Related Experiment Video
Updated: Mar 28, 2026
11:04
Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
3.6K
Iron-Catalyzed Site-Selective γ-C(sp3)-H Azidation of Hydroxylamine Derivatives
Hugo Esteves1, Tania Xavier1, Guillaume Prestat1
1Université Paris Cité, CNRS, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, Paris F-75006, France.
The Journal of Organic Chemistry
|March 27, 2026
Summary
This study introduces an iron-catalyzed method for C(sp3)-H azidation. The reaction achieves selective functionalization at the gamma position relative to carbonyl groups using a novel hydrogen atom transfer process.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- C-H functionalization is a key area in synthetic chemistry.
- Developing selective methods for introducing nitrogen-containing groups is important.
- Iron catalysis offers a sustainable alternative to precious metal catalysts.
Purpose of the Study:
- To develop an iron-catalyzed intermolecular C(sp3)-H azidation reaction.
- To achieve exclusive gamma-selectivity relative to a carbonyl group.
- To provide an efficient route to azido-amides and azido-carbamates.
Main Methods:
- Utilizing hydroxylamine derivatives and trimethylsilyl azide.
- Employing a simple iron catalyst.
- Leveraging a 1,5-hydrogen atom transfer mechanism initiated by an iron-nitrenoid species.
Main Results:
- Exclusive gamma-selectivity was achieved in the C(sp3)-H azidation.
- The reaction proceeds efficiently with a broad substrate scope.
- Azido-amide and azido-carbamate products were synthesized effectively.
Conclusions:
- The developed iron-catalyzed strategy enables selective C-H azidation.
- This method offers a practical approach for synthesizing valuable nitrogen-containing compounds.
- The 1,5-hydrogen atom transfer mechanism is key to the observed selectivity.
More Related Videos
Related Concept Videos
01:22Preparation of 1° Amines: Azide Synthesis
4.8K
Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
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...
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...
4.8K
01:28Preparation of 1° Amines: Gabriel Synthesis
5.0K
Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
5.0K
01:19Diazonium Group Substitution: –OH and –H
3.5K
Nitrous acid, a weak acid, is prepared in situ via the reaction of sodium nitrite with a strong acid under cold conditions. This nitrous acid prepared in situ reacts with primary arylamines to form arenediazonium salts. Such reactions are known as diazotization reactions. As shown in Figure 1, the formation of arenediazonium salts begins with the decomposition of nitrous acid in an acidic solution to give nitrosonium ions.
3.5K
01:29Preparation of Amines: Reduction of Oximes and Nitro Compounds
4.9K
Oximes can be reduced to primary amines using catalytic hydrogenation, hydride reduction, or sodium metal reduction. The reduction of aliphatic and aromatic nitro compounds to primary amines takes place by either catalytic hydrogenation or by using active metals like Fe, Zn, and Sn in the presence of an acid.
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...
4.9K
01:38Preparation of Amines: Reductive Amination of Aldehydes and Ketones
4.2K
Carbonyl compounds and primary amines undergo reductive amination first to produce imines, followed by secondary amines in the same reaction mixture, using selective reducing agents like sodium cyanoborohydride or sodium triacetoxyborohydride. Reductive amination produces different degrees of substitution of amines depending on the starting amine substrate.
4.2K
01:23Aldehydes and Ketones with Amines: Imine Formation Mechanism
9.5K
Imine formation involves the addition of carbonyl compounds to a primary amine. It begins with the generation of carbinolamine through a series of steps involving an initial nucleophilic attack and then several proton transfer reactions. The second part includes the elimination of water, as a leaving group, to give the imine.
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
9.5K