Synthesis of 3,3′-disubstituted-2,2′-biindolyls through sequential palladium-catalysed reactions of 2,2,2-trifluoro-N-(2-(4-[2,2,2-trifluoro-acetylamino)-phenyl]-buta-1,3-diynyl)-phenyl)-acetamide with organic halides/triflates

Palladium-catalysed reactions of aryl iodides/vinyl triflates with 2,2,2-trifluoro-N-(2-(4-[2,2,2-trifluoro-acetylamino)-phenyl]-buta-1,3-diynyl)-phenyl)-acetamide provide a straightforward entry into 3,3′-disubstituted-2,2′-biindolyls. Subsequent application of the procedure to homochiral aryl iodides affords the corresponding chiral 3,3′-disubstituted-2,2′-biindolyls. The methodology can also be applied to the synthesis of benzo[c]indolo[2,3-a]carbazoles.     

Iron-catalyzed oxidative homo-coupling of indoles via C-H cleavage

A new method for the homo-coupling of indoles has been developed by the use of FeCl₃ as catalyst and molecular oxygen as the only oxidant. The protocol provides a practical and straightforward approach toward 3,3′-biindolyls.     

The preparation of substituted bithiophenyl aldehydes via the ring opening of dithieno[2,3-b:3′,2′-d]thiophene in the presence of n-BuLi

In the presence of n-BuLi in THF at low temperature, the phenomena of ring opening of symmetric substituted dithieno[2,3-b:3′,2′-d]thiophenes were observed. After quenching the organolithium intermediates with dry DMF, a series of substituted novel bithiophenyl aldehydes were prepared in good to excellent yields. The mechanism shows the key step for the ring opening of dithieno[2,3-b:3′,2′-d]thiophene is the nucleophilic attack of butyl anion onto the sulfur atom of the central ring. Total ten samples of symmetric substituted dithieno[2,3-b:3′,2′-d]thiophenes and their ring-opened products, the substituted bithiophenyl aldehydes were characterized by ¹H NMR, ¹³C NMR, and HRMS. Two ring-opened products were confirmed by X-ray single crystal analysis.     

Cascade assembly of N,N′-dialkylbarbituric acids and aldehydes: a simple and efficient one-pot approach to the substituted 1,5-dihydro-2H,2′H-spiro(furo[2,3-d]pyrimidine-6,5′-pyrimidine)-2,2′,4,4′,6′(1′H,3H,3′H)-pentone framework

Cascade assembly of N,N′-dialkylbarbituric acids and aldehydes in the presence of bromine leads to the selective and efficient formation of substituted 1,5-dihydro-2H,2′H-spiro(furo[2,3-d]pyrimidine-6,5′-pyrimidine)-2,2′,4,4′,6′-(1′H,3H,3′H)-pentones in 70-88% yields via a complex cascade process. Spirobarbiturates containing the furo[2,3-d]pyrimidine framework are a class of compounds with interesting pharmacological and physiological activity.     

Intramolecular arylation reactions: first efficient synthesis of novel fused pyridoimidazoquinolinones or pyridoimidazoazepinones libraries

An efficient method for the synthesis of new polycyclic skeletons: pyrido[2′,1′:2,3]imidazo[5,4-c]quinolin-6(5H)-ones and pyrido[2′,1′:2,3]imidazo[5,4-c]azepin-7(6H)-ones libraries is described via Pd-catalyzed intramolecular arylation involving C(sp2)-H activation. This method permits the synthesis of polycyclic derivatives in good yield. The process tolerates a variety of aryl substituents as well as alkyl imidazo[1,2-a]pyridine-2-carboxamide structures. The resultant compounds, 10(11)-chloro-pyrido[2′,1′:2,3]imidazo[5,4-c]quinolinones or azepinones are functionalized under Suzuki cross-coupling conditions to give polyfunctional compounds.     

Domino reactions in water for the stereoselective synthesis of novel spiro dihydro-2′H-[indene-2,3′-thiophen]-1(3H)-ones with three contiguous stereocenters

The domino reactions of (E)-2-(aryl)-2,3-dihydro-1H-inden-1-ones and 1,4-dithiane-2,5-diol in the presence of triethylamine in water stereoselectively afforded a library of 2′-(aryl)-4′-hydroxy-4′,5′-dihydro-2′H-spiro[indene-2,3′-thiophen]-1(3H)-ones. This transformation presumably proceeds via the generation of 2-mercaptoacetaldehyde from 1,4-dithiane-2,5-diol followed by Michael addition–intramolecular aldol sequence with C–C and C–S bond formations and creation of three contiguous stereocenters in a one-pot operation.     

