1,7-Electrocyclization reactions of stabilized α,β:γ,δ-unsaturated azomethine ylides

Stabilized α,β:γ,δ-unsaturated azomethine ylides were generated by the deprotonation of isoquinolinium salts. 1,7-Electrocyclization of these dipoles, followed by a 1,5-hydrogen shift, gives tetrahydro[5,6]azepino[2,1-a]isoquinolines.     

1,7-Electrocyclisations of stabilised azomethine ylides

Ester-stabilised α,β:γ,δ-unsaturated azomethine ylides 9 were generated by the deprotonation method from isoquinolinium salts 8. 1,7-Electrocyclisation of these dipoles followed by a 1,5-hydrogen shift, gives tetrahydro[5,6]azepino[2,1-a]isoquinolines 10.     

Interactions between Oxygen Lone-Pair Orbitals and Double-Bond π-Orbitals in β,γ-Unsaturated,Bicyclic Ketones; a PE-Spectroscopic Investigation

The HE(Iα) photoelectron (PE) spectra of 2,3,5,6-tetramethylidene-2-bicyclo[2.2.1]heptanone ( 12 ), 5,6-dimethylidene-2-bicyclo[2.2.1]heptanone ( 14 ), 5,6-dimethylidene-2-bicyclo[2.2.2]octanone ( 16 ), and 5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanone ( 17 ) have been recorded, Comparison with the PE data of other β,γ-unsaturated ketones and parent alkenes, and with the result of ab initio STO-3G calculations, confirm the existence of significant interactions between the oxygen lone-pair orbital n_o and the double-bond π orbital(s). It is argued that the major contributions to the basis energy shifts and to the cross term between the n_o and π orbitals are due to a ‘through-bond’ mechanism.     

Benzimidazole derivatives with zwitterion structures

2-Pyridinium and β- and γ-picolinium-5,6-dinitrobenzimidazole betaines were obtained by reaction of 5,6-dinitro-2-chlorobenzimidazole with pyridine and β- and γ-picolines.     

Synthesis of new Di-, Tetra-, and hexahydropyrazolo[3,4-e][1,4]diazepine derivatives

Alkaline hydrolysis of 5-(2,2-diethoxyethyl-, aroylmethyl-, or ethoxycarbonylmethyl)-1H-pyrazolo-[3,4-e]pyrimidin-4(5H)-ones gave 5-amino-N-(2,2-diethoxyethyl-, aroylmethyl-, or carboxymethyl)-1H-pyrazole-4-carboxamides which underwent cyclization to the corresponding 7-hydroxy-5,6,7,8-tetrahydropyrazolo-[3,4-e][1,4]diazepin-4(1H)-ones, 5,6-dihydropyrazolo[3,4-e][1,4]diazepin-4(1H)-ones, and 1,5,6,8-tetrahydropyrazolo[3,4-e][1,4]diazepine-4,7-diones. Reduction of the cyclization products with NaBH4 and LiAlH4 afforded 5,6,7,8-tetrahydropyrazolo[3,4-e][1,4]diazepin-4(1H)-ones and 1,4,5,6,7,8-hexahydropyrazolo[3,4-e]-[1,4]diazepines.     

Practical synthesis of 3-bromo-5,6-dihydropyridin-2-ones via β,γ-unsaturated α-bromo-ketene/imine cycloaddition

An approach to 3-bromo-4-alkyl-6-aryl-5,6-dihydropyridin-2-ones and 3-bromo-5-ethyl-6-aryl-5,6-dihydropyridin-2-ones starting from β,γ-unsaturated α-bromoketenes and imines is reported. The presence of a bromine atom on the double bond allows performing aziridination or bromine displacement with an amine. The reaction gave fused bicyclic N-allyl-aziridines or 3-amino-substituted 5,6-dihydropyridin-2-ones, depending on the substituents on the six-membered ring.     

Pyrimido[4,5-f]quinazolines

The corresponding 6-dimethylaminomethylen-5-oxo-5,6,7,8-tetrahydroquinazolines were obtained from reactions of 2-substituted and 2,7-disubstituted 5-oxo-5,6,7,8-tetrahydroquinazolines with the dimethylacetal of DMF. Sixteen 2,8-disubstituted 5,6-dihydropyrimido[4,5-f]quinazolines were obtained from the reaction of 2-phenyl- and 6-(dimethylamino)methylen-5-oxo-2-(4-pyridyl)-5,6,7,8-tetrahydroquinazolines with guanidine and eight amidines. The corresponding 6-hydroxymethylene derivative was obtained by hydrolysis of 6-(dimethylamino)methylen-5-oxo-1-phenyl-5,6,7,8-tetrahydroquinazoline.     

