Asymmetric reduction of 2,2-dimethyl-6-(2-oxoalkyl/oxoaryl)-1,3-dioxin-4-ones and application to the synthesis of (+)-yashabushitriol

The asymmetric transfer hydrogenation of a series of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones and 2,2-dimethyl-6-(2-oxoaryl)-1,3-dioxin-4-ones was achieved in high enantiomeric excess using a Ru(II) catalyst. The aryl substrates were most compatible with the methodology and this process facilitated a total synthesis of enantiomerically pure (+)-yashabushitriol.     

Preparative synthesis of 2,2-dimethyl-5-(trifluoroacetyl)-1,3-dioxane-4,6-dione (2-trifluoroacetyl Meldrum's acid) and 2,2-dimethyl-6-(trifluoromethyl)-4H-1,3-dioxin-4-one and their synthetic usefulness as (trifluoroacetyl)ketene precursors

A simple and reliable method for the preparation of 2,2-dimethyl-5-(trifluoroacetyl)-1,3-dioxane-4,6-dione and 2,2-dimethyl-6-(trifluoromethyl)-4H-1,3-dioxin-4-one on a multigram scale was developed. These (trifluoroacetyl)ketene precursors were used in the hetero-Diels-Alder reaction with dialkylcyanamides and 1-ethoxyprop-1-yne, as well as in some reactions with nucleophiles.     

Hetero-diels-alder reaction of N-cyanoaniline and pyridinium cyano-(ethoxycarbonyl)methylide with aroylketenes generated in situ in thermolysis of 6-aryl-2,2-dimethyl-1,3-dioxin-4-ones

We have used thermolysis of 6-aryl-2,2-dimethyl-1,3-dioxin-4-ones in the presence of N-cyanoaniline, pyridinium cyano(ethoxycarbonyl)methylide, and 4-hydroxybenzonitrile to obtain the corresponding 6-aryl-2-phenylamino-1,3-oxazin-4-ones, pyridinium ethoxycarbonyl(4-oxo-6-aryl-4H-1,3-oxazin-2-yl)methylides, and p-cyanophenyl esters of 3-aryl-3-oxopropanoic acids. We present the results of a preliminary investigation of the biological activity of these compounds. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 764–768, May, 2006.     

New oxidative cyclizations of 1,3,4,6-tetraketones. Synthesis and structure of (Z)-2-acyl-5-alkyl(aryl)-1,4-dioxaspiro[2.4]hept-5-en-7-ones

Iodosobenzene diacetate oxidation of 1,3,4,6-tetraketones 1a-c yielded (Z)-2-acyl-5-alkyl(aryl)-1,4-dioxa-spiro[2.4]hept-5-en-7-ones (4a-c) in addition to 2-acyl-6-alkyl(aryl)-3-hydroxy-4-pyrones (3a-c). The structure of new spiro-heterocycles 4 was inferred from chemical and spectroscopic data, and the stereochemistry was fully defined by a single-crystal X-ray analysis. Alternative cyclization pathways can be rationalized as proceeding through carbocation intermediates derived from both forms of the ring-chain tautomerism of 1,3,4,6-tetraketones 1.     

6-Aryl-2,2-dimethyl-1,3-dioxin-4-ones: Synthesis and Chemical Characteristics. (Review)

Methods for the production of 6-aryl-2,2-dimethyl-1,3-dioxin-4-ones and their thermolysis in the presence of nucleophiles and dienophiles are discussed     

Five-membered 2,3-dioxo heterocycles: CVI. Acylation of substituted (Z)-2-[1,3,4,4a,5,10b-Hexahydrophenanthridin-6(2H)-ylidene]acetamide with aroylketenes. crystal and molecular structure of substituted N-{(Z)-2-[1,3,4,4a,5,10b-Hexahydrophenanthridin-6(2H)-ylidene]acetyl}acrylamide

Aroylketenes generated by thermolysis of 6-aryl-2,2-dimethyl-4H-1,3-dioxin-4-ones reacted with (Z)-2-[4a,7,10-trimethyl-1,3,4,4a,5,10b-hexahydrophenanthridin-6(2H)-ylidene]acetamide to give (Z)-3-aryl-3-hydroxy-N-{(Z)-2-[4a,7,10-trimethyl-1,3,4,4a,5,10b-hexahydrophenanthridin-6(2H)-ylidene]acetyl}acrylamides whose structure was confirmed by X-ray analysis.     

