Divergent and Chemoselective Transformations of Thioamides with Designed Carbene Equivalents

The reactions of thioamides with ortho-nitro-substituted iodonium ylides proceeded under mild conditions to give enaminones or thiazoles, depending on the iodonium ylide used. This protocol allowed the use of protic solvents, including aqueous solutions, and therefore coupling reactions with complex molecules such as peptides or steroids were possible. A mild and efficient method for the synthesis of various iodonium ylides was established. DFT calculations suggested that the halogen bonding between a thioamide and iodonium ylide was important in this chemoselective coupling reaction. The potential use of enaminones conjugated with pharmaceuticals as prodrugs was also demonstrated.     

Copper-catalyzed chemoselective cross-coupling reaction of thioamides and α-diazocarbonyl compounds: Synthesis of enaminones

The development of operationally simple and cost-effective methods for CC bond formation reactions are highly important in pharmaceutical, agrochemical and material research. In this article we describe the first copper-catalyzed cross-coupling reaction of thioamides with acceptor/acceptor-substituted and acceptor-only substituted α-diazocarbonyl compounds to yield enaminones. The reaction shows broad substrate scope in terms of thioamides and diazocarbonyl compounds. Primary, secondary and tertiary thioamides all give enanminones when reacted with α-diazodiesters, α-diazoketoesters, α-diazodiketones, α-diazoketoamides, α-diazoesteramides, α-diazoketosulfones and α-diazomonoketones.     

One-pot synthesis of isoxazoles from enaminones: an application of Fe(II) as the catalyst for ring expansion of 2H-azirine intermediates

We report an application of FeCl₂ as an inexpensive, nontoxic, and efficient catalyst in a clean ring expansion reaction of 2H-azirine derivatives, an intermediate formed through the PhI(OAc)₂-mediated azirination of readily available enaminones. An alternative one-pot protocol for the synthesis of various substituted isoxazoles from their corresponding enaminones has been further established based on this reaction, and herein described.     

Enantioselective organocatalytic domino synthesis of tetrahydropyridin-2-ols

The asymmetric synthesis of tetrahydropyridin-2-ols from enals and enaminones is described. The organocatalytic domino reaction involves a Michael addition-hemiaminalization sequence using the J?rgensen-Hayashi catalyst. Dehydration or oxidation leads to the corresponding 1,4-dihydro-pyridines or 3,4-dihydropyridin-2-ones in a one-pot fashion.     

Sulfonic Acid Functionalized Nano Γ-Al2O3: a New,Efficient, and Reusable Catalyst for Synthesis of Thioamides

Abstract

Sulfonic acid functionalized nano γ-Al₂O₃ is easily prepared by the reaction of nano γ-Al₂O₃ with 1,3-propane sulfone. This reagent can be used as an eficient catalyst for the synthesis of thioamides. This new method consistently has the advantages of excellent yields and short reaction times. Further, the catalyst can be recovered for several times.     

Regioselective synthesis of 3-arylamino- and 5-arylaminoisoxazoles from enaminones

A highly regioselective synthesis of 3-arylamino- and 5-arylaminoisoxazoles from enaminones based on reaction condition selection is reported. 3-Arylaminoisoxazoles were produced by treating enaminones with aqueous hydroxylamine in DMF at 100 °C, whereas 5-arylaminoisoxazoles were synthesized by subjecting enaminones to aqueous hydroxylamine in the presence of KOH and TBAB in water under reflux. A mechanism for the regioselective synthesis of 3-arylamino- and 5-arylaminoisoxazoles is proposed.     

Pd-catalyzed allylic alkylation of thioamides

This work describes the first Pd-catalyzed allylic alkylation of thioamides. Various thioamides were efficiently α-allylated in high yields and with excellent selectivity for monoallylation under mild reaction conditions. The process not only provides a facile method for the synthesis of functionalized thioamides, but also presents a useful transformation for synthetically important thioamides.     