Synthesis of new compounds containing the 2,3-dihydro[1,4]dioxino[2,3-b]pyridine heterocyclic system as a substructure

2,3-Dihydro-spiro[1,4]dioxino[2,3-b]pyridine-3,3′-pyrrolidine (8A) and 2,3-dihydro-spiro[1,4]dioxino[2,3-b]pyridine-3,4′-piperidine (9A) have been synthesized from 2-chloro-3-pyridinol. The corresponding 2,3′ (8B) and 2,4′ (9B) isomers were obtained via the Smiles rearrangement, while 9B was also selectively synthesized from 2-nitro-3-pyridinol. The separation of the isomers A and B under the sulfamide form was carried out by flash column chromatography. Subsequent transformations of the corresponding dioxinopyridine derivatives were described.     

A novel and efficient one-pot synthesis of furo[3′,4′:5,6]pyrido[2,3-c]pyrazole derivatives using organocatalysts

A novel approach to one-pot synthesis of dihydrofuro[3′,4′:5,6]pyrido[2,3-c]pyrazole and indeno[2′,1′:5,6]pyrido[2,3-c]pyrazole derivatives have been investigated using organocatalysts that are recyclable. This new protocol has the advantages of environmental friendliness, higher yield, low cost, as well as convenient operation. The catalytic efficiency of various small organocatalysts such as l-proline, trans-4-hydroxy-l-proline, l-thiaproline, cinchonidine, (+)-cinchonine, and dl-2-phenylglycine has also been studied.     

Benzo[b]thiophene as a template for substituted quinolines and tetrahydroquinolines

An original methodology starting from 3-aroyl-2-(2′-nitro-4′-methoxyphenyl)-benzo[b]thiophene allows the synthesis of unusual fused heterocycles. Direct hydrogenation with nickel catalysts followed by desulfurisation led to 2,3-diarylquinolines or 2,3-diaryltetrahydroquinolines.     

Synthesis of 1′,3,3′,4-tetrahydrospiro[chromene-2,2′-indoles] as a new class of ultrafast light-driven molecular switch

A new class of ultrafast light-driven molecular switch has been designed and synthesized. The reaction of 1-substituted 2-methylidene-3,3-dimethyl-2,3-dihydro-1H-indoles with 2-chloromethyl-4-nitrophenol afforded 1′,3,3′,4-tetrahydrospiro[chromene-2,2′-indoles], following a basic workup. The spectroscopic properties and nanosecond-resolved photoinduced dynamics of five compounds in the 1′,3,3′,4-tetrahydrospiro[chromene-2,2′-indole] family were investigated.     

Novel fluoro-substituted benzo- and benzothieno fused pyrano[2,3-c]pyrazol-4(1H)-ones

A straightforward, two-step synthesis of fluoro substituted chromeno[2,3-c]pyrazol- and [1]benzothieno[2′,3′:5,6]pyrano[2,3-c]pyrazol-4(1H)-ones, respectively, is presented. Hence, treatment of 1-substituted or 1,3-disubstituted 2-pyrazolin-5-ones with fluoro substituted 2-fluorobenzoyl chlorides or 3-chloro-6-fluoro-1-benzothiophene-2-carbonyl chloride using calcium hydroxide in refluxing 1,4-dioxane gave the corresponding 4-aroylpyrazol-5-ols, which were cyclized into the fused ring systems. 5-Fluorochromeno[2,3-c]pyrazol-4(1H)-one was obtained upon treatment of the 1-(4-methoxybenzyl) protected congener with trifluoroacetic acid. Treatment of 5-fluorochromeno[2,3-c]pyrazol-4(1H)-ones with methylhydrazine afforded novel tetracyclic ring systems such as 2-methyl-7-phenyl-2,7-dihydropyrazolo[4′,3′:5,6]pyrano[4,3,2-cd]indazole. Detailed NMR spectroscopic investigations (¹H, ¹³C, ¹⁵N, ¹⁹F) with the obtained compounds were undertaken.     

Selective synthesis of Neu5Ac2en and its oxazoline derivative using BF3·Et2O

Application of the Lewis acid BF₃·Et₂O to the selective synthesis of 5-acetamido-2,6-anhydro-3,5-dideoxy-d-glycero-d-galacto-non-2-enonic acid (Neu5Ac2en) and the related oxazoline, methyl 7,8,9-tri-O-acetyl-2,3,4,5-tetradeoxy-2,3-didehydro-2,3-trideoxy-4′,5′-dihydro-2′-methyloxazolo[5,4-d]- d-glycero-d-talo-non-2-enonate is described.     

Novel peripherally functionalized seco-porphyrazines: synthesis, characterization and spectroscopic evaluation

Co-macrocyclizations of 2,3-dipropylmaleonitrile and 2,3-di-(4-(methoxycarbonyl)phenyl)maleonitrile, respectively, with N,N′-dibenzyl-N,N′-di-(11-tetrahydropyranyloxy-3,6,9-trioxo-undecyl))maleonitrile and N,N,N′,N′-tetramethylmaleonitrile were used to prepare derivatives of the 4,5-diamino-porphyrazine systems including the zinc(II) complexes. Subsequent oxidation of the macrocycles with potassium permanganate gave the corresponding seco-porphyrazines. These were shown to be efficient sensitizers for the production of singlet oxygen (Φ_Δ=0.15-0.57) by the determination of their photophysical properties.     

