Oxidative amination by nitrogen atom insertion into carbon-carbon double bonds
Yannick Brägger1, Ann-Sophie K Paschke1, Nima Nasiri1
1Laboratorium für Organische Chemie, ETH Zürich, Zürich, Switzerland.
Science (New York, N.Y.)
|March 6, 2025
Summary
Researchers developed a new method for synthesizing nitrogen-containing compounds by directly inserting nitrogen into carbon-carbon double bonds. This versatile reaction creates nitriles, amidines, and valuable N-heterocycles using a hypervalent iodine reagent.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- Carbon-nitrogen (C-N) bond formation is essential for synthesizing pharmaceuticals, agrochemicals, and advanced materials.
- Developing efficient methods for C-N bond formation is a key challenge in organic synthesis.
Purpose of the Study:
- To report a novel method for direct nitrogen atom insertion into unactivated carbon-carbon double bonds.
- To demonstrate the conversion of resulting aza-allenium intermediates into nitriles or amidines.
Main Methods:
- Direct insertion of a nitrogen atom into unactivated alkenes.
- Utilizing phenyliodine(III) bis(trifluoroacetate) (PIFA) as a hypervalent iodine reagent.
- Employing chemical trapping experiments for mechanistic studies.
Main Results:
- Successful synthesis of nitriles and amidines from a wide range of unactivated alkenes.
- Demonstrated operational simplicity and high functional group compatibility.
- Access to valuable N-heterocycles and potential for synthesizing amides, amines, and 15N-labeled molecules.
Conclusions:
- The developed method offers a straightforward and versatile approach for C-N bond formation.
- This strategy expands the synthetic toolkit for nitrogen-containing molecules, including pharmaceuticals and materials.
- The reaction's utility is further highlighted by its application in synthesizing N-heterocycles and labeled compounds.
More Related Videos
Related Concept Videos
01:38Preparation of Amines: Reductive Amination of Aldehydes and Ketones
2.7K
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.
2.7K
01:29Preparation of Amines: Reduction of Oximes and Nitro Compounds
3.3K
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,...
3.3K
01:15Phase I Reactions: Oxidation of Carbon-Heteroatom and Miscellaneous Systems
55
Oxidative reactions are pivotal in metabolizing numerous compounds, including pharmaceutical drugs. These reactions often occur in carbon-heteroatom systems, such as carbon-nitrogen, carbon-sulfur, and carbon-oxygen.
In carbon-nitrogen systems, aliphatic and aromatic amines can undergo oxidative reactions. Secondary and tertiary amines, like those found in tricyclic antidepressants, can undergo N-dealkylation, a process that involves the oxidation of the alkyl group. In addition, oxidative...
In carbon-nitrogen systems, aliphatic and aromatic amines can undergo oxidative reactions. Secondary and tertiary amines, like those found in tricyclic antidepressants, can undergo N-dealkylation, a process that involves the oxidation of the alkyl group. In addition, oxidative...
55
01:202° Amines to N-Nitrosamines: Reaction with NaNO2
4.0K
Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
4.0K
01:20Electrophilic Aromatic Substitution: Nitration of Benzene
5.5K
The nitration of benzene is an example of an electrophilic aromatic substitution reaction. It involves the formation of a very powerful electrophile, the nitronium ion, which is linear in shape. The reaction occurs through the interaction of two strong acids, sulfuric and nitric acid.
5.5K
01:20Radical Autoxidation
2.1K
The oxidation of an organic compound in the presence of air or oxygen is called autoxidation. For example, cumene reacts with oxygen to form hydroperoxide. Autoxidation involves initiation, propagation, and termination steps. Many organic compounds are susceptible to autoxidation—especially ethers in the presence of oxygen, which form hydroperoxides. Even though this reaction is slow, old ether bottles contain small amounts of peroxide, which leads to laboratory explosions during ether...
2.1K