From chiral and prochiral N-allylpyrroles to stereodefined pyrrole fused architectures: A particular application of the rhodium-catalyzed hydroformylation

We review our recent results on the rhodium-catalyzed hydroformylation of chiral and prochiral N-allylpyrroles as a synthetic route to stereodefined 5,6-dihydro- and 5,6,7,8-tetrahydroindolizines. The indolizine nucleus at different degrees of unsaturation is a building block of natural and synthetic target compounds; thus new approaches, especially if stereoselective and/or stereospecific, are highly desirable. The construction of the indolizine architectures reported here occurs by formation of a C8-C9 bond through intramolecular cyclization of the 4-pyrrolylbutanal intermediate.     

A tandem multi-component synthesis of 5,7-diaryl-5,6,7,8-tetrahydro-1H-pyrido[3,4-b][1,4]thiazin-2(3H)-ones

The five-component reaction of ethyl 2-[(2-oxopropyl)sulfanyl]acetate, aromatic aldehydes, and ammonium acetate affords two diastereomers of 5,7-diaryl-5,6,7,8-tetrahydro-1H-pyrido[3,4-b][1,4]thiazin-2(3H)-ones via a novel tandem Mannich-enamine-substitution sequence. Presumably, they are generated from ethyl 2-[(4-oxo-2,6-diaryl-3-piperidinyl)sulfanyl]acetates. During the formation of the trans-5,7-diaryl-5,6,7,8-tetrahydro-1H-pyrido[3,4-b][1,4]-thiazin-2(3H)-ones from ethyl 2-[(4-oxo-2,6-diaryl-3-piperidinyl)sulfanyl]acetates, the configuration at the carbon bearing an aryl group adjacent to the enamide CC double bond is inverted via ring opening and closure. When o-substituted benzaldehydes were employed in this reaction, 5,7-diaryl-5,6-dihydro-1H-pyrido[3,4-b][1,4]thiazin-2(3H)-ones were obtained via air oxidation, along with trans-5,7-diaryl-5,6,7,8-tetrahydro-1H-pyrido[3,4-b][1,4]-thiazin-2(3H)-ones.     

Reactions of 5,6,7,8-Tetrafluoro-4-hydroxy-2H-chromen-2-ones with methylamine

5,6,7,8-Tetrafluoro-4-hydroxy-2H-chromen-2-one reacts with methylamine to give methylammonium 5,6,7,8-tetrafluoro-2-oxo-2H-chromen-4-olate, regardless of the solvent. The reaction of 3-acetyl-5,6,7,8-tetrafluoro-4-hydroxy-2H-chromen-2-one with the same amine in ethanol or acetonitrile leads to the formation of methylammonium 3-acetyl-5,6,7,8-tetrafluoro-2-oxo-2H-chromen-4-olate, while in dimethyl sulfoxide 5,6,8-trifluoro-7-methylamino-3-(1-methylaminoethylidene)-3,4-dihydro-2H-chromene-2,4-dione is formed. The latter is also formed in the reaction of 5,6,7,8-tetrafluoro-4-hydroxy-3-(1-iminoethyl)-2H-chromen-2-one with methylamine in DMSO, whereas in ethanol and acetonitrile 5,6,7,8-tetrafluoro-3-(1-methylaminoethylidene)-3,4-dihydro-2H-chromene-2,4-dione is obtained. 5,6,7,8-Tetrafluoro-3-(1-methylaminoethylidene)-3,4-dihydro-2H-chromene-2,4-dione reacts with methylamine, yielding 7-mono-or 5,7-bis(methylamino)-substituted derivatives.     

Synthesis of pyridinium salts by the reaction of α, β-unsaturated ketones,primary amines,and compounds with labile hydrogen atoms

The reaction of , -unsaturated ketones or Mannich bases of ketones with primary aromatic amines and ketones (monoketones or dimedone) in the presence of polyhalo-alkanes leads to pyridinium, 5,6,7,8-tetrahydroquinolinium, or sym-octahydroacridinium salts. The reaction of benxalcyclohexanone with primary aromatic amines and malonodinitrile makes it possible to obtain 2-amino-3-cyano-5,6,7,8-tetrahydroquinolinium salts.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1060–1064, August, 1985.     

