Tandem Wittig-intramolecular Diels-Alder cycloaddition of ester-tethered 1,3,9-decatrienes under microwave heating

Intramolecular Diels-Alder (IMDA) cycloaddition of the ester-tethered 1,3,9,-decatrienes possessing a carbonyl substituent at C10 has been investigated under controlled microwave heating (MeCN, 180 °C) to afford a variety of 3,4,4a,7,8,8a-hexahydroisochromen-1-ones in 53-89% yields and in 64:36-79:21 ratios for the cis and trans isomers. Under the same microwave heating conditions, a tandem Wittig-IMDA cycloaddition, starting from the α-bromoacetates of 3,5-hexadien-1-ols and glyoxalate/phenylglyoxal hydrates in the presence of PPh₃ and 2,6-lutidine, has been demonstrated, furnishing 3,4,4a,7,8,8a-hexahydroisochromen-1-one adducts in 73-91% yields in favor of the cis isomers. During this tandem process, three consecutive carbon-carbon bonds in the end products were efficiently formed with the aid of microwave irradiation within short reaction times.     

Microwave-assisted tandem reactions for the synthesis of 2-hydrazolyl-4-thiazolidinones

A tandem method for the synthesis of 2-hydrazolyl-4-thiazolidinones (5) from commercially available materials in a 3-component reaction has been developed. The reaction connects aldehydes, thiosemicarbazides, and maleic anhydride, effectively assisted by microwave irradiation. The synthesis of a new type of compound, 2-hydrazolyl-5,5-diphenyl-4-thiazolidinone (7), obtained by treatment of thiosemicarbazone with benzil in basic media is also reported. HOMO/LUMO energies, orbital coefficients, and charge distribution were used to explain the proposed reaction mechanism.     

Microwave-assisted reactions of nitroheterocycles with dienes. Diels-Alder and tandem hetero Diels-Alder/[3,3] sigmatropic shift

Diels-Alder cycloaddition of 3-nitro-1-(p-toluenesulfonyl)indole 1 with dienes 2-6 under microwave irradiation in solvent-free conditions gave carbazole derivatives after elimination of the nitro group and in situ aromatization. While 3-nitro-1-(p-toluenesulfonyl)pyrrole 11 afforded indole derivatives, 4-nitro-1-(p-toluenesulfonyl)pyrazole 13 with cyclohexadiene 2 did not afford the expected cycloadduct but instead gave 1-cyclohexen-2-ylpyrazole 16. This process occurred by hydrolysis of the 1-(p-toluenesulfonyl) group, protonation of the diene and nucleophilic addition of the pyrazolate ion, as elucidated by computational studies. Reaction of nitroindole 1 with cyclohexadiene 2 afforded exclusively the endo stereoisomer (10endo) in a tandem hetero Diels-Alder/[3,3] sigmatropic shift, as determined by computational calculations.     

Microwave assisted one-pot tandem three-component synthesis of 2,4,5-triary 1-2-4-dihydro-3H- 1,2,4-triazol-3-one derivatives

This work described a one-pot tandem three-component synthesis of 2,4,5-triaryl-2,4-dihydro-3H- 1,2,4-triazol-3-ones using a simple reaction between phenylhydrazines, benzaldehydes and phenyl isocyanates under microwave irradiation and solvent-free conditions in good to excellent yields.     

Facile synthesis of phthalan derivatives via a Pd-catalyzed tandem hydroalkynylation,isomerization, Diels-Alder cycloaddition and aromatization reaction

A novel Pd-catalyzed tandem reaction involving hydroalkynylation,isomerization.Diels-Alder cycloaddition and aromatization reaction to produce phthalan derivatives in moderate yields is reported.The reaction is atom economical and occurs in a highly ordered fashion.The reaction mechanism is discussed.     

Tandem inverse electron demand Diels-Alder, retro-Diels-Alder and intramolecular Diels-Alder sequences: one-pot synthesis of diaza-polycycles

A new and straightforward methodology is described for the construction of complex nitrogen-containing polycycles from substituted 1,2,4-triazines and enamines, prepared in situ from carbonyl components and allylic amines. The transformation proceeds via a pericyclic reaction cascade (inverse electron demand Diels-Alder then retro-Diels-Alder then intramolecular Diels-Alder) forming the polycyclic systems in good to excellent yield and with high diastereoselectivity in a one-pot procedure. The scope and limitations of the methodology are described as are preliminary studies to extend its synthetic utility.     