The synthesis of 5-substituted 3-benzoylamino-6-(2-substituted amino-1-ethenyl)-2H-pyran-2-ones and their transformations into 2H-pyrano[3,2-c]pyridine derivatives

A new approach to the 2H-pyrano[3,2-c]pyridine system is described. 5,6-Disubstituted 3-benzoylamino-2H-pyran-2-ones 3a,b , prepared from the corresponding 1,3-dicarbonyl compounds 1a,b and methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate ( 2 ), were converted into 3-benzoylamino-6-(2-dimethylamino-1-ethenyl)-5-ethoxycarbonyl-2H-pyran-2-one ( 4a ) and 5-acetyl derivative 4b . The exchange of the dimethylamino group in 4a,b with aromatic amines 5a-f,m , héteroaromatic amines 5g-i , and benzylamines 5j-l produced 5-ethoxycarbonyl-3-benzoylamino-6-(2-arylamino- or heteroarylamino-or benzylamino-1-ethenyl)-2H-pyran-2-ones 6a-l , and its 5-acetyl analog 6m . The compounds 6 were cyclized in basic media into 2H-pyrano[3,2-c]pyridine derivatives 7a-h . Analogously react also α-amino acid derivatives 8a-c and 11 as nitrogen nucleophiles producing 9a-c, 10 and 12 .     

A simple synthesis of 4-amino-6-methyl-1,1,1-trifluoro(trichloro)hepta-3,5-dien-2-ones and 2,2-dimethyl-6-trifluoromethyl-2,3-dihydro-4-pyridone

Treatment of 2,2-dimethyl-6-trifluoro(trichloro)methyl-2,3-dihydro-4-pyrones with ammonia gives 4-amino-1,1,1-trifluoro(trichloro)-6-methylhepta-3,5-dien-2-ones. Under similar conditions 1,1,1-trifluoro-2-hydroxy-6-methylhepta-2,5-dien-4-one and 6-chloro-1, 1,1-trifluoro-2-hydroxy-6-methylhept-2-en-4-one cyclize into 2,2-dimethyl-6-trifluoromethyl-2,3-dihydro-4-pyridone. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2263–2265, December, 1997.     

Reaction of 6-aryl-2,2-dimethyl-1,3-dioxin-4-ones with cyanoamino compounds

Aroylketenes have been generated by thermolysis of 6-aryl-2,2-dimethyl-1,3-dioxin-4-ones. They take part in a 1,4-cycloaddition reaction at the CN bond of N-aryl or N,N-dialkyl-N-cyanoamines and of N'-phenyl-N-cyanoguanidine to form the corresponding 2-N-aryl-amino, 2-N,N-dialkylamino, and 2-N-phenylguanidino-6-aryl-1,3-oxazin-4-ones. p-Aminobenzonitrile and cyanoacetamide are acylated by aroylketenes to form the p-cyanophenylamide of p-toluylacetic acid and the cyano-acetamide of benzoylacetic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1265–1268, September, 1989.     

Direct introduction of heterocyclic residues into 1,2,4-triazin-5(2H)ones

3-Aryl-1,2,4-triazin-5(2H)-ones 1a-c react with indoles 2a-c in trifluoroacetic acid/chloroform or in boiling butanol or acetic acid to give 3-aryl-6-(indolyl-3)-1,6-dihydro-1,2,4-triazin-5(2H)-ones 3a-g . Oxidation of the dihydro-1,2,4-triazin-5(2H)-ones 3a-e afforded 6-(indolyl-3)-1,2,4-triazin-5(2H)-ones 4a-e , products of nucleophilic substitution of hydrogen in 1a-c . Refluxing 1b with N-methylpyrrote 5b in butanol for an extended time resulted in the formation of 3-(4-chlorophenyl)-6-(1-meuiylpyrrolyl-2)-1,2,4-triazin-5(2H)-one 4h. The reaction of 1a-c with indoles 2a-c , pyrroles 5a,b , 1,3-dimethyl-2-phenylpyrazol-4-one (8) and aminothiazoles 9a,b in acetic anhydride affords the 1-acetyl-3-aryl-6-hetaryl-1,6-dihydro-1,2,4-triazin-5(2H)-ones 6a-s . Reaction of 1a-c with N-methyl-pyrrole 5b in acetic anhydride gives beside the 1:1 addition products 6h-k also the 2:1 addition products 7a-c .     

