Molecular diversity of triphenylphosphine promoted reaction of electron-deficient alkynes and arylidene Meldrum acid (N,N'-dimethylbarbituric acid)

The three-component reaction of triphenylphosphine, dimethyl hex-2-en-4-ynedioate and arylidene N,N'-dimethylbarbituric acids in dry methylene dichloride at room temperature afforded trans-1,3-disubstituted 7,9-diazaspiro[4.5]dec-1-enes in good yields and with high diastereoselectivity. However, the similar three-component reaction with arylidene Meldrum acids resulted in a mixtures of cis/trans-1,2-disubstituted 7,9-dioxaspiro[4.5]dec-1-enes. Additionally, the three-component reaction of triphenylphosphine, dimethyl but-2-ynedioate and arylidene Meldrum acids gave polysubstituted 5-(triphenyl-λ⁵-phosphanylidene)cyclopenta-1,3-dienes. A plausible reaction mechanism was proposed for the formation of various products with different regioselectivity and diastereoselectivity.     

Synthesis of imidazo[1,2a]pyridines via three-component reaction of 2-aminopyridines, aldehydes and alkynes

A novel three-component reaction towards the synthesis of imidazo[1,2a]pyridines was independently developed based on 2-aminopyridines, aldehydes and alkynes, and thereby imidazo[1,2a]pyridines were obtained in acceptable yields by the CuSO4/TsOH catalyzed three-component reaction.     

Efficient synthesis of polycyclic dispirooxindoles via domino Diels–Alder cyclodimerization reaction

Three-component reactions of 4-cyanopyridine or ethyl isonicotinate with electron-deficient alkynes and isatins in dimethoxyethane at room temperature afforded spiro[3H-indole-3,2′-[2H,9aH-pyrido[2,1-b][1,3]oxazine] derivatives. Alternately, the similar three-component reaction at elevated temperature resulted in polycyclic dispirooxindole derivatives. The reaction mechanism is believed to involve sequential generation and cycloaddition of Huisgen's 1,4-dipole, and Diels–Alder cyclodimerization reaction. The similar three-component reactions containing acenaphthenequinone and phenanthrenequinone also afforded corresponding polyheterocyclic derivatives.     

Zinc chloride catalyzed three-component Ugi reaction: synthesis of N-cyclohexyl-2-(2-hydroxyphenylamino)acetamide derivatives

The ability of zinc chloride as a catalyst to promote the three-component Ugi reaction of 2-aminophenols, aliphatic or aromatic aldehydes, and cyclohexyl isocyanide in methanol at room temperature is described. The N-cyclohexyl-2-(2-hydroxyphenylamino) amide products are obtained in high yields. When N,N-dimethylformamide dimethyl acetal and triethyl orthoformate, as two new components of the three-component Ugi reaction are used instead of the aldehyde the reaction gives N-cyclohexyl-2-(dimethylamino)-2-(2-hydroxyphenylamino)acetamide and N-cyclohexyl-2-(2-hydroxyphenylamino)-2-ethoxyacetamide derivatives, respectively.     

A mild and highly efficient protocol for the one-pot synthesis of primary α-amino phosphonates under solvent-free conditions

Under solvent-free reaction conditions and in the presence of solid LiClO₄ a novel and mild protocol for the one-pot, three-component synthesis of primary α-amino phosphonates from an aldehyde, hexamethyldisilazane and a trialkyl phosphite is described giving high yields and having short reaction times. The same products are obtained in very low yields, when the three-component reaction is carried out under microwave irradiation and in the absence of solid LiClO₄. Examples of some prepared 1-aryl-N,N′-bis(arylidene)methanediamines are also described.     

Synthesis of the functionalized spiro[indoline-3,5′-pyrroline]-2,2′-diones via three-component reactions of arylamines,acetylenedicarboxylates, and isatins

In the presence of p-toluenesulfonic acid as the catalyst the three-component reactions of arylamines, acetylenedicarboxylates, and isatins showed very interesting molecular diversity. When equal amount of arylamine was used, the three-component reaction resulted in the high yields of functionalized 3′-hydroxyspiro[indoline-3,5′-pyrroline]-2,2′-dione derivatives. On the other hand the functionalized 3′-N-arylaminospiro[indoline-3,5′-pyrroline]-2,2′-diones were also successfully prepared in satisfactory yields by using 2 M arylamine in the reaction.     

One-pot, three-component route to 2H-indazolo[2,1-b]phthalazine-triones

2H-Indazolo[2,1-b]phthalazine-1,6,11(13H)-trione derivatives were synthesized in a simple and efficient method from the three-component condensation reaction of phthalhydrazide, dimedone, and aromatic aldehydes under solvent-free conditions in excellent yields and short reaction times.     

A novel three-component reaction for the synthesis of N-cyclohexyl-3-aryl-quinoxaline-2-amines

Ferric perchlorate catalyzes the three-component condensation reaction of o-phenylenediamine, aromatic aldehydes, and cyclohexyl isocyanide to afford the corresponding N-cyclohexyl-3-aryl-quinoxaline-2-amines in good yields.     

