Enamine Derivatives Research Articles

A general and efficient method for synthesis of enaminones and enamino esters catalyzed by NbCl5 under solvent-free conditions

A general and simple procedure was developed for the synthesis of β-enaminones and β-enamino esters by reacting 1,3-dicarbonyl compounds with amines in the presence of catalytic amounts of niobium pentachloride. The reaction proceeds smoothly at room temperature under solvent-free conditions and leads to chemo- and regioselective formation of enamine derivatives in high to excellent yields.

EfficientN‐Alkyl Enamination of 3‐(Thiobenzoyl)pyrrolo[2,3‐b]quinoxalin‐2‐one,E/ZIsomerisation of the Reaction Products and Potential Fluorescent Sensors for ­Zinc(II) Ion

AbstractAn efficient and rapid procedure for theN‐alkyl enamination from thioketones to push–pull (E/Z)‐enamine derivatives is reported. The starting thioketone2was obtained by regioselective thionation of 3‐benzoylpyrrolo[2,3‐b]quinoxalin‐2‐one (1) with Lawesson's reagent (LR).1H NMR and X‐ray crystal structure analyses of 1‐aryl‐3‐(alkylaminophenylmethylidene)pyrrolo[2,3‐b]quinoxalin‐2‐ones3–6confirmed that theEdiastereoisomers predominated. Interconversion of the isolatedEform of3band4ainto theZconfiguration and theirE/Zequilibria in [D6]DMSO were studied by temperature‐dependent1H NMR spectroscopy. The photophysical properties of compounds1–6are also reported. We found that the non‐fluorescent compounds3a–6aare chemosensors for the zinc ion. Fluorescent titrations of these sensors with zinc(II) acetate showed that compound6ahas the best working range of zinc concentrations withKd= 3.77 00 ± 0.51 μM.

FeCl3-PTSA Co-Catalysed Highly Regio- and Stereo-Selective Synthesis of β-Functionalised Enamine Derivatives

β-Enaminone derivatives are useful synthetic precursors. β- N-Substituted ( E)-enaminones and β-N-substituted ( E)-aminoacrylates were synthesised with high regio- and stereo-selectivity via using the co-catalytic system of FeCl3/PTSA, which also provides a new way to the formation of C–O bond.

Dual-Specificity Phosphatase CDC25A/B Inhibitor Identified from a Focused Library with Nonelectrophilic Core Structure

Focused libraries of enamine derivatives with a nonacidic, nonelectrophilic core structure were screened for inhibitors of dual-specificity protein phosphatases, and an o-hydroxybenzyl derivative RE44 (10d) was identified as a selective inhibitor of CDC25A/B. This inhibitor induced cell-cycle arrest of tsFT210 cells at the G2/M phase and inhibited dephosphorylation of the CDC25B substrate CDK1. Unlike most quinone-based inhibitors, 10d does not generate reactive oxygen species.

Highly Regioselective AgNTf2-Catalyzed Intermolecular Hydroamination of Alkynes with Anilines

A facile and economic method for the fully regioselective and high-yielding protocol for the hydroamination of unsymmetrical internal alkynes under mild reaction conditions with AgNTf2 was developed. The materials are easily available from commercial vendors, to give synthetically useful enamine derivatives efficiently. This strategy is efficient to build complex structures from simple starting materials in an environmentally compatible fashion.

Bifunctional 2,5‐Diketopiperazines as Efficient Organocatalysts for the Enantioselective Conjugate Addition of Aldehydes to Nitroolefins

AbstractFour peptidomimics (3–6) containing the cis‐DKP‐1 or trans‐DKP‐2 scaffolds and either L‐Pro or D‐Pro were synthesized. DKP‐1 and DKP‐2 are bifunctional diketopiperazines formally derived from the head‐to‐tail cyclization of L‐aspartic acid and either (R)‐ or (S)‐2,3‐diaminopropionic acid, which feature aminomethyl and carboxymethyl side arms in the 3‐ and 6‐positions of the 2,5‐piperazindione ring. Peptidomimics (3–6) were tested as organocatalysts in the conjugate addition of several aldehydes to β‐nitrostyrene and (E)‐2‐(furan‐2‐yl)nitroethene with good to excellent diastereo‐ and enantioselectivities. Monte Carlo/Energy Minimization (MC/EM) conformational searches were performed on the four catalysts and their enamine derivatives with propanal to rationalize the observed stereoselectivity.