On the lewis acid catalyzed cyclocondensation of imines with a siloxydiene

A hetero Diels-Alder route to 5,6-dihydro-γ-pyridones is described. Recently, we described the Lewis Acid catalyzed cyclocondensation of aldehydes with siloxydienes to give 5,6-dihydro-γ-pyrones. It was of interest to attempt to extend this reaction to include the imino linkage. Certainly, there have been reports of intermolecular 2 + 4 cycloadditions to “C = N” dienophiles.² However, they have involved particularly activated glyoxyl imines (cf.$\text{1}$,³ acyl imines (via presumed precursor $\text{2}$)⁴ or doubly activated imines (cf.$\text{3}$).⁵ In addition, we note that Weinreb has elegantly exploited intramolecular Diels-Alder reactions of acyl imines⁶ as a new strategem in alkaloid synthesis.     

Reaction of α and γ-methylpyrylium salts with orthoesters

The reaction of orthoesters with α- and γ-methylpyrylium salts gives 2- and 4-alkoxyvinyl-pyrylium salts the acid hydrolysis of which leads to 2- and 4-hydroxyvinylpyrylium salts and the alkaline hydrolysis to pyranylideneacetaldehydes.     

Fluorine-containing 3-arylhydrazono-2,4-dioxobutanoates in reactions with difunctional nucleophiles

3-Arylhydrazono-4-polyfluoroalkyl-2,4-dioxobutanoates reacted with hydrazines to give ethyl 4-aryldiazeno-3-polyfluoroalkyl-1H-pyrazole-5-carboxylates, while analogous reactions of ethyl 3-arylhydrazono-4-pentafluorophenyl-2,4-dioxobutanoates resulted in the formation of 4-aryldiazeno-3-pentafluorophenyl-1,2-dihydropyridazine-5,6-diones or 6-aryl-7,8,9,10-tetrafluoro-2-phenyl-2,4a,6,10b-tetradropyridazo[4,3-c]cinnoline-3,4-diones, depending on the conditions. Cyclocondensation of ethyl 3-arylhydrazono-4-polyfluoroalkyl(or pentafluorophenyl)-2,4-dioxobutanoates with ethylenediamine led to 3-[1-arylhydrazono-2-oxo-2-polyfluoroalkyl(or pentafluorophenyl)ethyl]-5,6-dihydropyrazin-2(1H)-ones, and 3-[1-arylhydrazono-2-oxo-2-polyfluoroalkyl(pentafluorophenyl)ethyl]benzoxazin-2-ones were formed in the condensation with o-aminophenol. Pentafluorophenyl-substituted heterocycles were found to undergo intramolecular ring closure to give 3-hetaryl-substituted 1-aryl-5,6,7,8-tetrafluoro-1,4-dihydrocinnolin-4-ones. The reactions of ethyl 3-arylhydrazono-4-pentafluorophenyl-2,4-dioxobutanoates with o-aminobenzenethiol gave 3-[7-(2-aminophenylsulfanyl)-1-aryl-5,6,8-trifluoro-4-oxo-1,4-dihydrocinnolin-3-yl]benzothiazin-2-ones; 8a-hydroxy-11,12,13,14-tetrafluoro-10-(4-methoxyphenyl)-2,3,4,5,6,7,8a,10-octahydropyrazino[1′,2′:4,5][1,4]diazepino[6,7-c]cinnolin-8-one was isolated in the condensation of ethyl 3-(4-methoxyphenylhydrazono)-4-pentafluorophenyl-2,4-dioxobutanoate with N-(2-aminoethyl)ethane-1,2-diamine.     

A new carotenoid,halocynthiaxanthin from the sea squirt, halocynthiaroretzi

A new carotenoid, halocynthiaxanthin (5,6-epoxy-3,3′-dihydroxy-7′,8′-didehydro-5,6,7,8-tetrahydro-β,β-caroten-8-one) has been isolated from the Japanese sea squirt, $\text{Halocynthia}$ roretzi.     

