Efficient and mild synthesis of functionalized 2,3-dihydrofuran derivatives via domino reaction in water

An efficient and mild method for the synthesis of functionalized tricyclic 2,3-dihydrofurans, bicyclic 2,3-dihydrofurans, and other tetrasubstituted 2,3-dihydrofurans by domino reaction of 1,3-dicarbonyl compounds and α-bromonitroalkenes with a large substrate scope and excellent diastereoselectivity (only trans isomers) in moderate to excellent yield (up to 96%) has been reported.     

Organocatalytic asymmetric domino aza-Michael-Mannich reaction: synthesis of tetrahydroimidazopyrimidine derivatives

Highly substituted tetrahydroimidazopyrimidine derivatives with three chiral centers have been synthesized for the first time using an organocatalytic asymmetric domino aza-Michael-Mannich reaction of α,β-unsaturated aldehydes and N-arylidene-1H-imidazol-2-amines. This efficient approach furnishes the products in good yields (42-87%) with excellent stereoselectivities (>20:1 dr, up to >99% ee).     

Facile access to pyrazolines via domino reaction of the Huisgen zwitterions with aziridines

A novel, efficient, and general domino reaction of 2-acylaziridines with the Huisgen zwitterions to furnish 2-pyrazoline rings is described. A possible mechanism for the domino sequence is proposed.     

Direct access to 1,4-benzothiazine 4,4-dioxides and 4-oxides via a domino reaction

The domino reactions of 2-fluoro benzensulfonyl acetonitrile and α-chloro oximes in the presence of Cs₂CO₃ in aprotic high boiling point solvents have been achieved to provide isoxazole?fused 4H-1,4-benzothiazine-4,4-dioxides via an unprecedented transition metal-free one-pot addition/cyclization process. The tunable synthesis of either isoxozolo-1,4-benzothiazin-4-oxides or their precursor 5-aminoisoxazoles can be controlled depending on the solvent selection. The observed products were characterized by means of (IR, ¹H, ¹³C NMR and HRMS) and physical methods.     

Three-component domino reaction synthesis of highly functionalized bicyclic pyrrole derivatives

An efficient one-pot synthesis of highly functionalized bicyclic pyrrole derivatives by a three-component domino reaction of heterocyclic ketene aminals (HKAs), arylglyoxal monohydrate, and indoles in ethanol medium catalyzed by acetic acid is described. In this procedure, three sigma bonds were formed simultaneously. The present synthesis features excellent regio-selectivity, easy purification as well as simple starting materials.     

Acid-mediated domino reaction of ortho-carbonylated alkynyl-substituted arylaldehydes with phenols: Rapid access to fused indeno[2,1-c]chromen-7-one derivatives

Acid-mediated domino reaction of ortho-carbonylated alkynyl-substituted arylaldehydes with phenols is described. The implement of this reaction can provide directly a variety of tetracyclic indeno[2,1-c]chromen-7-one products in good yields. The mechanism was proposed to be a domino indanone ring formation/ortho-alkylation of phenols/dehydrated cyclization for the formation of polycyclic skeleton. In addition, several interesting dimeric products containing a pentacyclic scaffold were also afforded stereoselectively albeit in moderate yields. The present transformations feature the use of simple acid catalyst, short reaction time and good substrate scope.     

Rapid and easy access to indoles via microwave-assisted Hemetsberger-Knittel synthesis

Hemetsberger-Knittel indole synthesis can be carried out under microwave activation. The optimum reaction conditions were found by using different solvents and by varying irradiation times and temperature. After 10 min of microwave irradiation, high conversion into the corresponding indole products was achieved without formation of any side products.     

Enantioselective access to tetrahydropyrano[2,3-c]pyrazoles via an organocatalytic domino Michael-hydroalkoxylation reaction

An asymmetric domino Michael-hydroalkoxylation reaction of trans-α-alkynyl-nitroolefins with N-arylpyrazolinones has been accomplished using a chiral bifunctional squaramide catalyst. Under the organocatalytic method, a broad range of tetrahydropyrano[2,3-c]pyrazoles with an exocyclic alkene at the C-6 position were prepared in high yields and excellent stereoselectivities. The presence of an exocyclic double bond and nitro group in the pyranopyrazoles provide a wide scope for further structural transformations.     

Convenient synthesis of hexasubstituted benzene derivatives via DABCO promoted domino reaction of arylidene malononitrile and dialkyl but-2-ynedioate

A convenient synthetic protocol for the hexasubstituted benzene derivatives was successfully developed by DABCO promoted domino reaction of arylidene malononitrile with two molecules of dialkyl but-2-ynedioates. The domino reaction resulted in tetraalkyl 6-cyano-[1,1′-biphenyl]-2,3,4,5-tetracarboxylates in good to high yields. This formal [2 + 2 + 2] cycloaddition was believed to proceed with sequential nucleophilic addition, Michael addition, annulation and aromatization processes.     

