Fluorocyanation of enamines
Alexander D Dilman1, Pavel A Belyakov, Marina I Struchkova
1N. D. Zelinsky Institute of Organic Chemistry, 119991 Moscow, Leninsky prosp. 47, Russian Federation. adil25@mail.ru
The Journal of Organic Chemistry
|July 3, 2010
Summary
A new fluorocyanation method for enamines was developed. This reaction uses N-F reagents to fluorinate double bonds and cyanide to trap intermediates, creating novel fluorinated compounds.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- Enamines are versatile synthetic intermediates.
- Fluorination and cyanation are important functionalization reactions in organic synthesis.
Purpose of the Study:
- To describe a novel method for the direct fluorocyanation of enamines.
- To explore the reactivity of enamines towards electrophilic fluorination and nucleophilic cyanation.
Main Methods:
- The reaction involves the use of N-F reagents, such as Selectfluor or N-Fluorobenzenesulfonimide (NFSI), for the fluorination step.
- A cyanide nucleophile is employed to trap the resulting beta-fluoroiminium cationic intermediate.
Main Results:
- Successful synthesis of fluorocyanated enamines was achieved.
- The method provides a direct route to introduce both fluorine and cyano groups onto enamine scaffolds.
Conclusions:
- The described method offers an efficient pathway for the synthesis of valuable fluorinated organic compounds.
- This approach expands the synthetic toolbox for accessing complex molecules containing fluorine and cyano functionalities.
Related Concept Videos
01:26Synthesis 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.
01:14Aldehydes 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...
01:16Aldehydes 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.
01:19Types 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 instability of enols...
01:18Reactivity of Enols
Enols are a class of compounds where a hydroxyl group is attached to a carbon–carbon double bond, which implies that it is a vinyl alcohol. A carbonyl compound with an α hydrogen undergoes keto–enol tautomerism and remains in equilibrium with its tautomer, the enol form. Usually, the keto tautomer is present in a higher concentration than the enol tautomer due to the higher bond energy of C=O compared to C=C. Moreover, the direction of the keto–enol equilibrium is governed by factors like...
01:20Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions
Arenediazonium substitution reactions occur when the diazonium group is substituted by various functional groups such as halides, hydroxyl, nitrile, etc. For instance, arenediazonium salts react with copper(I) salts of chloride, bromide, or cyanide to form corresponding aryl chlorides, bromides, and nitriles. These reactions are named Sandmeyer reactions. Although the mechanism of this reaction is complicated, as illustrated in Figure 1, they are believed to progress via an aryl copper...