Synthesis of substituted thiazolo[4,5-b]pyridines and other annulated heterocycles via SN2→Thorpe-Ziegler→Thorpe-Guareschi domino reactions

A new combinatorial method for the preparation of substituted thiazolo[4,5-b]pyridines, which utilizes cyanoacetamide, heterocumulenes (isothiocyanates, carbon bisulfide), and ethyl-4-chloroacetoacetate in a new S_N2→Thorpe-Ziegler→Thorpe-Guareschi domino reactions has been developed. The obtained thiazolo[4,5-b]pyridines were then used together with aldehydes and malononitrile in another Knoevenagel reaction→Michael reaction→hetero-Thorpe-Ziegler domino reaction for the synthesis of substituted 4,6-dihydro-5H-pyrano[2,3-d]thiazolo[4,5-b]pyridines.     

A new domino Knoevenagel-hetero-Diels-Alder reaction: an efficient catalyst-free synthesis of novel thiochromone-annulated thiopyranocoumarin derivatives in aqueous medium

An efficient catalyst-free synthesis of novel pentacyclic thiochromone-annulated thiopyranocoumarin derivatives is achieved via domino Knoevenagel-hetero-Diels-Alder reaction of 4-hydroxy dithiocoumarin and O-acrylated salicylaldehyde derivatives in H₂O as solvent. The products are formed in good yields with high regio- and stereo-selectivity.     

Synthesis of some complex pyrano[2,3-b]- and pyrido[2,3-b]quinolines from simple acetanilides via intramolecular domino hetero Diels-Alder reactions of 1-oxa-1,3-butadienes in aqueous medium

Some complex pyrano[2,3-b]- and pyrido[2,3-b]quinolines were synthesized from simple acetanilides via intramolecular domino hetero Diels-Alder reactions of 1-oxa-1,3-butadienes using water as solvent.     

Efficient [4+1]/[3+2+1] bis-cyclizations stereoselectively yielding unprecedented polyacyclic indeno-fused xanthenes

Concise and efficient [4+1]/[3+2+1] bis-cyclizations of o-phthalaldehyde with cyclic 1,3-dicarbonyls have been established for the stereoselective synthesis of unprecedented polycyclic indeno[2,1-l]xanthene derivatives. The multicomponent domino reaction (MDR, AB₂ type) is easy to perform by mixing inexpensive substrates in HOAc at room temperature. The present synthesis shows attractive properties such as the simple one-pot fashion, high bond-forming efficiency, and easy purifications. Up to two new rings and four sigma-bonds were achieved in these MDRs without using any metal catalysts.     

Solvent-free sonochemical one-pot three-component synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones

A rapid and efficient one-pot three-component protocol for the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones 4 and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 6 has been developed by domino coupling of phthalhydrazide, 1,3-diketones, and aldehydes under solvent-free conditions at 80 °C as well as under solvent-free ultrasound irradiation at room temperature promoted by (S)-camphorsulfonic acid.     

A domino approach for the synthesis of naphtho[2,1-b]furan-2(1H)-ones from azlactones

A domino approach to naphtho[2,1-b]furan-2(1H)-one derivatives from (Z)-4-arylidene-2-phenyl-5(4)-oxazolones (azlactones) and 2-naphthols catalyzed by p-TSA with reasonably moderate to high yields, has been developed. This protocol illustrates attractive features including a unique and convenient process.     

A new laccase-catalyzed domino process and its application to the efficient synthesis of 2-aryl-1H-benzimidazoles

The laccase-catalyzed domino reaction of o-phenylenediamine and benzaldehydes with aerial oxygen as the oxidant exclusively yields 2-aryl-1H-benzimidazoles in good to very good yields. It is easy to perform under very mild reaction conditions.     

Domino Knoevenagel hetero-Diels-Alder reactions: a stereoselective synthesis of sugar fused furo[3,2-b]pyrano[4,3-d]pyran derivatives

The O-prenyl derivative of a sugar aldehyde derived from d-glucose undergoes smooth intramolecular domino Knoevenagel hetero-Diels-Alder reactions with 1,3-diones to afford a novel class of carbohydrate analogues, cis-fused furopyranopyrans in good yields with a high degree of chemoselectivity. The stereochemistry of the products was assigned by NMR.     

Facile, four-component, domino reactions for the regioselective synthesis of tetrahydrobenzo[g]quinolines

Facile, four-component domino reactions of 2-hydroxy-1,4-naphthaquinone, aromatic aldehydes, methyl/ethyl acetoacetate and ammonium acetate in ethanol under microwave irradiation at 100 °C afforded tetrahydrobenzo[g]quinoline-5,10-diones regioselectively in good yields. This transformation presumably proceeds via α,β-unsaturated triketone generation/Michael addition/regioselective annulation via intramolecular condensation domino sequence.     

Domino reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with 2-(1-phenylalkylidene)malononitriles: synthesis of functionalized 6-(trifluoromethyl)-6H-dibenzo[b,d]pyrans and a rare case of [1,5] sigmatropic shift of the nitro group

A variety of functionalized 6-(trifluoromethyl)-6H-dibenzo[b,d]pyrans were easily synthesized in good yields under mild conditions by a domino reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with 2-(1-phenylethylidene)- and 2-(1-phenylpropylidene)malononitriles. In the latter case, intermediate 7-amino-10-methyl-10-nitro-9-phenyl-6-(trifluoromethyl)-10,10a-dihydro-6H-benzo[c]chromene-8-carbonitriles were isolated as a result of a rare [1,5] sigmatropic shift of the nitro group.     