A novel synthesis of 1,3,5-trisubstituted pyrazoles through a spiro-pyrazoline intermediate via a tandem 1,3-dipolar cycloaddition/elimination

The syntheses of an important class of hitherto unreported 1,3,5-pyrazoles, inspired by an unanticipated eliminatory ring opening are described. The reported pyrazole compounds were constructed through the Huisgen cyclization of 2-methylene-1,3,3-trimethylindoline and an in situ generated nitrile imine. The newly formed spiro-pyrazoline intermediate presumably then undergoes a ring opening/elimination process to afford a pyrazole, as evidenced by single X-ray crystal data. The current report constitutes the first formal observation of this kind of ring opening involving a spiro-pyrazoline intermediate.     

A novel four-component tandem protocol for the stereoselective synthesis of highly functionalised thiazoles

The reaction of bis(aroylmethyl) sulfides with aromatic aldehydes and ammonium acetate in 1:2:1 molar ratio under solvent-free microwave irradiation afforded predominantly a series of thiazoles, viz., 1-aryl-2-[5(Z)-5-arylmethylidene-2,4-diaryl-2,5-dihydrothiazol-2-yl]ethanones stereoselectively. This reaction presumably occurs via a Knoevenagel condensation-Michael addition-cyclocondensation-ring opening-ring closing Michael addition sequence. The intermediacy of (Z,Z)-2,2′-thiobis(1,3-diarylprop-2-en-1-ones) in the above transformation is demonstrated by their conversion to the thiazoles upon reaction with ammonium acetate under solvent-free microwave irradiation.     

Convenient ‘one-pot’ synthesis of 3,4-substituted tetrahydrothiophenes through tandem Michael-Henry and Michael-Michael reactions

In situ generated nitro alkenes underwent tandem Michael-Henry and Michael-Michael sequences leading to the ‘one-pot’ formation of 3,4-substituted tetrahydrothiophenes using the commercially available 1,4-dithiane-2,5-diol (the dimer of mercaptoacetaldehyde) or its 4-mercapto-2-butenoates derivatives as suitable bifunctional partners, respectively.     

Microwave-assisted regioselective olefinations of cyclic mono- and di-ketones with a stabilized phosphorus ylide

A number of cyclic mono- and di-ketones underwent regioselective olefination with (carbethoxyethylidene)triphenylphospharane under controlled microwave heating. The Wittig reaction of 4-substituted cyclohexanones or 1,2- and 1,4-cyclohexanediones with the ylide at 190 °C for 20 min in MeCN afforded the exocyclic olefins in >94:6 isomer ratios. On the other hand, the same reactions carried out at 230 °C for 20 min in the presence of 20 mol % DBU furnished the endocyclic olefins in >83:17 isomer ratios. The base-mediated isomerization of the exocyclic olefins into the endocyclic isomers was primarily driven by thermodynamic stability of the products and the effect of ring structures on deconjugation was examined.     

A novel and facile stereocontrolled synthetic method for polyhydro-quinolines and pyridopyridazines via a diene-transmissive Diels-Alder reaction involving inverse electron-demand hetero Diels-Alder cycloaddition of cross-conjugated azatrienes

Cross-conjugated azatrienes bearing an electron-withdrawing sulfonyl or benzoyl group on the nitrogen atom underwent, on heating or in the presence of a Lewis acid (TMSOTf), an initial inverse electron-demand hetero Diels-Alder reaction with electron-rich dienophiles (vinyl ether, vinyl thioether, and allenyl ether) to produce 1:1 cycloadducts with high endo selectivity. The initial cycloadducts thus obtained underwent a second Diels-Alder reaction stereoselectively on the newly formed diene unit with electron-deficient dienophiles to give the crossed bis-cycloadducts, octahydroquinolines, with high diastereo-π-facial selectivity. The N-sulfonylazatrienes tethering an ortho-cinnamyloxyphenyl dienophile at the triene terminal underwent an initial intramolecular hetero Diels-Alder reaction of the inverse electron-demand type. The subsequent second Diels-Alder reaction of the formed mono-cycloadducts completed the diene-transmissive hetero Diels-Alder protocol to give benzopyrano[3,4-c]quinolines in a highly stereoselective manner.     

