Five-membered 2,3-dioxo heterocycles: LIV. Double spiro heterocyclization of methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with 3-arylamino-5,5-dimethylcyclohex-2-en-1-ones

Methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 3-arylamino-5,5-dimethylcyclohex-2-en-1-ones in boiling benzene to give the corresponding 1,1′-diaryl-3′-benzoyl-4′-hydroxy-6,6-dimethyl-1,1′,2,4,5,5′,6,7-octahydrospiro[indole-3,2′-pyrrole]-2,4,5′-triones and 1′-aryl-4-arylamino-3-benzoyl-6′,6′-dimethyl-1′,2′,4′,5′,6′,7′-hexahydro-5H-spiro[furan-2,3′-indole]-2′,4′,5-triones whose structure was proved by X-ray analysis.     

Three-Component Spiro Heterocyclization of Pyrrolediones with Indan-1,3-dione and Acyclic Enamines

Ethyl 4,5-dioxo-2-phenyl-4,5-dihydro-1H-pynole-3-carboxylates reacted with indan-1,3-dione and 3-amino-1-phenylbut-2-en-1-one or 3-aminobut-2-enenitrile to give 3-benzoyl-2-methyl-2′,5-dioxo-5′-prienyl-1,1′,2′,5-tetrahydrospiro[indeno[1,2-b]pyridine-4,3′-pyrroles] and 2-methyl-2′,5-dioxo-5′-phenyl-1,1′,2′,5-tetrahydrospiro[indeno[1,2-b]pyridine-4,3′-pyrrole]-3-carbonitriles, respectively.

     

Cyclopropanation of 2-arylmethylidenemalononitriles,alkyl 3-aryl-2-cyanoprop-2-enoates,and N-substituted 3-aryl-2-cyanoprop-2-enamides with bromine-containing zinc enolates

Zinc enolates derived from 2,2-dibromoindan-1-one and 2,2-dibromo-1,2,3,4-tetrahydronaphthalen-1-one reacted with 2-arylmethylidenemalononitriles, alkyl 3-aryl-2-cyanoprop-2-enoates, and N-substituted 3-aryl-2-cyanoprop-2-enamides to give, respectively, 3-aryl-1′-oxo-1′,3′-dihydrospiro[cyclopropane-1,2′-indene]-2-2-dicarbonitriles, 3-aryl-1′-oxo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalene]-2,2-dicarbonitriles, alkyl 3-aryl-2-cyano-1′-oxo-1′,3′-dihydrospiro[cyclopropane-1,2′-indene]-2-carboxylates, alkyl 3-aryl-2-cyano-1′-oxo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalene]-2-carboxylates, and N-substituted 3-aryl-2-cyanol-1′-oxo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalene]-2-carboxamides as a single diastereoisomer. The stereoconfiguration of the products was determined by ¹H and ¹³C NMR spectroscopy.     

Five-membered 2.3-dioxo heterocycles: LXVIII. Three pathways in the reaction of methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates with 3-amino-5,5-dimethylcyclohex-2-en-1-one

Methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 3-amino-5,5-dimethylcyclohex-2-en-1-one having no substituent on the nitrogen atom to give 3-aroyl-4-arylamino-6′,6′-dimethyl-6′,7′-dihydro-5H-spiro[furan-2,3′-indole]-2′,4′,5′(1′H,5′H)-triones or methyl 12-aroyl-11-aryl-9-hydroxy-5,5-dimethyl-3,10-dioxo-8,11-diazatricyclo[7.2.1.0^2,7]dodec-2(7)-ene-1-carboxylates. The latter underwent thermal recyclization to 3′-aroyl-1′-aryl-4′-hydroxy-6,6-dimethyl-6,7-dihydrospiro[indole-3,2′-pyrrole]-2,4,5′(1H,1′H,5H)-triones.     