Enamines in Heterocyclic Synthesis: A Novel Simple and Efficient Route to Condensed Pyridazines

An efficient and easy preparation of enamine derivatives, via active methyl and methylene compounds by in situ-generated 1-(diethoxymethyl)piperidine, produced from the mixture of triethyl orthoformate/piperidine/DMF, are described. Some new pyridazinone derivatives have been synthesized from the reaction of enamines with hydrazine hydrate and cyanoacid hydrazide.

Facile Synthesis of Sulfonyl Amidines and β-Amino Sulfonyl Enamines under Transition-Metal-Free Conditions

Treatment of enamine and azide resulted in the formation of either sulfonyl amidine or β-amino sulfonyl enamine derivative in moderate to good yields. The reaction could proceed under catalyst-free conditions.

ChemInform Abstract: Nucleophilic α‐Arylation and α‐Alkylation of Ketones by Polarity Inversion of N‐Alkoxyenamines: Entry to the Umpolung Reaction at the α‐Carbon Position of Carbonyl Compounds.

AbstractThe efficient and transition metal free umpolung reaction by polarity inversion at the β‐position of N‐alkoxyenamines is characterized by mild conditions and simple transformation of ketones such as (I) into α‐substituted ketones (IV) without isolation of the intermediate enamine derivatives (II).

Effect of enamine derivatives on the rectal absorption of insulin in dogs and rabbits.

Enamine derivatives resulting from the reaction between ethyl acetoacetate and amino acids were found to promote rectal absorption of insulin in normal rabbits, with the enamine of sodium DL-phenylalanate being the most effective adjuvant tested. Results of glucose tolerance tests in fasted alloxan diabetic rabbits showed that after oral administration of glucose, insulin suppositories containing enamines derived from either sodium phenylalanine or leucine were able to lower the serum glucose level to within the normal range for more than 2.5 h. The absorption-promoting effect of the sodium DL-phenylalanate enamine on rectal absorption of insulin in dogs was studied in two different formulations, gelatin microenema and suppository. The gelatin microenema containing the insulin solution caused a greater increase in the plasma insulin level than that obtained after administration of an insulin suppository.

Insulin suppository: enhanced rectal absorption of insulin using an enamine derivative as a new promoter.

Insulin suppository: enhanced rectal absorption of insulin using an enamine derivative as a new promoter.

Fluorinated 2-benzoylcyclohexane-1,3-diones and their vinylogous acyl chlorides in the reactions with primary and secondary amines

The reaction of 5,5-dimethyl-2-[(3-fluoro- and 4-fluoro)benzoyl]cyclohexane-1,3-diones with primary and secondary amines affords their exocyclic enamine derivatives. Under similar conditions 5,5-dimethyl-2-(2-fluorobenzoyl)]cyclohexane-1,3-dione undergoes dehydrofluorination and intramolecular cyclization to give 3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthene-1,9-dione. The reaction of vinylogous substitution of the enol derivatives of the fluorinated 5,5-dimethyl-2-benzoylcyclohexane-1,3-diones (vinylogous acyl chlorides) with amines results in the formation of the endocyclic enaminoderivatives.

エナミン誘導体の極性転換による炭素‐炭素結合構築法

Umpolung chemistry has been the focus of research on organic synthesis due to its usefulness and unusual reactivity. Above all, umpolung of enamine property enables the formation of highly substituted carbon-carbon bonds and installation of aryl groups on sp3 carbon atoms, which are difficult to realize by normal enolate chemistry. This short review describes recent reports of the carbon-carbon bond formation by umpolung reactions of enamine derivatives.