Substituted chromones in [3+2] cycloadditions with nonstabilized azomethine ylides: synthesis of 1-benzopyrano[2,3-c]pyrrolidines and 1-benzopyrano[2,3-c:3,4-c′]dipyrrolidines

Chromones bearing electron-withdrawing substituents at the 2- or 3-position react with nonstabilized azomethine ylides to produce 1-benzopyrano[2,3-c]pyrrolidines in good yields. Reactions of 3-cyanochromones proceed diastereoselectively to give 1-benzopyrano[2,3-c]pyrrolidines and tetrahydro-1H-spiro[chromeno[2,3-c]pyrrol-9,5′-oxazolidine]-9a-carbonitriles, depending on the reactant ratio, as a result of a 1,3-dipolar cycloaddition of the azomethine ylide at the double bond and carbonyl group of the chromone system. The latter undergoes demethylenation and recyclization into a novel hexahydrochromeno[2,3-c:3,4-c′]dipyrrole tetracyclic system on heating with hydrochloric acid.     

3-Cyanochromones in [3+2] cycloadditions with an azomethine ylide derived from sarcosine and formaldehyde. A short synthesis of 1-benzopyrano[2,3-c:3,4-c′]dipyrrolidines

Reactions of 3-cyanochromones with sarcosine and paraformaldehyde proceed diastereoselectively to give 1-benzopyrano[2,3-c]pyrrolidines and tetrahydro-1H-spiro[chromeno[2,3-c]pyrrol-9,5′-oxazolidine]-9a-carbonitriles, depending on the reactant ratio, as a result of a 1,3-dipolar cycloaddition of the intermediate nonstabilized azomethine ylide at the double bond and carbonyl group of the chromone system. The latter undergoes demethylenation and recyclization into a novel hexahydrochromeno[2,3-c:3,4-c′]dipyrrole tetracyclic system on heating with hydrochloric acid.     

Spirooxindoles: reaction of 2,6-diaminopyrimidin-4(3H)-one and isatins

A simple and efficient cyclocondensation reaction of 2,6-diaminopyrimidin-4(3H)-one and isatins for the synthesis of spiro[pyrimido[4,5-b]quinoline-5,5′-pyrrolo[2,3-d]pyrimidine] and spiro[indoline-pyrido[2,3-d:6,5-d′]dipyrimidine] derivatives is reported.     

Intramolecular 4+2 cycloaddition of thieno[2,3-e][1,2,4]triazines: routes towards condensed thieno[2,3-b]pyridines

Synthetic approaches towards new condensed thienopyridine ring systems including furo[2,3-b]thieno[3,2-e]pyridines, bisthieno[2,3-b:3′,2′-e]pyridines, 5H-chromeno[2,3-b]thieno[3,2-e]pyridines, 5H-benzo(f)chromeno[2,3-b]thieno[3,2-e]pyridines have been achieved by application of intramolecular 4+2 cycloaddition reactions of suitably designed thieno[2,3-e][1,2,4]triazines tethered with alkene or alkyne terminals.     

Application of 3,3′-disubstituted xylBINAP derivatives in inter- and intramolecular asymmetric Heck/Mizoroki reactions

3,3′-Disubstituted xylBINAP derivatives were applied to inter- and intramolecular asymmetric Heck/Mizoroki reactions. The results from these reactions were compared to those obtained with (R)-xylBINAP, (S)-BINAP and 3,3′-disubstituted BINAP derivatives. Catalysts derived from 3,3′-disubstituted xylBINAP ligands were found to be most effective in the arylation of 2,3-dihydrofuran in terms of reaction times, conversions, and product enantioselectivity.     

A novel one-pot and efficient procedure for the synthesis of 3H-spiro[isobenzofuran-1,6′-pyrrolo[2,3-d]pyrimidine]-2′,3,4′,5′-tetraones

A novel and practical one-pot procedure is described for the preparation of several new of 3H-spiro[isobenzofuran-1,6′-pyrrolo[2,3-d]pyrimidine]-2′,3,4′,5′-tetraones based on the addition reaction of ninhydrin and 6-aminouracils followed by oxidative cleavage of their corresponding dihydroxyindenopyrrolopyrimidines.     

A new route to the versatile synthesis of thiopyrano[2,3-b:6,5-b′]diindoles via 2-(alkylthio)-indole-3-carbaldehydes

A versatile synthesis of symmetrically and unsymmetrically substituted thiopyrano[2,3-b:6,5-b′]diindoles has been developed by the condensation of 2-(alkylthio)-indole-3-carbaldehydes with indoline-2-thiones in the presence of catalytic amount of ethylenediamine diacetate (EDDA). The EDDA mediated condensation leads to a spontaneous cyclization followed by aromatization to form thiopyrano[2,3-b:6,5-b′]diindoles in quantitative yields.