Synthesis and properties of ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-3-carboxylates

Ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates reacted with phenylhydrazine to give the corresponding hydrazones, ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1H-pyrazole-3-carboxylates, which were converted to ethyl 1′-aryl-4-formyl-5′-methyl-1-phenyl-1H,1′H-3,4′-bipyrazole-3′-carboxylates by treatment with the Vilsmeier–Haack reagent. No indole derivatives were formed from the same hydrazones under the Fischer reaction conditions, but cyclization to 2-aryl-3,4-dimethyl-6-phenyl-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-ones was observed.     

Five-membered 2,3-dioxo heterocycles: LIII. Reaction of 3-Aroyl-1<Emphasis Type="Italic">H</Emphasis>-pyrrolo[2,1-<Emphasis Type="Italic">c</Emphasis>][1,4]benzoxazine-1,2,4-triones with substituted 1,3,3-trimethyl-3,4-dihydroisoquinolines. A new approach to 13-aza analogs of steroids

3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with substituted 1,3,3-trimethyl-3,4-dihydroisoquinolines to give the corresponding 3-aroyl-4-hydroxy-1-(2-hydroxyphenyl)-5′,5′-dimethyl-5′,6′-dihydro-1H-spiro[pyrrole-2,2′-pyrrolo[2,1-a]isoquinoline]-3′,5-diones. 7′,8′-Benzo derivatives of the latter may be regarded as 13-azagonane analogs having a spiro-fused pyrrole ring at C¹⁶.     

Synthesis of new functionally substituted hetarylcarbamates from methyl {4-[(2<Emphasis Type="Italic">E</Emphasis>)-3-(4-methoxyphenyl)-prop-2-enoyl]phenyl}carbamate

Three-component condensation of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl}- carbamate with ninhydrin and L-proline in methanol–water (10: 1) afforded methyl {4-[1,3-dioxo-1′- (4-methoxyphenyl)-1,1′,2′,3,5′,6′,7′,7a′-octahydrospiro[indene-2,3′-pyrrolizin]-2′-ylcarbonyl]phenyl}carbamate. Heating of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl}carbamate with isatin and benzylamine in methanol gave methyl {4-[4′-(4-methoxyphenyl)-2-oxo-5′-phenyl-1,2-dihydrospiro[indole-3,2′-pyrrolidin]-3′-ylcarbonyl]phenyl}carbamate. The condensation of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2- enoyl]phenyl}carbamate with sarcosine and 11H-indeno[1,2-b]quinoxalin-11-one generated in situ from ninhydrin and o-phenylenediamine in boiling ethanol led to the formation of methyl {4-[4′-(4-methoxyphenyl)-1′-methyl-11,11a-dihydro-5aH-spiro[benzo[b]phenazine-6,2′-pyrrolidin]-3′-ylcarbonyl]phenyl}carbamate.     

Synthetic transformations of isoquinoline alkaloids. Synthesis of 1-halo derivatives of <Emphasis Type="Italic">endo</Emphasis>-ethenotetrahydrothebaine and their behavior in the heck reaction

Bromination of endo-ethenotetrahydrothebaine derivatives having a pyrrolidine ring fused at the C⁷-C⁸ bond, namely 1′-substituted 4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinan-2′,5′-diones, 1′-aryl-4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinans, and 4,5α-epoxy-6α,14-etheno-2′α-hydroxy-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morpphinan-5′-one, with molecular bromine in formic acid smoothly afforded the corresponding 1-bromo derivatives. Iodination of 4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]-4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]-morphinan-2′,5′-dione with iodine(I) chloride gave 4,5α-epoxy-6α,14-etheno-1-iodo-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinan-2′,5′-dione. The resulting 1-halo derivatives were brought into the Heck reaction with acrylic acid esters to obtain 1-[(E)-2-(alkoxycarbonyl)ethenyl]-substituted compounds. Demethylation of the 6-methoxy group in 1-bromo-endo-ethenotetrahydrothebaines was accomplished using boron(III) bromide in chloroform.     

