Stereoselective Synthesis of Nitrogen-Containing Compounds from Enamines

Masaharu Sugiura1, Takeru Kashiwagi1, Mai Ito1

  • 1Graduate School of Pharmaceutical Sciences and ‡Priority Organization for Innovation and Excellence, Kumamoto University , 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.

Related Concept Videos

Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction01:26

Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction

α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.
4.2K
Aldehydes and Ketones with Amines: Imine and Enamine Formation Overview01:16

Aldehydes and Ketones with Amines: Imine and Enamine Formation Overview

Primary amines react with carbonyl compounds—aldehydes and ketones—to generate imines. Imines consist of a C=N double bond and are named Schiff bases after its discoverer—the German chemist Hugo Schiff. On the other hand, secondary amines react with carbonyl compounds to give enamines. In enamines, the presence of a C=C double bond adjacent to the nitrogen atom leads to the delocalization of the lone pair.
6.9K
Types of Enols and Enolates01:19

Types of Enols and Enolates

Aldehydes and ketones form enols, although only about 1% of the enol is present at the equilibrium for simple monocarbonyl compounds. The enol form is undetectable for acetaldehyde, present as only 1.5 × 10−4 % of acetone, and present as only 1.2% of cyclohexanone. Two kinds of regioisomeric enols are possible for unsymmetrical ketones, and their net composition is 1% at equilibrium. This instability is due to the lower bond energy of C=C than the C=O group. The additional...
3.7K
Aldehydes and Ketones with Amines: Enamine Formation Mechanism01:14

Aldehydes and Ketones with Amines: Enamine Formation Mechanism

Enamine formation involves the addition of carbonyl compounds to a secondary amine through a series of reactions. The mechanism begins with the generation of carbinolamine, a nucleophilic attack followed by several proton transfer reactions. The hydroxyl group of the carbinolamine is converted into water to make a better leaving group that can push the reaction forward by eliminating a water molecule. In enamine formation, the last step involves the abstraction of a proton from the α carbon to...
8.0K
Preparation of 1° Amines: Gabriel Synthesis01:28

Preparation of 1° Amines: Gabriel Synthesis

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...
4.8K
Preparation of 1° Amines: Azide Synthesis01:22

Preparation of 1° Amines: Azide Synthesis

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...
4.7K