A simplified catalytic system for direct catalytic asymmetric aldol reaction of thioamides; application to an enantioselective synthesis of atorvastatin

A new catalytic system was developed for the direct catalytic asymmetric aldol reaction of thioamides. The new lithium-free Cu catalyst (second-generation catalyst) exhibited enhanced catalytic efficiency over the previously developed catalyst comprising [Cu(CH₃CN)₄]PF₆/Ph-BPE/LiOAr (first-generation catalyst), which required a tedious catalyst preparation process. In the reaction with the second-generation catalyst, the intermediate Cu-aldolate functioned as a Brønsted base to generate thioamide enolate, efficiently driving the catalytic cycle. The present aldol methodology culminated in a concise asymmetric synthesis of atorvastatin (Lipitor^®: atorvastatin calcium), a widely prescribed HMG-CoA reductase inhibitor for lowering low-density lipoprotein cholesterol.     

An Efficient Synthesis of Pyrroline‐Fused Acridine Derivatives Catalyzed by Silica Sulfuric Acid

A simple and efficient synthesis of pyrrolo[2,3,4‐kl]acridine‐1‐one derivatives via the cascade reaction of isatins with enaminones catalyzed by silica sulfuric acid (SSA) has been established. In this reactions, SSA shows a highly catalytic nature: easy to handle procedure, short reaction time, recycle exploitation, insensitivity to air and moisture, and excellent isolated yields. The catalyst could be recycled at least five times.     

The first example of a diastereoselective thio-Ugi reaction: a new synthetic approach to chiral imidazole derivatives

The first example of a diastereoselective thio-Ugi reaction with chiral alpha-methylbenzylamine is described. The reaction results in formation of two diastereomers of thioamides, the major of which was isolated. We have found that under similar conditions stereochemical results of the thio-Ugi reaction are opposite to stereochemical results of the Ugi reaction. Several chiral thioamides were synthesized. The reaction of thioamides with ammonia results in substituted amidines, which can be cyclized to imidazole derivatives in aqueous HCl. The synthesis of chiral imidazole derivatives was elaborated. Using certain approaches, both isomers of a key synthon in the synthesis of SB203386 (an orally bioactive HIV-1 protease inhibitor) were prepared. The scope, limitations, and stereochemistry of the approach are discussed.     

Synthesis of 1,3-benzothiazines by intramolecular dehydrogenative C–S cross-coupling in a flow electrolysis cell

Dehydrogenative cyclization of thioamides is an attractive approach for the synthesis of S-heterocycles. Reported herein is an electrochemical dehydrogenative cyclization reaction of N-benzyl thioamides in a flow electrolysis cell. The continuous-flow electrosynthesis has addressed the limitations associated with previously reported methods for the cyclization of alkylthioamides and provide a transition metal-and oxidizing reagent-free access to various functionalized 1,3-benzothiazines in good yields.     

Simple and Efficient One‐Pot,Three‐Component,Solvent‐Free Synthesis of β‐Enaminones via Sonogashira Coupling–Michael Addition Sequences

A simple, efficient, and environmentally friendly one‐pot, three‐component synthesis of β‐enaminones via Sonogashira coupling–Michael addition sequences under solvent‐free conditions has been reported. Also the synthesis of β‐enaminones has been achieved in high yields by the direct reaction of amines with ynones under solvent‐free conditions.     

Heteropolyacid anchored on SBA-15 functionalized with 2-aminoethyl dihydrogen phosphate: a novel and highly efficient catalyst for one-pot,three-component synthesis of trisubstituted 1,3-thiazoles

Heteropolyacid anchored on SBA-15 functionalized with 2-aminoethyl dihydrogen phosphate (SBA-15@AEPH₂-HPA) was synthesized as a novel and highly efficient heterogeneous mesoporous catalyst. Characterization of the as-synthesized catalyst was successfully performed using various techniques such as FT-IR, BET, small-angle XRD, SEM, EDX, TEM, TGA, ICP-OES and elemental analysis. The new catalyst revealed a superb catalytic activity towards the one-pot synthesis of a wide verity of trisubstituted 1,3-thiazole derivatives. This protocol involved the three-component reactions of arylglyoxals, cyclic 1,3-dicarbonyls and thioamides under mild reaction conditions. Surprisingly, the current methodology is far superior to the only literature precedent used in this regard. The most promising features which highlight the presented approach are: furnishing a very important class of pharmaceutically and biologically active 1,3-thiazoles in excellent yields within short reaction times, mildness of the reaction conditions, using water as the reaction media and facile catalyst reusability for at least nine successive runs without any appreciable loss of its activity. Importantly, the small-angle XRD analysis and TEM images of the 9th recovered catalyst clearly proved the privileged durability and stability of the introduced catalytic system, under the applied reaction condition.     