Recyclization of Pyrrolediones with Arylaminoindenones. Synthesis of Indeno[1,2-<Emphasis Type="Italic">b</Emphasis>]pyridines

Dimethyl 1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2,3-dicarboxylates reacted with 3-arylamino-1H-inden-1-ones to give the corresponding methyl 1-aryl-3-[2-(arylamino)-2-oxoacetyl]-2,5-dioxo-2,5-dihydro-1H-indeno[1,2-b]pyridine-4-carboxylates.     

Reaction of methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with arylhydrazines. synthesis of isomeric 5-arylcarbamoyl-4-aroyl- and 5-aryl-4-aryloxamoyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazoles

Methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with arylhydrazines to give methyl 3-aroyl-1-aryl-2-(2-arylhydrazinyl)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylates which underwent thermal recyclization into isomeric methyl 1-aryl-5-(arylcarbamoyl)-4-aroyl-1H-pyrazole- 3-carboxylates and methyl 1,5-diaryl-4-[2-oxo-2-(arylamino)acetyl]-1H-pyrazole-3-carboxylates.     

Synthesis of spiro[imidazole-2,2′-pyrroles] by reaction of 4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with urea

Substituted alkyl 4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with urea to give alkyl 2-(carbamoylamino)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylates which underwent intramolecular cyclization to 8-hydroxy-1,3,6-triazaspiro[4.4]non-8-ene-2,4,7-triones by the action of sodium methoxide.     

Synthesis of 5,8-Diamino-Substituted Pyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]thieno[3,2-<Emphasis Type="Italic">d</Emphasis>]pyrimidines and Pyrimido[4′,5′:4,5]thieno[2,3-<Emphasis Type="Italic">c</Emphasis>]isoquinolines

Ethyl 1-amino-8,8-dimethyl-5-(piperidin-1-yl)-8,9-dihydro-6H-pyrano[4,3-d]thieno[2,3-b]pyridine-2-carboxylate and ethyl 1-amino-5-(piperidin-1-yl)-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carboxylate reacted with benzoyl isothiocyanate to give the corresponding 1-thioureido derivatives which underwent cyclization to 2,2-dimethyl-5-(piperidin-1-yl)-10-thioxo-1,4,10,11-tetrahydro-2H-pyrano[4″,3″:4′,5′]pyrido-[3′,2′:4,5]thieno[3,2-d]pyrimidin-8(9H)-one and 5-(piperidin-1-yl)-10-thioxo-1,2,3,4,10,11-hexahydropyrimido-[4′,5′:4,5]thieno[2,3-c]isoquinolin-8(9H)-one. The cyclization products were converted into 8-chloro derivatives, and the chlorine atom therein was replaced by various amines.     

Three-component condensation of methoxyarenes with isobutyraldehyde and α-substituted benzyl cyanides

Three-component condensation of anisole with isobutyraldehyde and substituted benzyl cyanides gives 1-benzyl-3,3-dimethyl-2-azaspiro[4.5]deca-6,9-dien-8-ones which undergo dienone-phenol rearrangement during the reaction. Analogous condensation of 1-methoxynaphthalene leads to the formation of 2′-benzyl-5′,5′-dimethyl-4′,5′-dihydro-4H-spiro[naphthalene-1,3′-pyrrol]-4-ones.     

An efficient synthesis of 1′,4′-dihydro-2′<Emphasis Type="Italic">H</Emphasis>-spiro[azetidin-2,3′-quinolin]-2′-one

A facile synthesis of 1′,4′-dihydro-2′H-spiro[azetidin-2,3′-quinolin]-2′-one is described. Synthetic highlights include simultaneous construction of azetidine ring by intramolecular alkylation and formation of spirocarbon center in excellent yield plus removal of p-methoxybenzyl (PMB) amide protective group in mild condition with good yield.     

Thermolysis of 1-(methylideneamino)-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2,3-diones. Synthesis of pyrazolooxazines by [4 + 2]-cycloaddition of azomethine imines to alkenes

Thermolysis of methyl 3-acyl-1-[(diphenylmethylidene)amino]-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates generates 4-acyl-1-(diphenylmethylidene)-3-(methoxycarbonyl)-1H-pyrazol-1-ium-5-olates which react with alkenes to give methyl 3-acyl-7,7-diphenyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2- carboxylates. The product structure was confirmed by X-ray analysis.     

