Synthesis of highly functionalized piperidines by one-pot multicomponent reaction using tetrabutylammonium tribromide (TBATB)

Tetrabutylammonium tribromide (TBATB) has been found to be an efficient catalyst for the one-pot synthesis of highly substituted piperidines through a combination of 1,3-dicarbonyl compounds, aromatic aldehydes, and various amines in ethanol at room temperature. Atom economy, good yields, environmentally benign, and mild reaction conditions are some of the important features of this protocol.     

A Polymer-Supported Phosphazine as a Stable and Practical Reagent in the Three-Component Synthesis of Substituted (Cyclopentadienyl)tricarbonylrhenium Complexes

A very stable heterogenized difunctional cyclopentadienyl-ring precursor , storable under ambient conditions, readily participates in the simultaneous formation of a η⁵ bond with a [fac-Re(CO)₃]⁺ species and a σ bond with heteroatom (halides, carboxylates) or carbon nucleophiles (boronic acids) to produce halo-, acyloxy-, or carbon-substituted cyclopentadienyl–Re(CO)₃ complexes in a one-pot reaction in yields of between 41 and 71 % [Eq. (1)]. No catalyst is required and unprotected (usually) sensitive functional groups are well tolerated.     

The multicomponent reaction of dimethoxycarbene, dimethyl butynedioate and electrophilic styrenes: an unprecedented synthesis of highly substituted cyclopentenone acetals

The zwitterionic species generated by the addition of dimethoxycarbene to dimethyl butynedioate is trapped by arylidenemalononitrile to yield cyclopentenone derivatives.     

Divergent synthesis of functionalized thioethers via multicomponent reaction of benzynes

Diverse functionalized thioethers were efficiently synthesized through the multicomponent reaction of benzynes, cyclic thioethers and different nucleophiles. Both inorganic salts (KF, KCl, KBr, and KSCN) and silylated reagents (TMSCN, TMSN₃, TMSCl) can be utilized as efficient nucleophiles for the reaction.     

Catalyst-free multicomponent Strecker reaction in acetonitrile

The multicomponent Strecker reaction using trimethylsilyl cyanide was accomplished without any type of Lewis acid. The reaction performed in acetonitrile as solvent gave excellent results for any class of aldehydes (aromatic or aliphatic), as well as amines (aromatic or aliphatic). In many cases, α-aminonitrile product was isolated pure after the usual work-up, with quantitative chemical yields. A comparison between different solvents indicated that acetonitrile is the best choice. The rate comparison using different Lewis acids showed that all of them catalyzed the reaction in a similar extent, the difference with the acid Lewis-free being minimal.     

One-pot synthesis of substituted indolines via a copper-catalyzed sequential multicomponent/C-N coupling reaction

One-pot synthesis of 2-(N-sulfonylimino)indolines has been developed. The procedure combines the copper-catalyzed three-component reaction of sulfonyl azides, o-bromophenylacetylenes, and amines and the copper-catalyzed intramolecular C-N coupling in one sequence, which afforded the products in moderate to good yields. The resulting 2-(N-sulfonylimino)indolines could be easily transformed to pharmaceutically valuable oxindoles (indolin-2-ones).     

A new ‘one-pot’ synthesis of 2-substituted 3-nitro pyrrolidines through a multicomponent domino reaction

An efficient ‘one-pot’ synthesis of the title compounds based on a multicomponent domino reaction between imines and 3-nitro-1-propanol methanesulfonate has been developed.     

Straightforward stereoselective synthesis of polyfunctionalised cyclohexenols using a multicomponent approach

An intramolecular Ugi 5-centre-4-component reaction (U-5C-4CR) followed by a palladium-catalysed ring-opening has been employed to transform oxabicycloheptene-based β-amino acids into two families of regioisomeric polyfunctionalised cyclohexenols. The whole process is completely stereoselective and enantiomerically pure products are obtained in high overall yields.     

Synthesis of functionalized iminolactones via an isocyanide-based three-component reaction

A three-component reaction of the zwitterions generated from isocyanides and dialkyl acetylenedicarboxylate with 1-(4-bromophenyl)-2-thiocyanatoethanone or 1-phenyl-2-thiocyanatoethanone is described. The reaction afforded the corresponding special type of functionalized iminolactone derivatives in good yields at room temperature without using a catalyst.     

Water as the reaction medium for multicomponent reactions based on boronic acids

Water is a suitable medium for the Petasis-borono-Mannich multicomponent reaction. Salicylaldehyde, glyoxalic acid, glycoaldehyde and glyoxal were reacted with several boronic acids and different amines affording alkylaminophenols, 2H-chromenes, α-amino acids, α-amino alcohols and 2-hydroxylmorpholines in good to high yields. An efficient new one-pot method for the assembly of boron-heterocycles based on amino-acids, boronic acids and salicylaldehyde using water as the reaction media is presented. The mechanisms of these reactions were studied by means of DFT calculations, and the effect of solvent on the calculated energy barriers was addressed, for different aldehydes.     