Synthesis and Diels-Alder reaction of a sapphyrin derivative

Sapphyrins participate in Diels-Alder reactions with pentacene affording novel barrelene-fused sapphyrins. The new compounds were synthesized using traditional heating and microwave irradiation conditions. The experiments carried out under microwave irradiation proved cleaner, affording only the monoadduct and in higher yields.     

A tandem oximation-cyclization route to Δ-isoxazolines

3,5-Disubstituted Δ²-isoxazolines can be prepared from the corresponding β,γ-unsaturated ketones by treatment with hydroxylamine hydrochloride and sodium hydroxide. Evidence indicates that the mechanism of this reaction involves the formation of three intermediates; oximation of the ketone, rearrangement of the alkene, and intramolecular Michael addition of the resulting α,β-unsaturated oxime.     

Topologically driven tandem radical cyclization-based strategy for the synthesis of oxa- and aza-cages

Tandem radical cyclization-based strategy for the synthesis of oxa- and aza-cage compounds is described. The aryl iodides 1 and N-tosyl propargylated amine 8 lead to oxa- and aza-cages, respectively, after two tandem 5-exo-trig radical cyclizations. The alcohols 11 on reaction with ⁿBu₃SnH and AIBN give rise to the oxa-cages 14 bearing the tributyltin moiety after three tandem 5-exo-trig cyclizations. On the other hand, reaction of the propargyl ether 16 under similar conditions furnishes the oxa-cage 17 by a 5-exo-trig, 4-exo-trig, 5-exo-trig tandem radical cyclization sequence.     

Porphyrins in Diels-Alder reactions. Improvements on the synthesis of barrelene-fused chlorins using microwave irradiation

The microwave irradiation technique was applied to the Diels-Alder reaction of tetrakis(pentafluorophenyl)porphyrin with pentacene and naphthacene. Both reactions proceed within minutes to afford the corresponding monoadducts in 83% and 23% yield, respectively. When compared with the yields obtained under classical heating (22% and no reaction, respectively), this represents an impressive improvement of these reactions. Bisadducts (bacteriochlorins and isobacteriochlorins) are also obtained in the reaction with pentacene; these compounds are not formed under classical heating.     

Microwave-assisted Suzuki-Miyaura cross-coupling of 2-alkyl and 2-alkenyl-benzo-1,3,2-diazaborolanes

Nitrogen-based boronate esters, such as 2-octyl-benzo-1,3,2-diazaborolane, 2-phenethyl-benzo-1,3,2-diazaborolane, and 2-{(1E)-hexenyl}-benzo-1,3,2-diazaborolane have been shown to be suitable coupling partners with arylhalides in microwave accelerated Suzuki cross-coupling reactions. Reaction yields of up to 89% were achieved. The use of a silicon group attached to the nitrogen atom, proved to enhance the reactivity of 2-octyl-benzo-1,3,2-diazaborolane.     

Mesoporous and hexagonally ordered CuAl-SBA-15-catalyzed tandem C-C and C-O bond formation between phenols and allylic alcohols

A novel mesoporous catalyst, CuAl-SBA-15, with a hexagonally ordered porous structure prepared via a soft-templating approach in a highly acidic medium is used for tandem C-C and C-O bond formation between phenols and allylic alcohols to afford a variety of dihydrobenzopyrans in good yields. The catalyst is also found to be highly active for the synthesis of vitamin E and can be recycled several times without significant loss of its activity.     

A highly regioselective tandem 1,3-dipolar cycloaddition of cyclopropene 1,1-diesters and nitrile oxides: synthesis of highly functionalized isoxazoles

A highly regioselective tandem 1,3-dipolar cycloaddition of cyclopropene 1,1-diesters with nitrile oxides was described. This reaction supplied a new method for synthesis of polyfunctionalized isoxazole derivatives in moderate to excellent yields under mild conditions.     

Synthesis of vinylcyclopentanes via samarium(II) mediated tandem reactions

In the presence of either visible light or HMPA, SmI₂ reacts with some carbohydrate derived ω-iodoallylic alcohols, and their acetylated derivatives, to give vinylcyclopentanediol and vinylcyclopentanetriol derivatives.     

Novel three-component tandem reactions of cyclic mono ketones, isatin and sarcosine: formation of dispiropyrrolidines

One-pot, three-component tandem reactions of cyclic mono ketones, isatin and sarcosine affording dispiropyrrolidines stereoselectively are reported for the first time.