Addition-substitution reactions of 2-thio-3-chloroacrylamides with carbon, nitrogen, oxygen, sulfur and selenium nucleophiles

Synthetically versatile conjugate addition of a range of carbon, nitrogen, oxygen, sulfur and selenium nucleophiles to the highly functionalised 2-thio-3-chloroacrylamides is described. The stereochemical and synthetic features of this transformation are discussed in detail. In most instances, the nucleophile replaces the chloro substituent with retention of stereochemistry. With the oxygen nucleophiles, a second addition can occur leading to acetals, while with the nitrogen nucleophiles, E-Z isomerism occurs in the resulting enamine derivatives. The ratio of the E/Z isomers can be rationalised on the basis of the substituent and the level of oxidation.

Gold(I)-Catalyzed Intramolecular Tandem Addition/Friedel−Crafts Reactions between Acyclic Enamides and 1-Arylalkynes

Electron-deficient acyclic enamine derivatives react with electron-rich 1-arylalkynes using cationic gold(I) species as catalysts in an intramolecular process to form annulated 1-amido-substituted indene derivatives as the major products. Yields for this process range between 21% and 98%. In some cases, a two-step process that includes a subsequent alkene isomerization is needed.

Synthesis and UV absorption of new conjugated quinoxaline 1,4-dioxide derivatives anticipated as tumor imaging and cytotoxic agents

New conjugated arylidine, enamine, and annelated pyrido derivatives of quinoxaline 1,4-dioxide were synthesized via utilization of an active allylic methyl group. Biodistribution studies were carried out by injecting a solution of an 125I derivative of an enamine-substituted quinoxaline 1,4-dioxide in normal and tumor-bearing mice. The uptake in solid tumor was over 6% of the injected dose per gram tissue body weight at 4 h post injection. These data revealed localization of the tracer in the tumor tissues with a high percentage sufficient to show a radiotherapeutic effect and showed that this is a promising tool for diagnosis. Also the radiotoxicity of the 125I-substituted compound on Ehrlich ascites carcinoma cells may encourage this behavior.

ChemInform Abstract: Cationic Three‐Component Coupling Involving an Optically Active Enamine Derivative. From Time Integration to Space Integration of Reactions.

AbstractA one‐pot sequential method is elaborated for the synthesis of chiral oxazole derivatives by reaction of chiral oxazole (I) with N‐acyliminium cation (II) followed by addition of a nucleophile.

Highly enantioselective Rh-catalyzed transfer hydrogenation of N-sulfonyl ketimines

Several imine species comprising N-sulfinyl and N-sulfonyl ketimine, oxime, and enamine derivatives were subjected to asymmetric transfer hydrogenation in an azeotropic mixture of formic acid/triethylamine. Among them, the Rh-catalyzed transfer hydrogenation of N-sulfonyl ketimine afforded the corresponding 1-arylalkylamines in excellent yield and with high enantioselectivity.

Cationic Three-component Coupling Involving an Optically Active Enamine Derivative. From Time Integration to Space Integration of Reactions

Abstract Three-component coupling of an N-acyliminium cation pool, an optically active 2-t-butyloxazole derivative, and a carbon nucleophile such as allyltrimethylsilane was effectively achieved by a rapid one-pot method at −78 °C and a flow microreactor method at 0 °C.

Ca(CF3COO)2: An efficient Lewis acid catalyst for chemo- and regio-selective enamination of β-dicarbonyl compounds

Abstract A relevant procedure has been developed for the synthesis of β-enaminoesters catalysed by Ca(CF 3 COO) 2 . The reaction of β-ketoesters with primary amines was efficiently carried out under solvent-free conditions at room temperature and led to chemo- and regio-selective formations of enamine derivatives in high yields.