Reactions of 2-hydroxybenzonitrile with isocyanates

Triethylamine catalyzes the reaction of 2-hydroxybenzonitrile ( 1 ) with aryl isocyanates to form the corresponding carbamates 2a-c , as well as the cyclization of the latter compounds to either 4[N-(N-arylcarbamoyl)-imino]-3-aryl-2H-1,3-benzoxazin-2-ones 4a-c , or 4-arylamino-2H-1,3-benzoxazin-2-ones 7a-c , depending on the reaction temperature. Under analogous conditions, the carbamates obtained from 1 and 2-chloroethyl isocyanate, 3-chloropropyl isocyanate and ethyl isocyanatoacetate undergo a double cyclization yielding imidazo- and pyrimido[1,2-c|1,3]benzoxazinones 13a,b,17 . Upon heating in phenyl ether, compounds 7a-c , rearrange to 2-(2-hydroxyphenyl)-4(3H)-quinazolinones 10a-c .     

Reaction of 6-aryl-2,2-dimethyl-1,3-dioxin-4-ones with acetylacetone and methyl acylpyruvates

Aroyl ketenes formed in the thermolysis of 6-aryl-2,2-dimethyl-1,3-dioxin-4-ones undergo a [4+2]-cycloaddition reaction with acetylacetone and methyl acylpyruvates to give 2-methyl- and 2-methoxycarbonyl-3-acyl-6-arylpyran-4-ones, respectively.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 161–163, February, 1989.     

Eine überraschende Ringerweiterung von 3-(Dimethylamino)-2,2-dimethyl-2H-azirin zu 4,5-Dihydropyridin-2(3H)-on-Derivaten

An Unexpected Ring Enlargement of 3-(Dimethylamino)-2,2-dimethyl-2H-azirine to 4,5-Dihydropyridin-2(3H)-one Derivatives The reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1a ) and 4,4-disubstituted 2-(trifluoromethyl)-1,3-oxazol-5(4H)-ones 7 in MeCN at 70° afforded 5-(dimethylamino)-3,6-dihydropyrazin-2(1H)-ones 10 (Scheme 4), whereas no reaction could be observed between 1a and 2-allyl-4-phenyl-2-(trifluoromethyl)-1,3-oxazol-5(2H)-one ( 8a ) or 4,4-dibenzyl-2-phenyl-1,3-oxazol-5(4H)-one ( 9 ). The formation of 10 is rationalized by a mechanism via nucleophilic attack of 1a onto 7 . The failure of a reaction with 9 shows that only activated 1,3-oxazol-5(4H)-ones bearing electron-withdrawing substituents do react as electrophiles with 1a . The amino-azirine 1a and 2,4-disubstituted 1,3-oxazol-5(4H)-ones 2b – e in refluxing MeCN undergo a novel ring enlargement to 4,5-dihydropyridin-2(3H)-ones 11 (Scheme 5). Several side products were observed in these reactions. Two different reaction mechanisms for the formation of 11 are proposed: either 1a undergoes a nucleophilic addition onto the open-chain ketene tautomer of 2 (Scheme 6), or 2 reacts as CH-acidic compound (Scheme 7).     

Direct heterocyclization of tetrahydroisoquinolin-1-ylideneacetic acids by the action of 5-arylfuran-2,3-diones

Aroylketenes generated in situ by thermolysis of 6-aryl-2,2-dimethyl-4H-1,3-dioxin-4-ones reacted with 3,3-dialkyl-1-methyl-3,4-dihydroisoquinolines to give (1Z,3Z)-4-aryl-4-hydroxy-1-[3,3-dialkyl-3,4-dihydroisoquinolin-1(2H)-ylidene]but-3-en-4-ones. The crystalline and molecular structure of (1Z,3Z)-4-hydroxy-1-[6,7-dimethoxy-3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene]-4-phenylbut-3-en-2-one was studied by X-ray diffraction.     