Syntheses of N-sulfonyl-N,N-disubstituted amidines via a three-component free-radical coupling reaction of tertiary amines and arenesulfonyl azides with terminal alkynes

A facile and efficient synthesis of N-sulfonyl-N,N-disubstituted amidines has been achieved via a CuI-catalyzed three-component free-radical coupling reaction of tertiary amines and arenesulfonyl azides with terminal alkynes in the presence of azodiisobutyronitrile(AIBN).The reaction mechanism of this reaction has also been studied.     

Lanthanide(III)-catalyzed multi-component aza-Diels-Alder reaction of aliphatic N-arylaldimines with cyclopentadiene

The Ln(OTf)₃-catalyzed formal aza-Diels-Alder (or Povarov) reaction of cyclopentadiene with in situ generated N-arylimines containing enolizable protons is described. This three-component Povarov reaction generates highly functionalized C-2 aliphatic substituted tetrahydroquinolines, heterocycles that were previously inaccessible using the Povarov reaction, because of the instability of the intermediate aliphatic N-arylaldimine.     

An isocyanide-based three-component reaction: synthesis of fully substituted N-alkyl-2-triphenylphosphoranylidene glutarimides

A three-component condensation reaction between an isocyanide, an electron-deficient acetylenic ester and (ethoxycarbonylmethyl)triphenylphosphonium bromide efficiently provides fully substituted N-alkyl-2-triphenylphosphoranylidene glutarimides in a one-pot reaction without any activation or modification.     

One-pot three-component coupling reaction: solvent-free synthesis of novel 3-substituted indoles catalyzed by PMA-SiO2

Solvent-free PMA-SiO₂-catalyzed synthesis of 3-substituted indole derivatives by a one-pot three-component coupling reaction between aldehyde, N-methyl aniline and indole is described.     

Synthesis of fully substituted pyrano[2,3-c]pyrazole derivatives via a multicomponent reaction of isocyanides

The three-component reaction of the zwitterions generated from dialkyl acetylenedicarboxylate and isocyanides with 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one is described. The reaction afforded the corresponding special type of fully substituted pyrano[2,3-c]pyrazole derivatives in good yields without using any catalyst and activation.     

Highly anti–anti selective synthesis of bis-β-amino ketones via three-component direct Mannich-type reaction of terephthalaldehyde catalyzed by ZrOCl2·8H2O

At room temperature, zirconium oxychloride (ZrOCl₂·8H₂O) efficiently catalyzes the direct Mannich-type reaction of a variety of in situ generated bis-imines using terephthalaldehyde and anilines with ketones in a three-component reaction at room temperature. The reaction proceeds rapidly and affords the corresponding bis-β-amino ketones in good-to-high yields with good-to-excellent anti–anti selectivity.     

Distereoselective one-pot synthesis of pyrimidopyrimidines using sulfated tin oxide as a reusable catalyst： An extension of Biginelli-type reaction

The Biginelli-type compounds 4,5,8a-triarylhexahydropyrimido[4,5-d]pyrimidine-2,7（1H,3H）-diones were synthesized by a one-pot three-component reaction using sulfated tin oxide as a reusable catalyst. This method has the advantages of high yields, short reaction time, simple starting materials and reusability of catalyst for several times.     

Domino synthesis of fused hexacyclic imidazoquinolinoacridinones catalyzed by CuI/l-proline

A three-component reaction of 2-halogenated aromatic aldehydes, 1H-benzo[d]imidazol-5-amine and cyclohexane-1,3-diones is described, and gives imidazoquinolinoacridinone derivatives in good yields catalyzed by CuI/l-proline. This Domino reaction constructs a fused hexacyclic skeleton in one-pot containing two new rings, six new bonds and an Ullmann-type C–N bond coupling reaction.     

Straightforward access to 2-iminoisoindolines via three-component coupling of arynes, isocyanides and imines

A three-component coupling reaction of arynes, isocyanides and N-tosylaldimines has been developed to offer modest to high yields of diverse 2-iminoisoindolines in one step. Intermediacy of arynes in the coupling has been verified by the reaction of unsymmetrical arynes.     

Three-component sequential synthesis of N,N′-disubstituted 5-arylidenedihydropyrimidine-2,4-dione

A three-component sequential process consisting in (1) in situ formation of carbodiimides by Staudinger reaction, (2) reaction with 2-(bromomethyl)-3-aryl-2-propenoic acids, and (3) final cyclization of the resulting N-acylurea intermediates in order to obtain the synthesis of an array of N,N′-disubstituted 5-arylidenedihydropyrimidine-2,4-dione under mild conditions is presented.     

An easy and general protocol for multicomponent coupling reactions of aldehydes, amides, and dienophiles

An improved procedure for the three-component coupling reaction of aldehydes, amides, and dienophiles (AAD-reaction) has been developed. The use of microwave technology enables the endo-selective synthesis of N-acyl cyclohexenylamines via condensation of readily available aldehydes and amides, and subsequent Diels-Alder reaction with electron-deficient dienophiles in significantly improved yields. Advantageously, there is no need of employing additional solvents and reaction times are drastically reduced compared to similar thermal reactions.     

A simple one-pot, three-component, catalytic, highly enantioselective isoxazolidine synthesis

The highly chemo- and enantioselective organocatalytic three-component reaction between N-arylhydroxylamines, aldehydes and α,β-unsaturated aldehydes is presented; the reaction gives access to isoxazolidines in high yields with >25:1 dr and 91-99% ee.