Investigation of regioselectivity in the synthesis of spiro [pyrrolidine-2,3′-oxindoles] by use of the Huisgen reaction

The Huisgen reaction has been used to synthesize five-membered heterocyclic compounds in high yield and with high regio and stereoselectivity. In the synthesis of spiro [pyrrolidine-2,3′-oxindole] derivatives from isatin, α-amino acids, and (E)-β-phenyl nitroolefins, two regioisomers were obtained in each reaction. The regioselectivity of the major product was found to be different from that in reported work, and was investigated at the B3LYP/6-311G* level of theory. On the basis of this new finding, several conditions, for example molar ratio, solvent, and temperature, which affect the regioselectivity of this reaction were investigated; the results obtained are discussed. It was found that the regioselectivity of this reaction was affected by solvent and temperature, irrespective of the ratio of the reactants. Low temperature and high solvent polarity leads to high regioselectivity, and protic solvents result in higher yield and regioselectivity. These results are of benefit for regioselective synthesis of some compounds.     

Stereoselective synthesis of spiro[pyrrolidin-3,3′-oxindoles] via organocatalyzed asymmetric Mannich-type reaction

The organocatalyzed asymmetric Mannich-type spirocyclization was employed to access the spiro[pyrrolidin-3,3′-oxindoles], a biologically privileged ring structure, from readily available 2-oxotryptaphan methyl ester and aromatic aldehydes. The stereoselectivity of this cyclization are closely correlated with the organocatalyst and solvent used for the reaction. The best diastereoselectivity (d.r. ≥99%) was achieved using only 5% loading of the bifunctional organocatalyst, Takemoto’s thiourea, and dioxane as solvent, resulting in the formation of the the spirocycle with the (2′R, 3R) configuration. The yield could be increased up to 97% when excess of benzaldehyde was used to overcome its trimerization.     

Synthesis of new heterocyclic systems—substituted spiro[chromene-4,3′-indoles] and spiro[indole-3,4′-quinolines]

Methods have been developed for the synthesis of new heterocyclic systems, spiro[chromene-4,3′- indoles] and spiro[indole-3,4′-quinolines] by the base-catalyzed domino reaction of isatins with 5,5-dimethylcyclohexane- 1,3-dione (or 5,5-dimethyl-3-anilinocyclohex-2-en-1-one) and ethyl cyanoacetate.     

Synthesis of spiro[furo[3,4-b]pyran-4,3′-pyrroles] by reaction of pyrrolediones with malononitrile and tetronic acid

Russian Journal of Organic Chemistry - Substituted ethyl...     

Highly diastereoselective synthesis of spiro[tetrahydrothiophene-3,3′-pyrazol] with an all-carbon quaternary stereocenter via [3 + 2] cascade Michael/Michael cyclization catalyzed by DABCO

The diastereoselective formation of spiro[tetrahydro thiophene-3,3′-pyrazol] derivatives has been achieved via a Michael/Michael cyclization reaction. The reaction was performed using trans-ethyl 4-mercapto-2-butenoate 1 with various 4-benzylidene-5-methyl-2-phenylpyrazolones 2 catalyzed by 1,4-diazabicyclo[2.2.2]octane (DABCO) in toluene at 0 °C. The reaction proceeds rapidly and affords the corresponding spiro[tetrahydrothiophene-3,3′-pyrazol] derivatives in excellent yields and moderate to excellent diastereoselectivities (up to 98% yield and >20:1 dr).     

Construction of indolenine-substituted spiro[pyrrolidine-2,3′-oxindoles] from 2-alkenylindolenines and isatin-derived azomethine ylides

An organic base-catalyzed 1,3-dipolar cycloaddition between 2-alkenylindolenines and azomethine ylides derived from isatins and benzylamines was successfully developed to assemble indolenine-substituted spiro [pyrrolidine-2,3′-oxindole] ring systems. Generally, good regioselectivities (up to 14:1 rr) and high yields (up to 91%) were obtained under mild conditions.     