Five-membered 2,3-dioxo heterocycles: LXXVIII. Acylation of fischer’s base with aroylketenes. Crystalline and molecular structure of (1E, 3Z)-4-(4-chlorophenyl)-4-hydroxy-1-(1,3,3-trimethyl-2,3-dihydro-1H-indol-2-ylidene)but-3-en-2-one

Aroylketenes generated by thermolysis of 6-aryl-2,2-dimethyl-4H-1,3-dioxin-4-ones reacted with 1,3,3-trimethyl-2-methylidene-1,3-dihydro-2H-indole (Fischer’s base) to produce (1E,3Z)-4-aryl-4-hydroxy-1-(1,3,3-trimethyl-1,3-dihydro-2H-indol-2-ylidene)but-3-en-2-ones. The crystalline and molecular structures of (1E,3Z)-4-(4-chlorophenyl)-4-hydroxy-1-(1,3,3-trimethyl-2,3-dihydro-1H-indol-2-ylidene)but-3-en-2-one were determined by X-ray analysis.     

Synthesis, Structure, and Alkylation of N-Methylmorpholinium 5-[2-Cyanoethyl-1-(4-hydroxy-3-methoxyphenyl)-2-thiocarbamoyl]-2,2-dimethyl-6-oxo-1,3-dioxa-4-cyclohexen-4-olate

N-Methylmorpholinium 5-[2-cyanoethyl-1-(4-hydroxy-3-methoxyphenyl)-2-thiocarbamoyl]-2,2-dimethyl-6-oxo-1,3-dioxa-4-cyclohexen-4-olate was obtained from the reaction of 4-hydroxy-3-methoxybenzaldehyde with cyanothioacetamide and Meldrum's acid in the presence of N-methylmorpholine. The molecular and crystal structure of the title compound have been established and its alkylation has been studied.     

Five-Membered 2,3-Dioxo Heterocycles: XLVI. Reaction of 5-Aryl-4-quinoxalinyl-2,3-dihydrofuran-2,3-diones with Aldehydes and Ketones. Molecular and Crystalline Structure of 5-(3-p-Tolylquinoxalin-2-yl)-4H-1,3-dioxine- 2-spiro-2'-adamantan-4-one

Aroyl(quinoxalinyl)ketenes generated by thermolysis of 5-aryl-4-(3-arylquinoxalin-2-yl)-2,3-di-hydrofuran-2,3-diones act as dienes in [4 + 2]-cycloaddition at the carbonyl group of aldehydes and ketones to afford 2-substituted 6-aryl-5-(3-arylquinoxalin-2-yl)-4H-1,3-dioxin-4-ones. The structure of 5-(3-p-tolylquino-xalin-2-yl)-4H-1,3-dioxine-2-spiro-2'-adamantan-4-one was proved by X-ray analysis.     

Diels-alder reaction of (E)-4-(2-nitroethenyl)-1H-imidazoles and methyl (E)-3-(1-imidazol-4-yl)propenoates

Diels-Alder reaction of methyl (E)-3-(1H-imidazol-4-yl)propenoates 2, 3a-c and (E)4-(2-nitroethenyl)-1H-imidazoles 3d,e with 2,3-dimethyl-1,3-butadiene, cyclopentadiene, and cyclohexa-1,3-diene gave the corresponding cycloadducts 6–9 .     

Novel Stereoselective Synthesis and Molecular and Crystalline Structure of 3-Allyl-4-(4-bromophenyl)-3-cyano-6-oxopiperidine-2-thione

The stereoselective synthesis of 3-allyl-4-(4-bromophenyl)-3-cyano-6-oxopiperidine-2-thione has been carried out by refluxing N-methylmorpholinium 5-[1-(4-bromophenyl)-2-cyano-2-thiocarbamoylethyl]-2,2-dimethyl-1,3-dioxa-6-oxo-4-cyclohexen-4-olate with allyl bromide in ethanol. The structure of the product was confirmed by X-ray investigation.     

Iodocyclization of 2-[allyl(methallyl)sulfanyl]-6-(trifluoromethyl)pyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones

Iodination of 2-[allyl(methallyl)sulfanyl]-6-(trifluoromethyl)pyrimidin-4(3H)-ones was accompanied by cyclization to 2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium triiodides. 3-(Iodomethyl)-3-methyl- 7-oxo-5-(trifluoromethyl)-2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium triiodide was reduced with sodium iodide to 3,3-dimethyl-7-oxo-5-(trifluoromethyl)-2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium iodide.