Solvent-free synthesis of 6-unsubstituted dihydropyrimidinones using 2-pyrrolidonium bisulphate as efficient catalyst

A one-pot three-component Biginelli-like reaction of enaminones, aldehydes with urea/thiourea in the presence of 2-pyrrolidonium bisulphate as an acidic ionic liquid catalyst for the preparation of 6-unsubstituted dihydropyrimidinones is described. The excellent yield, short reaction time, simple procedure and avoidance of the use of organic solvents are some advantages of this method.     

Green synthesis of 1,2,4-thiadizoles from thioamides in water using molecular oxygen as an oxidant

We present here an efficient green process for the synthesis of 1,2,4-thiadiazoles via iodine-catalyzed,oxidative dimerization of thioamides in water using molecular oxygen as a terminal oxidant. Under the optimized reaction conditions, aryl thioamides produced 3,5-diaryl-1,2,4-thiadiazoles in good to excellent yields. Alkyl thioamides and substituted thioureas could also provide corresponding 1,2,4-thiadiazole products.     

One pot three component synthesis of spiro [indolo-3,10’-indeno[1,2-b]quinolin]-2,4,11’-triones as a new class of antifungal and antimicrobial agents

A simple and efficient three component procedure has been developed for the synthesis of highly substituted spiro[indolo-3,10'-indeno[1,2-b]quinolin]-2,4,11'-triones by one pot three component condensation of enaminones, isatin and indane-1,3-dione in ethanol:water (1:1) in presence of ceric ammonium nitrate (CAN) as catalyst. This method provides several advantages such as lesser reaction time, high yield of products and operational simplicity. The antimicrobial activity of some of the compounds has been investigated against six microbial strains, some of the tested compounds showed good antimicrobial activity.     

An Environmentally Benign Catalytic Method for Versatile Synthesis of 1,4-Dihydropyridines via Multicomponent Reactions

The synthesis of diverse 1,4‐dihydropyridines have been achieved via the multicomponent reactions of aldehydes, enaminones and amines. The reactions have been smoothly performed in water to provide all products with moderate to excellent yields by using lactic acid as a green catalyst.     

Studies with enaminones and enaminonitriles: synthesis of 3-aroyl and 3-heteroaroyl-pyrazolo-[1,5-a]pyrimidines

The reaction of electron rich aromatics with cyanoacetic acid and acetic anhydride afforded 3-oxoalkanenitriles. Indium trichloride was used as a Lewis acid catalyst when the aromatic ring was not sufficiently reactive. The synthesized 3-oxoalkanenitriles were subsequently condensed with dimethylformamide dimethylacetal (DMFDMA) to yield enaminones that reacted readily with hydrazine hydrate to yield 4-aroylpyrazole-3-amines. The 4-aroylpyrazole-3-amines were condensed with enaminones to yield 3-aroylpyrazolo[1,5-a]pyrimidines.     

Synthesis of 3-keto-quinolines from enaminones,anilines and DMSO: Transition metal free one pot cascade

An efficient and transition metal-free approach for the synthesis of functionalized 3-ketoquinolines from readily available anilines, enaminones and DMSO in the presence of K₂S₂O₈ has been conducted. This one pot tandem reaction proceeds through [3+2+1] cycloaddition reaction involving DMSO, enaminones and amines. In this environmental benign approach, DMSO acts as both a one carbon source and the solvent. A broad range of variously substituted amines and enaminones are successfully employed in this one pot tandem process to access a broad range of substituted 3-ketoquinolines.     

Pyridine-mediated, one-pot, stereoselective synthesis of acyclic enaminones

A new one-pot, three-component reaction of phenacyl pyridinium bromides, various primary aromatic amines, and phenyl glyoxal or ethyl glyoxalate for the stereoselective synthesis of acylic enaminones in good chemical yields is described.