Facile synthesis of highly functionalized stable ketenimines by a three-component reaction of alkyl isocyanides, dialkyl acetylenedicarboxylates and ethyl carbazones

Abstract  The reactive intermediate generated by the reaction of alkyl isocyanides and dialkyl acetylenedicarboxylates was trapped by ethyl carbazones to produce stable ketenimine derivatives in good yield. The reaction is characterized by mild conditions, high selectivity, and tolerance to various functional groups. Graphical abstract        

A new,convenient and expeditious synthesis of 4-alkyl-5-methyl-1H-pyrazol-3-ols in water through a multicomponent reaction

A new, simple and efficient synthesis of 4-alkyl-5-methyl-1H-pyrazol-3-ols in water by a two-pot four component reaction of ethyl acetoacetate, hydrazine hydrate, aldehyde and ketone in presence K₂CO₃ as the catalyst is described. Use of water as the reaction medium, operational simplicity, mild reaction conditions, application of a cost-effective, nontoxic and easily available catalyst with auto-tandem catalysis, wide substrate scope, easy workup and purification process make the protocol highly attractive.     

Organic Reaction in Water: A Highly Efficient and Environmentally Friendly Synthesis of Spiro Compounds Catalyzed by L‐Proline

We have developed a clean, simple and efficient method for the synthesis of spiro compounds by three‐component reaction of isatins (=1H‐indole‐2,3‐diones) or acenaphthylene‐1,2‐dione, 1,3‐diphenyl‐1H‐pyrazoles‐5‐amines, and tetronic acid (=furan‐2,4‐(3H,5H)‐dione or 2‐hydroxy‐1,4‐naphthoquinone in the presence of a catalytic amount of L ‐proline in aqueous media. The advantages of this procedure are mild reaction conditions, high yields of products, operational simplicity, and easy workup procedures employed.     

Asymmetric synthesis of the tricyclic core of cyathin diterpenoids via intramolecular Heck reaction

The enantioselective synthesis of the ketones 3 which displays the carbon core of NGF-inducing cyathane diterpenes is described. The key tricyclic trienone 22 was assembled in 13 steps from Michael adduct (R)-8a via intramolecular Heck cyclization of the chiral triflate 21. The trienone 22 was further elaborated into ketone 3 through trimethylaluminum-promoted expansion of the C-ring with trimethylsilyldiazomethane.     

A fast route for the synthesis of tetrazolyl oximes by a novel multicomponent reaction between Z-chlorooximes,isocyanides and trimethylsilyl azide

A library of twenty variously decorated 1,5-disubstituted-(1H-tetrazol-5-yl)methanone oximes was prepared in one single synthetic step exploiting the combination of (Z)-chlorooximes, isocyanides and trimethylsilyl azide. The formal [3+1] cycloaddition between isocyanides and nitrile N-oxides with respect to the [3+1] cycloaddition between isocyanides and azides prevails, while the direct attack of azide onto nitrile N-oxides remains competitive. Finally, an intramolecular cyclization of a (1H-tetrazol-5-yl)methanone oxime to a benzoisoxazole tetrazole is reported for the first time.     

Efficient Synthesis of Tetrahydropyrimidines and Pyrrolidines by a Multicomponent Reaction of Dialkyl Acetylenedicarboxylates (=Dialkyl But‐2‐ynedioates), Amines,and Formaldehyde in the Presence of Iodine as a Catalyst

Iodine was explored as an efficient catalyst for the synthesis of tetrahydropyrimidines 4 and pyrrolidines 5 by a multicomponent reaction of dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates) 1 , amines 2 , and HCHO 3 at room temperature (Scheme). When the molar ratios of these substrates were 1 : 2 : 4 and 1 : 1 : 4, tetrahydropyrimidines and pyrrolidines were formed, respectively. The products were obtained in high yields (73–85%) within a short period of time (25–35 min).     

Synthesis of highly functionalized pyrroles from primary amines and activated acetylenes in water

Stable derivatives of pyrroles were prepared using multicomponent reactions of dialkyl acetylenedicarboxylate,primary amine and propiolate in the presence of N-methylimidazole in water at room temperature in good yields.     

Organocatalytic enantioselective multicomponent cascade reaction: facile access to tetrahydropyridines with C3 all-carbon quaternary stereocenters

A novel organocatalytic asymmetric multicomponent cascade reaction for the synthesis of valuable tetrahydropyridines has been developed. The merit of this cascade process is highlighted by its high efficiency of producing five new bonds and an all-carbon quaternary stereocenter in one operation, which otherwise is a big challenge to access by traditional strategies.     

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.