Switchable synthesis of 3-aminoindolines and 2'-aminoarylacetic acids using Grignard reagents and 3-azido-2-hydroxyindolines
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Researchers developed a switchable synthesis for 3-aminoindolines and 2'-aminoaryl acetic acids. Reaction conditions control chemoselectivity, enabling dual product formation from the same starting material.
Area Of Science
- Organic Chemistry
- Synthetic Chemistry
Background
- Developing efficient synthetic routes for nitrogen-containing heterocycles is crucial in organic chemistry.
- Controlling chemoselectivity in reactions involving azido compounds presents a significant synthetic challenge.
Purpose Of The Study
- To establish a switchable synthetic strategy for producing 3-aminoindolines and 2 -aminoaryl acetic acids.
- To investigate the influence of reaction conditions on the chemoselective outcome of denitrogenative electrophilic amination.
Main Methods
- Utilized Grignard reagents for denitrogenative electrophilic amination of 3-azido-2-hydroxyindolines.
- Systematically varied reaction conditions, including solvents and temperature, to control chemoselectivity.
- Employed isotope-labeling experiments to elucidate reaction mechanisms.
Main Results
- Successfully achieved switchable synthesis of both 3-aminoindolines and 2 -aminoaryl acetic acids from a single precursor.
- Demonstrated that reaction conditions (solvent, temperature) dictate the chemoselective pathway.
- Identified an aziridine intermediate in the formation of 2 -aminoaryl acetic acids through isotopic labeling.
Conclusions
- The developed method offers a versatile approach to synthesizing distinct nitrogen-containing compounds.
- Reaction condition optimization is key to controlling chemoselectivity in this transformation.
- The findings provide mechanistic insights into the formation of 2 -aminoaryl acetic acids.
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
Related Concept Videos
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...
Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
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...
Organomagnesium halides, commonly known as Grignard reagents, convert acid halides to tertiary alcohols. The reaction requires two equivalents of the Grignard reagent and proceeds via a ketone intermediate.
Grignard reagents are a source of carbanions and function as nucleophiles. The mechanism begins with the nucleophilic attack by the carbanion at the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs,...
In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.
In the Curtius rearrangement, acyl azides are converted into primary amines under thermal conditions, accompanied by the loss of gaseous N2 and CO2. The loss of nitrogen acts as...
The Hofmann and Curtius rearrangement reactions can be applied to synthesize primary amines from carboxylic acid derivatives such as amides and acyl azides. In the Hofmann rearrangement, a primary amide undergoes deprotonation in the presence of a base, followed by halogenation to generate an N-haloamide. A second proton abstraction produces a stabilized anionic species, which rearranges to an isocyanate intermediate via an alkyl group migration from the carbonyl carbon to the neighboring...