A multi-component domino reaction for the direct access to polyfunctionalized indoles via intermolecular allylic esterification and indolation

A novel multi-component reaction for the synthesis of polyfunctionalized indoles and bis-indoles has been established. The reaction pathways were controlled by varying enamines with different substitution patterns to give polyfunctionalized indoles and bis-indoles selectively. The reaction proceeds at a fast speed within 15-30 min with water as the major byproduct, which makes work-up convenient.     

An approach to the synthesis of dimeric resveratrol natural products via a palladium-catalyzed domino reaction

A route for the rapid assembly of the carbon framework of several resveratrol natural products is presented. A palladium-catalyzed domino reaction of bromostilbene derivative 6 and tolane 7, involving two sequential Heck coupling reactions, provides access to the benzofulvene-based core of various resveratrol-derived natural products. The carbon skeleton of pallidol and its congeners is achieved by a Lewis acid-induced Nazarov-type oxidative cyclization of 9.     

De novo synthesis of sugar-aza-crown ethers via a domino Staudinger aza-Wittig reaction

A short and highly efficient route to sugar-aza-crown (SAC) ethers has been developed. The key step of the transformation is a one-pot cyclodimerization of C-glycosyl azido aldehydes via a domino Staudinger aza-Wittig reaction. This process allows the preparation of various orthogonally protected SAC ethers, from both alpha- and beta-C-glycosyl azido aldehydes.     

Copper-catalyzed domino reaction of carbodiimides and benzoic acid derivatives for the synthesis of quinazolinediones

Quinazolinediones were obtained from 2-iodobenzoic acids and carbodiimide derivatives under mild reaction conditions via a copper-catalyzed domino reaction. The absence of an external base was essential to avoid the generation of amide by-products. Both alkyl- and aryl-substituted carbodiimides gave the corresponding quinazolinediones. However, the use of aryl-substituted carbodiimides resulted in low yields due to an undesired elimination process.     

New practical access to 2-azatryptophans and dehydro derivatives via the Wittig-Horner reaction

The Wittig-Horner reaction of protected 3-formylindazoles 1 with (±)-N-(benzyloxycarbonyl)-α-phosphonoglycine trimethyl ester 2 has been developed as a new practical synthesis of dehydro 2-azatryptophans and amino acid derivatives. The preparation of 5-bromo-3-formylindazole is discussed.     

Rapid access to novel 2-alkylthiopyrimidine derivatives and attempt of their Tacrine analogs synthesis

A variety of novel 2-alkylthiopyrimidines were synthesized through simple condensation of arylidenemalononitriles with different 2-alkylthiouronium halide derivatives catalyzed by anhydrous potassium carbonate (K₂CO₃). The reactions have been carried out under mild conditions in i-PrOH, and the products were obtained in moderate to good yields with a simple work-up method. Subsequently, some examples of these compounds have been converted into Tacrine analogs by applying the Friedländer reaction.     

Efficient synthesis of 2-imino-1,2-dihydroquinolines and 2-imino-thiochromenes via copper-catalyzed domino reaction

A domino approach to 2-imino-1,2-dihydroquinolines and 2-imino-thiochromenes from sulfonyl azides, alkynes, and 2-acyl anilines or the potassium salt of 2-mercapto-benzaldehyde has been developed. This one-pot method is efficient and versatile.     

Facile synthesis of benzo-fused 2,8-dioxabicyclo[3.3.1]nonane derivatives via a domino Knoevenagel condensation/hetero-Diels-Alder reaction sequence

A facile two-step synthesis of a series of benzo-fused 2,8-dioxabicyclo[3.3.1]nonane derivatives is described, featuring a domino Knoevenagel condensation/intramolecular hetero-Diels-Alder reaction sequence.     

A facile method for synthesis of polysubstituted naphthalene derivatives through pyrrolidine catalyzed domino reaction

A novel synthetic method for polysubstituted naphthalene derivatives via a pyrrolidine-mediated cascade Michael/Henry reaction was developed, in which easily prepared 2-(2-oxoethyl)benzaldehydes and nitroalkenes were employed as the starting materials. The reaction consists of four consecutive reactions that include a cascade Michael/Henry reaction, a dehydration reaction, and an aromatization reaction in one pot to afford synthetically important naphthalene derivatives with moderate yields.     

Direct access to anthranilic acid derivatives via CO2 incorporation reaction using arynes

CO2 was found to be directly convertible into anthranilic acid derivatives of great synthetic value through a three-component coupling using arynes and amines. Zwitterions arising from nucleophilic attack of amines to arynes serve as key intermediates in the coupling.