New multicomponent domino reaction on water: highly diastereoselective synthesis of spiro[indoline-3,4′-pyrazolo[3,4-b]pyridines] catalyzed by NaCl

A direct and efficient approach for the preparation of medicinally promising pyrazolopyridinyl spirooxindoles has been developed through a sequential one-pot, three-component reaction of easily available isatin, α-cyanoacetic ester or malononitrile, and 5-amino-3-methylpyrazole catalyzed by sodium chloride in water. Desired products were obtained in high to excellent yields using a simple workup procedure. The product synthesized using α-cyanoacetic ester showed high diastereoselectivity in which the stereochemistry of major diastereomer was confirmed by X-ray diffraction analysis. The present green synthesis shows attractive characteristics such as the use of water as the reaction medium, one pot conditions, short reaction period, easy workup/purification, and reduced waste production, without use of any acid or metal promoters.     

A new rearrangement of spiro[indane-1,3′-thiophene] and spiro[naphthalene-1,3′-thiophene] derivatives accompanied by opening of the cycloalkane ring

Abstract  

The new thioamides 2-oxoindane-1-carbothioamides and 2-oxo-1,2,3,4-tetrahydronaphthalene-1-carbothioamides underwent conjugated addition to (E)-β-nitrostyrenes followed by cyclization to give products containing 5-hydroxyimino-2-aryliminothiophene rings spiro-annulated to the 2-indanone or 2-tetralone system. On treatment with hydrochloric acid in boiling methanol the compounds underwent a new rearrangement, involving transformation of the 2-aryliminothiophene ring to a pyrrole and an opening of the alicyclic ring in the proximity of the carbonyl group, affording 2-(1,3-diaryl-2-oxo-5-thioxopyrrol-4-yl)benzeneacetic or 2-(1,3-diaryl-2-oxo-5-thioxopyrrol-4-yl)benzenepropanoic acid methyl esters. The structures of two selected pyrrole derivatives were determined by X-ray crystal analyses. The thioamides derived from 2-indanone showed unexpected reactivity towards primary alcohols and underwent conversion to 2-hydroxy-1H-indene-3-thiocarboxylic acid O-esters.     

Recyclization of spiro[3a-Hydroxypiperidin-4,2′-oxiranes] in basic medium

It is shown that heating spiro[3a-hydroxypiperidin-4,2-oxiranes] in aqueous base gives rearrangement into derivatives of 3,4-epoxypiperidines. The structures of the latter were confirmed by spectral data and by chemical informations.Belorussian State Technological University, Minsk 220030. Translated from Khimiya Geterotsiklicheskikh Soedineii, No. 9, pp. 1213–1215, September, 1994. Original article submitted July 29, 1994.     

Highly efficient and green synthesis of spiro[indoline-3,9′-xanthene]trione and spiro[chromene-4,3′-indoline]-3-carbonitrile derivatives in water catalyzed by graphene oxide-supported dicationic ionic liquid

Research on Chemical Intermediates - In this article, a mild and highly efficacious synthetic route has been developed for the synthesis of spiro[indoline-3,9′-xanthene]trione and...     

One-pot,three-component synthesis of spiro[indeno[1,2-b]quinoline-10,3′-pyrroles] via the Hantzsch-type reaction of 1H-pyrrole-2,3-diones

A new methodology for the synthesis of spiro[indeno[1,2-b]quinoline-10,3′-pyrrole] derivatives via a Hantzsch-type reaction has been developed. This process involves the one-pot, three-component reaction of a 1H-pyrrole-2,3-dione, an aminocyclohexenone and 1,3-indanedione in acetic acid at reflux. Operationally simple, metal-free reaction conditions, simplicity of product isolation and good yields are key advantages of this methodology.     

Combination of the Claisen-Schmidt reaction,the Michael addition,and the Hantzsch reaction in the synthesis of 2,6′-bis-aryl-3,4′-bipyridines

Russian Chemical Bulletin - Pyridine-3-carbaldehyde reacted with 1-(aryl)ethan-1-ones to give 1,5-diaryl-3-(pyridin-3-yl)pentane-1,5-diones, which were further converted to...     

