biomolecular Chemistry
|July 10, 2014
Summary
This review details a synthetic strategy using tandem transannular ring contractions and protecting group cleavages for creating azabicyclic scaffolds. This efficient method is key for synthesizing bioactive alkaloids and complex molecules.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Medicinal Chemistry
Background:
- Synthetic strategies are vital for the success, economy, and efficiency of chemical synthesis.
- Azabicyclic scaffolds are important structural motifs found in numerous bioactive alkaloids.
Purpose of the Study:
- To review the applications of tandem transannular ring contractions-protecting group cleavages for synthesizing azabicyclic scaffolds.
- To highlight the efficiency and broad applicability of this synthetic strategy.
Main Methods:
- Utilizing medium-sized cyclic N-protected amines with an activatable electrophilic site.
- Inducing transannular reactions via protecting group fragmentation and subsequent ring contraction.
Main Results:
- Demonstrated a versatile strategy for constructing azabicyclic scaffolds.
- Showcased the application of this method in assembling small molecules to complex molecular architectures.
Conclusions:
- Tandem transannular ring contractions-protecting group cleavages offer an efficient synthetic route to azabicyclic compounds.
- This strategy is applicable across a range of molecular complexities, from simple to intricate structures.
Related Concept Videos
01:11Nucleophilic Aromatic Substitution: Elimination–Addition
2.8K
Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is...
2.8K
01:30Nucleophilic Aromatic Substitution: Addition–Elimination (SNAr)
3.0K
Nucleophilic substitution in aromatic compounds is feasible in substrates bearing strong electron-withdrawing substituents positioned ortho or para to the leaving group. The reaction proceeds via two steps: the addition of the nucleophile and the elimination of the leaving group.
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between...
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between...
3.0K
01:10Nomenclature of Aryl and Heterocyclic Amines
2.2K
The simplest aromatic amine is phenylamine, which contains an –NH2 functionality directly attached to an aromatic ring. The name aniline is designated for this skeleton. As shown in Figure 1, the common names of the functionalized anilines involve prefixes ortho-, meta-, and para- to indicate the substitution position. Different functionalized aniline derivatives also have notable trivial names.
2.2K
01:11ortho–para-Directing Activators: –CH3, –OH, –NH2, –OCH3
5.0K
All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
5.0K
01:16Cycloaddition Reactions: Overview
2.3K
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.
2.3K
01:27Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
2.2K
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).
2.2K