The use of enaminones as effective synthons for a directed C-H functionalization is reported. Proof-of-concept protocols have been developed for the Rh(III) -catalyzed synthesis of naphthalenes, ...based on the coupling of enaminones with either alkynes or α-diazo-β-ketoesters. Two inherently reactive functionalities (hydroxy and aldehyde groups) are integrated into the newly formed cyclic framework and a broad range of substituents are tolerated, rendering target products readily available for further elaboration.
•New halo-enaminones were synthesized in a very good yield and characterized.•Single crystal XRD was performed and analysed.•DFT simulations were performed to know their structural and electronic ...properties.•Non-linear optical properties were studied for the synthesized Enaminones.•Molecular docking and ADMET studies were done to prove their potency as CNS drugs.
Some new halo-enaminones (2b-2g) of (Z)-1-(((2-acetylphenyl)amino)methylene)naphthalen-2(1H)-one (2a) were successfully synthesized in a very good yield. They were characterized by spectroscopic techniques. The single crystal XRD analysis confirmed the structure, stereochemistry, and hydrogen bond interactions of the synthesized enaminones. Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) were employed to study theoretical attributes such as Structural analysis, Natural Bond Order analysis (NBO), Frontier molecular Orbital Analysis (FMO), Global and local reactivity descriptors, Molecular Electrostatic Potential (MEP) analysis, Absorption, Emission and Non-Linear Optical (NLO) properties. Molecular docking analysis revealed that all these compounds had an excellent binding energy of ∼ -12 kcal/mol, with the human Sirtuin 2 (SIRT2) protein (PDB ID: 5Y5N), which is predominantly expressed in the brain. In addition, ADMET analysis revealed that all of them have drug-like properties, Blood Brain Barrier (BBB) permeable, and are not P–Glycoprotein substrates, implying that they are potential Central Nervous System (CNS) drugs.
Display omitted
The enaminone scaffold is a versatile building block used in organic synthesis. The amine – alkene – carbonyl conjugated system, having both nucleophilic and electrophilic characteristics, allows for ...a highly reactive center, that can serve as a pharmacophore for molecules in drug development. Analogs with this moiety have an array of pharmacological responses such as antiviral, anti-inflammatory, antitumor, anticancer and anticonvulsant activities. Herein, this review provides insight of current synthetic methodologies that employ enaminones as intermediates and their preparations. Structure activity relationship studies of various enaminone analogs will be examined in this review as well.
Display omitted
•Enaminones are versatile scaffolds with various therapeutic activities.•Organic properties and synthetic pathways of enaminones.•Newly identified enaminones in recent years and their application in medicinal chemistry are summarized in the review.
A facile and efficient method for the synthesis of chromone-containing triarylmethane derivatives via a HFIP promoted tandem alkylation/annulation protocol of o-hydroxyaryl enaminones with ...chlorohydrocarbon is described. Employing DCM/HFIP as solvent, the reactions proceed smoothly at room temperature without any transition-metal catalyst, providing a variety of chromone-containing triarylmethanes in moderate to good yields. Moreover, the developed protocol reveals a broad substrate scope and good group tolerance.
Display omitted
Display omitted
A novel method for the direct conversion of enaminones to α-keto amides has been developed. This transformation involves an oxidative rearrangement of enaminones under free radical ...conditions. In the presence of KI, TBHP and octanoic acid, a series of α-keto amides were obtained in moderate to excellent yields. This reaction demonstrates excellent functional group compatibility, utilizes readily available materials, and is easy to perform. Additionally, when o-hydroxyphenyl enaminone was utilized as the substrate, the reaction yielded 3-iodochromone in a high yield.
Catalytic CH activation-initiated annulation reactions have emerged as a versatile strategy for the efficient construction of diverse ring structural units and complex cyclic molecules in synthetic ...chemistry. Herein, we describe a new Rh(III)-catalyzed CH activation-initiated transdiannulation reaction of N,N-dimethyl enaminones with gem-difluorocyclopropenes in the presence of H2O, enabling a facile and oxygen transfer access to ring-fluorinated tricyclic γ-lactones with a 6-5 ring-junction tetrasubstituted stereocenter. This approach features bond-forming/annulation efficiency, good functional group tolerance and complete regioselectivity, which may include a complex process consisting of Rh(III)-catalyzed C(sp2)H activation, cyclic alkene insertion, defluorinated ring-opening of gem-difluorocyclopropane, intramolecular oxygen transfer, intramolecular cyclization and oxidative hydration.
A new Rh(III)-catalyzed C-H activation-initiated transdiannulation reaction of N,N-dimethyl enaminones with gem-difluorocyclopropenes is reported for the first time, enabling a facile and complete regioselective access to ring-fluorinated tricyclic γ-lactones with a 6-5 ring-junction tetrasubstituted stereocenter in good yields. Display omitted
Gone fishing: When propiophenone and related ethyl ketones are treated with morpholine in the presence of K3PO4, chlorobenzene, and Ni(cod)2/PMe3 catalyst, a carbon–nitrogen bond is formed ...selectively at the β position (see scheme; cod=cycloocta‐1,5‐diene). Secondary amines were employed as substrates to give the corresponding β‐enaminones.
Gone fishing: When propiophenone and related ethyl ketones are treated with morpholine in the presence of K3PO4, chlorobenzene, and Ni(cod)2/PMe3 catalyst, a carbon–nitrogen bond is formed selectively at the β position (see scheme; cod=cycloocta‐1,5‐diene). Secondary amines were employed as substrates to give the corresponding β‐enaminones.
4-acyl-1,2,3-triazoles are an important and versatile chemical scaffold widely applied in medicinal chemists due to their interesting pharmacological properties. Acknowledging the constant need for a ...greener, simple and scalable methodology in medicinal chemistry, herein we report the synthesis of new 4-acyl-1,2,3-triazoles through the metal-free and solvent-free cycloaddition reactions between enaminones and aryl azides, obtaining yields of 41–77%. Based on experimental Hammett correlation and theoretical Quantum calculations data a reaction mechanism for 3-dipolar cycloadditions synthesis of 4-acyl-1,2,3-triazoles was proposed.
Display omitted
•New 4-acyl-1,2,3-triazoles were synthesized through 1,3-dipolar cycloaddition reaction.•Enaminones and aryl-azides were used as substrates for the metal and solvent-free methodology.•The mechanism of the reaction was experimentally investigated by the LFER.•The mechanism of the reaction was computationally investigated by DFT and LFER.
The reactions of N,N‐substituted enaminones with TEMPO leading to the synthesis of 2,2‐dimethyl pyrrolidine functionalized new enaminones have been established by Ni(II) catalysis. The interesting ...ring contraction on TEMPO as well as the enaminone C−N bond amination bring new tool for generating molecular diversity of enaminones in the amino group fragment.
The Ni(II)‐catalyzed ring contraction in TEMPO providing 2,3‐dimethyl pyrrolidine as well as the capture of this species with N,N‐dimethyl enaminones through transamination are realized for the practical synthesis of 2,3‐dimethyl pyrrolidine functionalized enaminones for the first time.
The rhodium(III)‐catalyzed C−H bond activation and vinylene transfer of enaminones with vinylene carbonate have been proposed for the synthesis of substituted 1‐hydroxy‐2‐naphthaldehydes in 49–84% ...yields. Several preliminary mechanistic studies and hydroxyl‐directed derivatization reactions of 1‐hydroxy‐2‐naphthaldehydes were also performed. This method offers an alternative approach for the synthesis of 1‐hydroxy‐2‐naphthaldehydes.