Synthesis of spiro[indole-3,3′-[1,3,4]thiadiazino[3,2-a]benzimidazoles] and spiro[indole-3,6′-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines]

A method for annulation of the tetrahydrothiadiazine ring to benzimidazoles and 1,2,4-tri-azoles was developed. A number of earlier unknown [1,3,4]thiadiazino[3,2-a]benzimidazoles and triazolo[3,4-b][1,3,4]thiadiazines were obtained as spiro compounds with the oxindole fragment. According to NMR and X-ray diffraction data, the formation of the tetrahydrothiadiazine ring is a diastereospecific process.     

Synthesis of Spiro[benzo[h]chromene-4,3′-indoles] and Spiro[benzo[f]chromene-1,3′-indoles]

Russian Journal of Organic Chemistry - New spiro heterocycles, spiro[benzo[h]chromene-4,3′-indoles] and spiro[benzo[f]chromene-1,3′-indoles], have been synthesized in 50–60% yield...     

Comparison of the electronic absorption spectra of the isomeric 1,1′- and 2,2′-binaphthyl spiro [cyclophosphazene] derivatives

It has been found that the u.v.-spectrum of the monospiro [(2,2′-dioxybinaphthyl-1,1′) cyclophosphazene] (3) closely resembles those of the other previously described 7-membered 2,2′-bridged 1,1′-binaphthyl derivatives. An hitherto unreported effect of the associated influence of α-substitution, β-coupling and the next cyclization on the u.v. absorption of naphthalene chromophore has been shown by the comparison of the electronic spectra of 1-naphthol (5), 1,1′-dihydroxybinaphthyl-2,2′ (6) and monospiro [(1,1′-dioxybinaphthyl-2,2′) cyclophosphazene] (7). Exclusively strong resonance interaction between the conjugated naphthalene rings was evidenced for 7.     

Synthesis of spiro[isoquinoline-4,4′-pyran]-3-imines

A method has been developed for the synthesis of 4-[2-(bromomethyl)phenyl] tetrahydro-2H-4-pyrancarbonitrile and a study was carried out on the reaction of this compound with primary amines, which, depending on the conditions, leads to either 4-[2-(R-aminomethyl)phenyl]tetrahydro-2H-4-pyrancarbonitriles or hydrobromides of 2-R-aryl-2,3,2,3,5,6-hexahydrospiro[isoquinoline-4(1H),4-pyran]-3-imines.Taras Shevchenko Kiev University, 252017 Kiev, Ukraine; e-mail: vkysil@mail.univ.kiev.ua. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1035–1041, August, 2000.     

Synthesis of spiro[furan-3,3′-indolin]-2′-ones by PET-catalyzed [3+2] reactions of spiro[indoline-3,2′-oxiran]-2-ones with electron-rich olefins

An efficient procedure for the synthesis of spiro[furan-3,3′-indolin]-2-ones and dispiro[cycloalkane-1,2′-furan-3′,3″-indolin]-2″-ones has been achieved in high yields and stereoselectivity by photoinduced electron transfer-catalyzed [3+2] reactions of substituted spiro[indoline-3,2′-oxiran]-2-ones with olefins. The reactions proceed by ring opening of spiro[indoline-3,2′-oxiran]-2-ones via C_β–O bond cleavage and subsequent cycloaddition with olefins by using 2,4,6-triphenylpyrylium tetarfluoroborate (TPT) as a sensitizer.     

Engaging thieno[2,3-b]indole-2,3-dione for the efficient synthesis of spiro[indoline-3,4′-thiopyrano[2,3-b]indole] by reaction with N-substituted isatilidenes

A simple and efficient method, proceeding through a new mechanistic pathway, for the synthesis of spiro[indoline-3,4-thiopyrano[2.3-b]indole derivatives have been developed by exploiting the reaction of thieno[2,3-b]indole-2,3-dione with N-substituted isatilidenes. The compounds synthesized have been screened for antibacterial activity. The generality of the reaction and mechanistic rationale are presented.