Related Experiment Video
Updated: Jun 7, 2025

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Iron-catalysed intramolecular C(sp3)-H amination of alkyl azides
Kai Wu1, Chi-Ming Che1,2
1State Key Laboratory of Synthetic Chemistry, Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China. cmche@hku.hk.
Abstract:
Iron-catalysed intramolecular C(sp3)-H amination of alkyl azides (N3R, R = alkyl) via the iron-alkylnitrene/alkylimido (Fe(NR)) intermediate, is an appealing synthetic approach for the synthesis of various N-heterocycles. This approach provides a direct atom-economy strategy for constructing C(sp3)-N bonds, with nitrogen gas as the only by-product and iron is a biocompatible, cheap, and earth-abundant metal. However, C(sp3)-H amination with alkyl azides is challenging because alkyl nitrenes readily undergo 1,2-hydride migration to imines. This article summarizes recent major advances in this field in terms of catalyst design, substrate scope expansion, stereoselectivity control, understanding of key reaction intermediates, and applications in the synthesis of complex natural products and pharmaceuticals.
Related Concept Videos
Preparation of 1° Amines: Azide Synthesis
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Preparation of Amines: Reductive Amination of Aldehydes and Ketones
Preparation of 1° Amines: Gabriel Synthesis
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Acid Halides to Amides: Aminolysis
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism
Amines to Amides: Acylation of Amines
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...