Five-membered 2,3-dioxo heterocycles: LI. Reaction of 3-aroyl-2,4-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones with 3-amino-5,5-dimethylcyclohex-2-en-1-ones

3-Aroyl-2,4-dihydro-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones react with N-unsubstituted and N-substituted 3-amino-5,5-dimethylcyclohex-2-en-1-ones to give 3′-aroyl-4′-hydroxy-1′-(o-hydroxy-phenyl)-6,6-dimethyl-6,7-dihydrospiro[indole-3,2′-pyrrole]-2,4,5′(1H,1′H,5H)-triones. The molecular and crystalline structure of the 1-cyclohexyl-substituted derivative was studied by X-ray analysis.     

Synthesis and transformations of 3-allyl-7,10-dimethyl-2-sulfanylidene-2,3,5,6-tetrahydrospiro[benzo[<Emphasis Type="Italic">h</Emphasis>]quinazoline-5,1′-cyclopentan]-4(1<Emphasis Type="Italic">H</Emphasis>)-one

Ethyl 4′-amino-5′,8′-dimethyl-1′H-spiro[cyclopentane-1,2′-naphthalene]-3′-carboxylate reacted with allyl isothiocyanate to give 3-allyl-7,10-dimethyl-2-sulfanylidene-2,3,5,6-tetrahydrospiro[benzo[h]quinazoline- 5,1′-cyclopentan]-4(1H)-one. Reactions of the latter with alkyl halides and hydrazine hydrate and subsequent transformations of the products afforded a series of new benzo[h]quinazoline derivatives containing an allyl group in the 3-position.     

Five-membered 2,3-dioxo heterocycles: LXX. Spiro heterocyclization of 1H-pyrrole-2,3-diones by the action of 1,5-binucleophiles. Crystalline and molecular structure of ethyl 1′-benzyl-7-methoxy-3,3-dimethyl-1,2′-dioxo-5′-phenyl-1′,2,2′,3,4,10-hexahydro-1H-spiro[acridine-9,3′-pyrrole]-4′-carboxylate

Ethyl 1-alkyl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates reacted with 3-arylamino-5,5-dimethylcyclohex-2-en-1-ones as carbon-centered 1,5-binucleophiles to give the corresponding substituted ethyl 1′-alkyl-3,3-dimethyl-1,2′-dioxo-5′-phenyl-1′,2,2′,3,4,10-hexahydro-1H-spiro[acridine-9,3′-pyrrole]-4′-carboxylates whose structure was proved by X-ray analysis.     

Three-component condensation of 3-aminothiophene derivatives with isatines and Meldrum’s acid. Synthesis of 2,5′-dioxo-3′-phenyl-5′,6′-dihydro-4′H-spiro[indoline-3,7′-thieno[3,2-b]pyridine]-2′-carboxylic acids

A method for the synthesis of 2,5′-dioxo-3′-phenyl-5′,6′-dihydro-4′H-spiro[indoline-3,7′-thieno[3,2-b]pyridine]-2′-carboxylic acids was elaborated based on the three-component condensation of 3-aminothiophenes, Meldrum’s acid, and isatines.     

Reactions of 3-Aroylpyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinoxaline-1,2,4(5<Emphasis Type="Italic">H</Emphasis>)-triones with 2,3-Dihydrofuran and 3,4-Dihydro-2<Emphasis Type="Italic">H</Emphasis>-pyran

3-Aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones reacted with 2,3-dihydrofuran and 3,4-dihydro-2H-pyran to give mixtures of the corresponding hetero-Diels–Alder (furo- and pyrano[3″,2″: 5′,6′]pyrano- [4′,3′: 2,3]pyrrolo[1,2-a]quinoxalines) and Michael adducts (furyl- and pyranylpyrrolo[1,2-a]quinoxalines).