Tetrahydrochromenylium and -Thiochromenylium Salts from Triketones of the 2-(3-Oxopropyl)cyclohexane-1,3-dione Series

We have worked out the optimal conditions for synthesis of 2,4-diaryl-5-oxo-5,6,7,8-tetrahydrochromenylium and -thiochromenylium salts based on triketones of the 2-(1,3-diaryl-3-oxopropyl)cyclohexane-1,3-dione series. For the first time, along with 5-oxo-substituted salts, we have obtained 5-thioxo-5,6,7,8-tetrahydrothiochromenylium salts. A necessary condition for the formation of the latter on treatment with acids and S-nucleophiles is the presence of electron-donor groups on the aryl substituents of the indicated triketones.     

Superelectrophilic Activation of 8-Hydroxyquinoline in Acid Media and Its Reactions with Weak Nucleophiles

According to the ¹H and ^{1 3}C NMR data, 5-azonia-4-hydroxynaphthalen-1-onium cation, generated by protonation of 8-hydroxyquinoline in the system CF₃SO₃H-SbF₅, reacts with cyclohexane to give diprotonated 5,6,7,8-tetrahydroquinolin-8-one. Further reaction of the latter with cyclohexane yields 5,6,7,8-tetrahydroquinolinium ion. The reaction of 8-hydroxyquinoline with benzene in the presence of aluminum bromide or chloride gives 6-phenyl-5,6,7,8-tetrahydroquinolin-8-one and product of its intramolecular cyclization, 11-hydroxy-6,11-dihydro-6,11-methano-5H-benzo[5,6]cyclohepta[1,2-b]pyridine. The effect of the protonated nitrogen atom on the electrophilicity of dications is discussed.     

Über Pterinchemie. 65 Mitteilung [1]. Herstellung von (6 R,S)-5,6,7,8-Tetrahydro-L-biopterin, 7,8-Dihydro-L-biopterin,L-Sepiapterin,Deoxysepiapterin, (6 R,S)-5,6-Dihydrodeoxysepiapterin und 2′-Deoxybiopterin

Preparation of (6 R, S)-5,6,7,8-tetrahydro-L -biopterine, 7,8-dihydro-L -biopterine, L -sepiapterine, deoxysepiapterine, (6 R, S)-5,6-dihydrodeoxysepiapterine and 2′-deoxybiopterine We describe the preparation of (6 R, S)-5,6,7,8-tetrahydro-L -biopterine (II) by catalytic- (reported in our short communication [2]) and natriumdithionite reduction of L -biopterine (I) and a preparation of 7,8-dihydro-L -biopterine (IV) by treatment of L -biopterine (I) with natriumdithionite. Whereas oxidation of tetrahydrobiopterine II in the presence of oxygen leads to L -sepiapterine (III), dihydrobiopterine IV in acetic acid without oxygen gives deoxysepiapterine (VII), 5,6-dihydro-deoxysepiapterine (VI) and 2′-deoxybiopterine (V) by a disproportionation reaction.     

Aaptanone, a novel zwitterionic metabolite of the aaptamine class with an oxygenated 1,6-naphthyridine core from the Vietnamese marine sponge Aaptos aaptos

A new zwitterionic compound, aaptanone, having a rare oxygenated 1,6-naphthyridine core, has been isolated from the Vietnamese marine sponge Aaptos aaptos, along with the known metabolites, aaptamine, isoaaptamine, and their hydrochloride salts. The structure of aaptanone was determined as 8-methoxy-1-methyl-5,6-dioxo-5,6-dihydro-4H-benzo[de]-1,6-naphthyridine-1-ium-9-olate from spectroscopic data, X-ray analysis, and by spectroscopic analysis of an N-methyl derivative.     

Synthesis of quaternary 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazolium salts

The reaction of dihydroimidazole-2-thiol with N-(3-chloro-2-oxopropyl)phthalimide gave 2-[3-(4,5-dihydroimidazol-2-ylsulfanyl)-2-oxopropyl]-1,3-dioxo-1H-isoindole which underwent intramolecular heterocyclization to dihydroimidazothiazole system by the action of a dehydrating agent. Treatment of 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazole with concentrated hydrochloric acid led to the formation of dihydroimidazo[2,1-b]thiazol-3-ylmethanamine. Water-soluble quaternary 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazolium salts were obtained by alkylation of 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazole with alkyl halides.