Laccase initiated oxidative domino reactions for the efficient synthesis of 3,4-dihydro-7,8-dihydroxy-2H-dibenzofuran-1-ones

Laccase initiated domino reactions of cyclohexane-1,3-diones with catechols using air as an oxidant afford 3,4-dihydro-7,8-dihydroxy-2H-dibenzofuran-1-ones with yields ranging from 70% to 97%.     

l-Proline-catalyzed three-component domino reactions for the synthesis of highly functionalized pyrazolo[3,4-b]pyridines

A series of novel N,3-dimethyl-5-nitro-1-aryl-1H-pyrazolo[3,4-b]pyridin-6-amines was obtained in good yields from the domino reactions of N-methyl-1-(methylthio)-2-nitroprop-1-en-1-amine, aromatic aldehydes, and 3-methyl-1-aryl-1H-pyrazol-5-amines in ethanol in the presence of green catalyst, l-proline. This transformation involves the formation of two C–C and one C–N bonds leading to the creation of a six-membered ring in a one-pot operation.     

An efficient catalyst-free synthesis of novel benzo[a][1,3]oxazino[6,5-c]phenazine derivatives via one pot four-component domino protocol in water

A catalyst-free multicomponent reaction (MCR) capable of affording a wide range of novel benzo[a][1,3]oxazino[6,5-c]phenazine derivatives via one pot two-step domino protocol, in water is reported. Catalyst-free conditions along with green solvent system make the process ecofriendly as well as economical. Simple reaction conditions, easy work-up isolation, and purification of products are the significant advantages of the present protocol.     

Pd-catalyzed cross-coupling/heterocyclization domino reaction: facile access to anthra[2,3-b]furan-5,10-dione scaffold

A new facile route to the synthesis of 4,11-dimethoxyanthra[2,3-b]furan-5,10-dione and its novel 2-substituted derivatives was proposed. The developed scheme was based on a Pd-catalyzed cross-coupling/heterocyclization domino reaction of 3-bromo-2-hydroxy-4,11-dimethoxyanthraquinone with terminal alkynes.     

Rapid,clean and efficient one-pot synthesis of thiopyrano[2,3-b]quinolines via domino Michael addition/cyclization reactions

Rapid and efficient one-pot synthesis of thiopyrano[2,3-b]quinolines is described from the reaction of 3-formyl-quinoline-2-thiones with acrylonitrile using economical organic base Et₃N at room temperature. The reaction proceeded smoothly via domino Michael addition/cyclization reactions and did not require dry solvent, inert atmosphere and column chromatography purifications.     

New domino approach for the synthesis of 2,3-disubstituted benzo[b]furans via copper-catalyzed multi-component coupling reactions followed by cyclization

An efficient domino process for the construction of 2,3-disubstituted benzo[b]furans has been developed via copper-catalyzed three-component coupling reactions of salicylaldehydes, amines, and alkynes followed by base-assisted O-annulation reaction.     

Temperature dependent selective synthesis of linear 2-bromo and 2-alkoxyfuro[2,3-b]quinolines: reaction of 3-(2,2-dibromovinyl-)quinolin-2(1H)-ones with alcoholic KOH

Base promoted and temperature dependent reactions of 3-(2,2-dibromovinyl)quinolin-2(1H)-ones have been described. At 50 °C, the cyclization reactions afforded 2-bromofuro[2,3-b]quinolines in good yields. However, at elevated temperature (80 °C) the domino reaction proceeded affording 2-alkoxyfuro[2,3-b]quinolines via cyclization and nucleophilic substitution reactions.     

Synthesis of benzimidazo[2,1-b]benzothiazole derivatives through sequential Cu-catalyzed domino coupling and Pd-catalyzed Suzuki reaction

A variety of benzo[d]benzo[4,5]imidazo[2,1-b]thiazoles were efficiently and conveniently synthesized from the Cu-catalyzed domino coupling of o-dihaloarenes with 2-mercaptobenzimidazoles. The reaction is also applicable to a series of multi-functional substrates, affording the halo-containing products with excellent selectivity. The brominated products can further react with arylboronic acids under Pd catalysis to furnish the aryl-substituted benzimidazo[2,1-b]benzothiazole derivatives.     

A facile domino protocol for the stereoselective synthesis of trans-2,3-dihydrobenzofurans and cis-5,6-dihydrofuro[2,3-d]pyrimidines

A facile protocol for the stereoselective construction of trans-2,3-dihydrobenzofurans and cis-5,6-dihydrofuro[2,3-d]pyrimidines from the reactions of 2,2′-sulfonylbis(1,3-diarylprop-2-en-1-ones) with cyclic 1,3-diketones, viz. cyclohexane-1,3-diones, barbituric acid, and 2-thioxodihydropyrimidine-4,6(1H,5H)-dione in the presence of DBU in ethanol is described. This transformation presumably occurs via domino Michael addition-proton exchange-annulation via intramolecular displacement sequence.     

A solvent-free protocol for the synthesis of 3-formyl-2H-chromenes via domino oxa Michael/aldol reaction

A new solvent-free, TBD-catalyzed protocol for the synthesis of 3-formyl-2H-chromenes is presented. Substituted salicylaldehydes 1 and 3-methyl-2-butenal 2 in the presence of 10 mol % of TBD underwent a domino oxa Michael/aldol reaction to effectively yield the corresponding 2H-chromene derivatives 3. The methodology represents an improvement either in terms of efficiency and sustainability as a small amount of catalyst is required and the work-up procedure is simple and straightforward.